Where cures begin.

Salk Institute 08 | 14

THE SALK INSTITUTE COMMEMORATESWhere cures begin.

Salk Institute 08 | 14

THE SALK INSTITUTE COMMEMORATES

“

HOPE LIES IN DREAMS, IN
IMAGINATION AND IN THE”

COURAGE OF THOSE WHO
DARE TO MAKE DREAMSINTO REALITY.

				

August 2014

Inside Salk

William Brody, MD, PhD
President
Marsha Chandler, PhD
Executive Vice President
Rebecca Newman
Vice President,
External Relations
Anna-Marie Rooney
Chief Communications Officer
Christopher Emery
Director of Scientific Communications
and Media Relations
Kristina Grifantini
Science Writer
Sarah Lifton
Staff Writer
Liz Hincks
Web Editor

1216One-on-one with…Nicola Allen

Next generation: Amy Firth

3 EXECUTIVE MESSAGE

32 Education Outreach launches innovative programs
to promote science education

L E A D S T O RY

4 The Legacy of Jonas Salk

Salk scientist Vicki Lundblad wins accolades
INSTITUTE NEWS12 One on one with…Nicola Allen
16 Next generation: Amy Firth
20 Bestselling food writer Michael Pollan makes
exclusive appearance at the Salk

21 Second annual Step into Discovery brings
the community to the Salk

22 Backward glances at Back to Basics lecture
Salk microflora researcher Janelle Ayres named
Searle Scholar

John McDonagh
Web Developer

23 San Diego developer Donald Cohn elected to

Joe Belcovson
Photographer

24 Spectacular first season of Salk Science & Music Series

Jon Labes
Video Manager
Melanie Norton
Media Relations Manager
Máximo Escobedo
Senior Designer
Melissa Figueroa
Graphic Designer

Salk Board of Trustees

concludes; lineup announced for next year

26 Scientific symposia mark milestone birthdays forRonald Evans and Geoffrey Wahl

D I S C O V E RY R O U N D U P

35 New stem cell research points to early indicatorsof schizophrenia

36 Genes discovered linking circadian clock witheating schedule

37 Discovery reveals circuitry of fundamental
motor circuit

38 Salk scientists identify novel regulator of
key gene expression in cancer

39 Researchers identify new cause of brain bleeding
immediately after stroke

40 Explaining how memories stick together
41 Salk lab turns skin cells into human airway tissue
PHILANTHROPY NEWS42 Glenn Center for Aging Research receives
additional $3 million from the Glenn Foundation
for Medical Research

28 Salk Women & Science continues to gain momentum

43 Salk Institute receives $25 million gift from former

29 Foundation leaders brush up on tax laws and foundation

44 Salk science leads to discoveries

management at the 42nd annual Tax Seminar forPrivate Foundations

Visit the Salk Institute at www.salk.edu

30 Geoffrey Wahl elected to Academy of Arts and Sciences

Inside Salk is printed on recycled paper.

Class of 2014 for outstanding scientific work

Inside Salk is published by the
Salk Institute for Biological Studies.
We welcome your input. Please sendcomments to communications@salk.edu
or contact the communications department
at 858.453.4100 x1371.

34 Jared Diamond visits the Salk

31 Two faculty inducted into the 2014 elected class of
fellows of the American Association for Cancer
Research Academy
Cancer metabolism expert Reuben Shaw promoted
to full professor

Salk trustee Conrad T. Prebys

45 I N S I D E R ’ S V I E W
CALENDAR

Back CoverDear Friends,
ONE HUNDRED YEARS AGO, ON OCTOBER 28, A CHILD WAS BORN
in New York City. Bright and precocious, he rose from humble origins toenter college at age 15, and then enrolled in medical school. But along
the way, he decided he’d rather help humankind more broadly and opted
to become a medical researcher instead of a physician. By 1955, he hadachieved his goal, discovering the polio vaccine and changing the courseof history. Jonas Salk—for of course that’s who I’m talking about—haddefeated a disease that had struck dread into the hearts of people
worldwide for over a century.
At that point, Salk could easily have rested on his laurels. But uponreceiving the Congressional Medal for Distinguished Civilian Achievementin 1956, he said, “I feel that the greatest reward for doing is the opportunity to do more.” And do more he did: in 1960, he established theresearch institute that bears his name.
This issue of Inside Salk celebrates the centenary of Jonas Salk’sbirth and his extraordinary legacy as a scientist and a visionary. Although
he died nearly two decades ago, his spirit remains vibrant here at the
Salk Institute, where his commitment to breaking down barriers of all
kinds is deeply embedded in our culture. The following pages are as
much a reflection of Salk and his values as they are of the remarkable
men and women whose careers and discoveries have been fostered atthe “temple of science” he founded.
In addition to our cover story on Salk’s legacy at the Institute, thisissue introduces one of our newest faculty members, Nicola Allen, as
well as a rising young star, postdoctoral researcher Amy Firth. We marksome milestones for our faculty, including the 65th birthdays of two
accomplished scientists, plus promotions, awards and special events.
Jonas Salk was deeply committed to nurturing future generations ofWilliam Brody

scientists, which makes it especially apt that we are highlighting two
brand new initiatives of our Education Outreach program. And our
Discovery Roundup section features several recent findings by our facultythat have generated new insights in fields ranging from circadian rhythms
to schizophrenia, from lung disease to memory storage, and from cancer
to motor circuitry.
I hope you’ll enjoy reading our retrospective on Salk and the latest
news issuing from his creation. It is both an honor and a responsibility
to steward his vision—a role that all of us at the Salk Institute enthusiastically embrace. As a friend and supporter of the Institute, you too sharein Jonas Salk’s vision and the scientific successes that vision has madepossible. We are all most grateful.

William R. Brody, MD, PhD
President, Salk Institute
Irwin Jacobs Presidential Chair

PANTONE
871 C
Metallic Gold
Spot Color

Where cures begin.

Salk Institute 08 | 14

THE SALK INSTITUTE COMMEMORATESON THE COVER
This issue commemorates the 100th anniversary of founder Jonas Salk’s birthday.
Cover art based on a 1956 photo of Jonas Salk taken by Yousuf Karsh. Courtesy of the Estate of Yousuf Karsh.
Inside Salk February 2011www.salk.edu

www.salk.edu
Inside Salk 8 | 14 Executive
Message53

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www.salk.edu

The Legacy ofJonas Salk
100 years after Jonas Salk was born, his life is still changing the world.
ON OCTOBER 28, 1994, THE STAFF OF THE SALK INSTITUTE FOR BIOLOGICAL STUDIES
gathered in the windy courtyard to celebrate what would be the 80-year-old founder’s last birthday.
After his friends and colleagues had taken turns speaking to the assemblage, Jonas Salk, oneof the most famous scientists in history, took the podium. Salk surveyed the attendees: staff
and scientific luminaries, including several Nobel laureates, who had joined in his dream ofcollaborating across scientific boundaries to solve the world’s problems.
“I express my gratitude for the opportunity I had to provide you with the opportunity to bringout the best in yourselves,” said Salk, draped in a giant lei, a birthday gift from the chair of theInstitute’s board. “This is what the Institute was intended for.”It must have been a gratifying moment. Not only had Salk developed the first successful polio
vaccine, making history by conquering one of the world’s most terrifying diseases, he’d also
lived to see the Institute, which he called his “experiment,” grow into a research facility withan international reputation for cutting-edge biological work.
Heart failure led to Salk’s death the following June. His influence on the world did not end
then, however. Salk, who made Time magazine’s list of the 100 most influential people of the20th century, saved countless lives through the polio vaccine. And through the Salk Institute,
he is still enabling some of the world’s greatest thinkers to make life-changing discoveries.
Looking back, it is hard to pinpoint precisely what it was about Jonas Salk that led him to suchtremendous success, not once, but twice. The recollections of those who knew the man—aphilosophical, confident and soft-spoken scientist who eschewed publicity while relentlessly
tackling global health issues—demonstrate a lasting legacy and positive influence on the future.

www.salk.edu

Inside Salk 8 | 14 Lead Story

5

A SMALL INSTITUTE, DREAMING BIG» View video: www.salk.edu/JonasSalk100/

How do you top coming up with the world’s
first effective polio vaccine? For many
scientists, that would have been a sufficient,career-culminating event. But not for Jonas
Salk. After his work on the vaccine, he wasdetermined to fight other global health threats.
The best way to do that, he reasoned, was tobring together thinkers from across fields ofstudy in a space that supported scientificcreativity—a space that didn’t just provide
laboratory equipment, but encouraged crossdisciplinary breakthroughs, too.
In 1960, Salk achieved the beginnings of
his second legacy: he formally founded an
ambitious, multidisciplinary institute in what
was then a little-known area of San Diego,
California. He envisioned establishing what
he called a “crucible of creativity” that would
encourage collaboration over competition,
mutual appreciation over siloed departments,
and a pervasive sense that everyone’s work, in
however small a way, contributed to bettering
the human condition. To manifest this vision,
he worked with famed architect Louis Kahn
to design a space that reflected these ideals
while recruiting some of the best minds in avariety of disciplines, including future Nobel
Prize winners Francis Crick, Renato Dulbecco
and Jacques Monod.
“He was not at all afraid to populate theInstitute with scientists famous in their own
right,” says Greg Lemke, a professor in the
Molecular Neurobiology Laboratory, whose
accomplishments have led to a greater
understanding of the immune and nervous
systems. “There’s a real danger for people
with his level of fame to surround themselveswith acolytes. Instead, he recognized that
if you gather the brightest minds and givethem a place to collaborate, new scientificfindings would emerge. That is how he built
a successful institute.”
In her book, Genesis of the Salk Institute,professor emeritus Suzanne Bourgeois reflects
on how Salk’s vision attracted and inspired an

impressive generation of scientific minds. Andeven when the Institute was securing funding
in the early days, it “had assets more valuable
than money: a reputation of distinction, a greatbuilding, and many loyal employees, both faculty
and support staff, for whom the Salk Institutewas not just a job, it was a dream,” she wrote(pg. 180).*
Salk conveyed this dream not just throughthe conviction of his scientific endeavors, butalso through a faith in intuition and an appetite
for risk-taking, something he instilled in theInstitute’s culture. He inspired his colleagues
to trust their guts, in both science and life,
a philosophy that permeated many of his
interactions at the Institute.
“The only advice I ever followed I got fromJonas: ‘Do what makes your heart leap,’” says
Bourgeois, who, along with future husband
and founding fellow Melvin Cohn, now also a
professor emeritus, were early recruits to theInstitute. At Salk, Bourgeois accomplishedpioneering work on the regulation of gene
expression, while Cohn carried out seminal
studies of the body’s immune response.
During his four decades at the Institute,
Inder Verma, professor of genetics and oneof the world’s leading authorities on genetherapy, says that he received three pieces ofadvice from Jonas Salk that he has carried withhim ever since. In addressing the entire faculty,
Salk counseled them to be “good ancestors.”
To new faculty, he specifically called upon themto do what was good for the Institute. And toVerma himself, when Verma had lamented thelack of credit for a service he provided, Salk
advised him to remember that the reward ofwork well done is to be asked to do it again.
“These became three of my defining guideposts,” says Verma, holder of the Irwin and
Joan Jacobs Chair in Exemplary Life Science.
Salk illustrated this last piece of advice one
day when Verma bumped into him in theInstitute’s courtyard. The visibly excited Salk
said that he had just met an old acquaintance
who had brought along a teenage grandson.

*Bourgeois, Suzanne. Genesis of the Salk Institute. Oakland: University of California Press, 2013

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www.salk.edu

From left, clockwise:Francis Crick, Edwin Lennox,
Jacques Monod, Jonas Salk,
Leslie Orgel, Melvin Cohn,
Salvador Luria, Jacob Bronowski,
Renato Dulbecco (1966)

www.salk.edu

Inside Salk 8 | 14 Lead Story

7

When introduced to the man who conquered
polio, the boy nonchalantly asked what polio
was. The disease had been controlled so
thoroughly in the country that the grandson had
never heard of it, which Salk considered to be
the ultimate triumph. “This is one of Jonas’ gifts
to me: a demonstration that reward is in theoutcome, not the gratification of recognition,”says Verma.
LOWERING WALLS ACROSS DISCIPLINES
Jonas Salk was particularly invested in the ideaof lowering walls—literal and metaphorical—
between fields of study, with a focus on bringing
together the arts and sciences. The institute hedesigned with Kahn embodied this philosophy:
not only is it visited by tourists from acrossthe globe for its remarkable design, but its
central open courtyard and unique absenceof dividing walls between labs foster dailycollaboration and interaction among scientists.
Within this structure, the Institute bridges
disciplines of molecular, cellular, systems,
behavioral and computational biology acrossa range of disease areas. Collaborations
between Salk scientists are a direct result of
the Institute’s unique culture and physicalstructure, according to director of the Salk
Institute Cancer Center Tony Hunter, whose
groundbreaking research has led to newleukemia treatments. “To be successful, we
have to collaborate and be greater than thesum of our parts,” says Hunter, holder of theRenato Dulbecco Chair. “I believe that’s how
we’ve been able to achieve so much despite
being a small institute.”
It was crucial to work with people who had
different interests and areas of expertise, in
Salk’s view. Some of Salk’s early appointmentsemphasized his push for interdisciplinary efforts,

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including his decision to bring in faculty whoweren’t typical biologists, such as Salk Founding
Fellow, mathematician and poet Jacob Bronowski
and, in 1970, junior faculty member Ursula
Bellugi, who later became a world-renowned
expert on signed languages.
“He said to me, ‘I love your research because
it reveals how nature creates defects and thehuman mind overcomes them,’” says Bellugi,
who is now director of the Laboratory for
Cognitive Neuroscience.
Bellugi recalls that Salk frequently stopped
by the lab to chat with study participants andtheir families. With his support, Bellugi and her
lab eventually bridged linguistics and molecularstudies to develop breakthrough insights into
the neurobiological basis of language and a
genetic condition known as Williams Syndrome.
Even today, despite not having a formal
humanities program, the Institute is known for
its deep appreciation of the arts. Every year, it
hosts talks by renowned authors (most recently
Jared Diamond and Michael Pollan), a classical music series and symphony concerts in the
courtyard. Recent exhibitions by leading artists
include the works of glass sculptor Dale Chihuly
and painter—and Salk widow—Françoise Gilot.
Salk’s ideas about breaking down the boundaries between labs extended to how an individual
scientist defined his or her field of research. Salk
professor Fred Gage, whose work has led to anabundance of critical new knowledge in genetics
and neuroscience, says Salk promoted the ideathat scientists should be able to go deep into
an area of research but also be able to turn andmove in a completely different direction without
being constrained.
“This freedom,” says Gage, holder of the
Vi and John Adler Chair for Research on AgeRelated Neurodegenerative Disease, “hasallowed many very successful scientists topursue multiple scientific directions in theircareers at the Salk Institute. You can’t do thatin many places.”
A RELUCTANT ICONOCLAST
Jonas Salk never intended to be an iconoclast
says his youngest son, Jonathan Salk, a
psychiatrist based in Los Angeles. But when
Jonas Salk believed something to be true—
through a combination of logic and instinct—
he followed it through to the end. His restless,unyielding drive led him not only to develop an
inactivated virus vaccine for polio when others
insisted it couldn’t be done, but to found an
institution that approached creativity in sciencefrom a multidisciplinary focus, a tactic increasingly common in research institutes today but
fairly unusual at the time.
In the lab, Salk’s approach was similarly
unconventional as he explored promisingconcepts. Eldest son Peter Salk, a physician
who worked with his father on cancer, multiple
sclerosis and AIDS vaccine research, recalledthat Jonas Salk would come into the lab on
occasion with a new idea that would turn things“topsy turvy.” This ability to look at things froma new angle also led him to create clear representations of complex data, which he called“making the invisible visible,” says Peter Salk.
Jonas Salk often walked the halls to think
and, during one walk, he told Ronald Evans,
director of the Institute’s Gene Expression
Laboratory, that risks pay off in science as wellas in life, a truism easy to say but one that
Salk demonstrated in his two greatest legacies.
“Jonas was a visionary who was not only brilliant
but thought differently,” says Evans, holderof the March of Dimes Chair in Molecular andDevelopmental Biology and a Howard Hughes
Medical Institute investigator whose innovativewww.salk.edu

www.salk.edu

Inside Salk 8 | 14 Lead Story

9

Peter Salk speaks about his father’s legacy at a Salk Institute educational event.

A Legacy Beyond Science
AFTER DEVELOPING THE POLIO VACCINE, JONAS SALK HAD AN AMBITIOUS
vision to bridge science and the humanities to solve major world problems.
Now, this aspect of his vision is the Jonas Salk Legacy Foundation’s focus
as part of an effort to address global issues through public health, policy andsocial lenses.
A prolific author as well as a world-renowned scientist, Salk set forth his
ideas in books, articles and lectures that explored the human dimension
underlying global problems—such as overpopulation—and suggested a wayof thinking that might help solutions emerge. In his writings and his personal
interactions, he encouraged a cautious optimism and faith in the power ofcreativity and collaboration across disciplines to tackle the broad array ofchallenges confronting humanity.
“Creating a polio vaccine and establishing the Salk Institute were enormous
accomplishments,” says Salk’s eldest son, Peter, the Legacy Foundation’spresident. “My hope is that this foundation will complement the Institute andhelp bring the fullness of my father’s dreams to fruition.”
The foundation is helping to organize a series of conferences, symposia
and public events around the globe to celebrate Jonas Salk’s centennial period.
(See www.jslf.org for further information.) Other foundation efforts include
archiving and making publicly available historic lab materials; collaboratingwith the Mandeville Special Collections at the University of California, San
Diego Library to facilitate online access to Jonas Salk’s papers; supporting theworldwide eradication of polio; and promoting collaborative programs to tackle arange of public health and societal issues.
“One of my father’s guiding principles was the notion that our capacity as
human beings to think and act creatively gives us the ability to make the world
a better place,” says Salk’s youngest son, Jonathan. “He had a passion for life,a joy in his work and a vision for a better future that I hope will be carried forward
through this foundation.”

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Lead Story Inside Salk 8 | 14

work on hormones has led to more than half adozen drugs for cancer and other diseases.
Salk also urged other scientists to take risks
when their instincts prompted them to do so.
For instance, he once asked Greg Lemke whether
Lemke was a mutant. The two had been talking
about an experiment involving mutant mice, andLemke thought Salk was asking him about themice. But in fact, Salk was using the term to
distinguish between “evolvers” and “maintainers” of the status quo.
“There were things that became clear as
Jonas explained this,” said Lemke, who holds
the Françoise Gilot-Salk Chair. “First, that Jonasconsidered himself as a mutant, and second,that he wanted this Institute to be populated
by mutants. My answer today would be: I hope
I am a mutant.”
Like any public figure—particularly one who
was a nonconformist—Salk had his disappointments. An intensely private man, he was not
comfortable in the limelight, and the constant
media attention aroused resentment from somein the scientific community. Salk was neverinducted into the National Academy of Sciences,
nor did he receive the Nobel Prize, a decisionthat some still say was unfortunate. Nevertheless, Salk seemed to take it in stride, an example
of good faith for his colleagues.
“I often said to him that he should havereceived the Nobel Prize,” says Distinguished
Salk Professor Roger Guillemin, Nobel laureate,
who joined the Institute in 1970. “He’d smileand say, ‘Everyone thinks I did, so it makes
no difference.’”
BEYOND THE LAB
In addition to encouraging innovations inscience, Salk also saw the Institute as an
incubator for the next generation of trailblazers
in their fields. Even though it was never adegree-granting center, more than 3,200
postdoctoral fellows and graduate students
have trained within its walls, and several havegone on to win Nobel prizes.
“Jonas saw the Salk Institute as an artists’colony for scientists, and the people who learn
their trade here carry that ethos and creative
inclination with them,” says William Brody,
president of the Institute. “When young
scientists are exposed to our great thinkers
and dynamic intellectual environment, it
alters their perspective on what’s possible.”www.salk.edu

“Jonas was a visionary who was not
only brilliant but thought differently.
– RONALD EVANS

But it wasn’t only scientists that Salk
wanted to educate. Passing on knowledge tothe public—especially the younger generations—to help them be “good ancestors” was especially
important to him, maybe in part because hehad seen the power of an educated public during
the March of Dimes campaign to fundraise fordevelopment and testing of his polio vaccine,leading to its quick and widespread use.
Molly Hart Lebherz met Salk in the early
1990s at a group discussion on peace advocacy
when she was working as a science education activist at what would later become theFoundation for Global Community. At first, she
was star struck at meeting the person who hadbanished the “dark cloud” of fear of polio that
she recalled from her childhood, but his kinddemeanor soon put her at ease. Through theirfriendship, the Institute helped the foundationwww.salk.edu”

distribute the 1972 photo of Earth taken on the
Apollo 17 mission to classrooms to serve as avisual teaching tool on conservation. Salk, shesaid, loved the idea and called the image the“best reference material.”“He thought that there was nothing more
important than impacting the next generation
with a positive point of view. He wanted me toconvey to them that humanity makes mistakes,
but we can fix them,” Lebherz says, addingthat she, professor emeritus Walter Eckhart
and Salk often gathered, sometimes as
frequently as once a month, to brainstorm
new ways to reach students. “He asked me tostress to the children that their minds werethe most important laboratory.”
Today, the Institute continues to communicate the importance of science outside thelab through four different elementary and highschool science outreach programs. Each year,
Salk’s Education Outreach program reaches
about 3,000 middle and high school students
in San Diego County with programs designed
to inspire them to pursue studies and careersin science.
These outreach efforts are just one of themany ways Jonas Salk’s life continues to havean immeasurable impact on the world 100 years
after he was born. His commitment to leave
the world a better place drove his philosophicaloptimism, an optimism that inspired the people
he knew and that is woven into the fabric of theinstitute he built.
“I took to heart an idea from Jonas that you
get what you focus upon,” says Eckhart. “For
Jonas, I think his goal was always for science todo something helpful for humanity.”

Inside Salk 8 | 14 Lead Story

11

One on one with…

Nicola Allen
Nicola Allen is a neuroscientist, but she doesn’t focus on the
superstar of the brain, the neuron. Rather, she studies astrocytes,
star-shaped cells once thought to be “filler,” but recently shown tobe crucial to brain function—the producer, director, stage designerand supporting cast to the neurons.
These mysterious brain cells have only recently edged into the field of
neurobiology as a viable research area and they have significant potential for
helping to understand neurodevelopmental and degenerative diseases like autism,
epilepsy, schizophrenia, stroke and Alzheimer’s disease. These prolific cells are,Allen says, a major player in the brain, despite their longtime obscurity.
Named for their multi-armed shapes—where long branches extend from a single
cell body to touch over 100,000 neural connections known as synapses—astrocytes
do more than provide the support system and scaffolding for the brain. Whilethe bushy astrocytes don’t transmit electrical signals of their own, they use
chemical signaling to affect nearby neurons, setting the stage for complex neural
messaging. And, like neurons, astrocytes exist in a variety of forms found indifferent configurations throughout animals’ brains, increasing in number roughly
proportional to the brain’s size.

To better untangle the role of these enigmatic cells, Allen’s lab
investigates astrocyte protein families that appear to be crucial
in neural development, operation and adaptation.

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One-on-One Inside Salk 8 | 14

Astrocytes, shown above, surround neurons
and assist with nerve growth and function.

www.salk.edu

www.salk.edu

Inside Salk 8 | 14 One-on-One

13

From left to right: Catriona Lewis, Isabella Farhy, Matthew Boisvert, Nicola Allen, Tongfei Liu, Cari Dowling

What drew you to start researching the brain?
Growing up, my all-girls’ grammar school in England had great biology
classes and teachers. I thought I’d be a vet or a doctor, but I realizedthat fundamental research drew me the most because you’re findingout what’s really going on, whereas in medicine, you’re at the end
phase of new discoveries. The brain is the most mysterious of all theorgans, so I wanted to learn more.
I was the first in my immediate family to receive a PhD, which
focused on the cellular mechanisms that go wrong during stroke.
Neurodegenerative diseases interested me the most because they
are so enigmatic. My mom’s always telling me to hurry up and cure
Alzheimer’s—hopefully, our findings will help lead to that someday.

Why are astrocytes overlooked in conventional
neurobiology?
Cell types like astrocytes are understudied even though they have huge
implications for quality of life and aging. Traditionally, researchers thoughtthat studying neurons would tell us what we need to know about thebrain because they are the cells that are sending electric signals, making
decisions and relaying messages. Now, we think that astrocytes are justas useful to study—not only do they make up about 50 percent of the brain,
but they are actively instructing the neurons on how to connect with eachother as the brain develops. And in adult brains, astrocytes are modulating
ongoing neuronal activity, which will completely change the output of theneurons. Astrocytes are involved in every stage of development and likely
have different roles as one ages, so they are incredibly important.

What are the implications for astrocytes in disease?
Other researchers have done experiments in the last few years showing
that, in mice with genetic predispositions to developmental disordersthat model autism, the introduction of astrocytes actually rescues thedefective neurons. New astrocytes don’t completely cure the mice,but their presence increased the growth of neurons’ branched projections
and alleviated a lot of symptoms, such as breathing difficulties.
Similarly, introducing mutant astrocytes to normal neurons is enoughto make the neurons defective. So there is this real, constant interaction
between cell types that is setting up the right connections in the brain
and the number of connections.

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So could a better understanding of astrocytes leadto “new and improved” brains?
The long-term goal of studying astrocytes is to learn how to repair
damaged circuits by prompting neurons to reform synapses in a controlled
way. By reintroducing astrocyte factors to a damaged brain, you could,
in theory, encourage neurons to create new connections and improvebrain function.
Previous work showed that bringing astrocytes from young animals
into old animals gave the old animals a new plasticity in the brain—that is, they were more easily able to make connections that improve
cognition—while bringing in old astrocytes had no effect. Studies donein 2013 found that introducing human astrocytes into mice resulted in
an enhanced ability in behavioral learning in the mice, potentiallybecause the larger, human astrocytes could interface with more synapses.
We want to understand these special features of young astrocytes thatenable the brain to be flexible and create new connections. However, in
eventual therapeutic applications, you wouldn’t want to introduce toomuch plasticity, or the brain would forget everything it learned instantly.
We want to manipulate those features in a controlled way.

What are the big questions your relatively new lab
at the Salk Institute aims to tackle?
Astrocytes secrete many proteins that affect synapses. Before I began
my research, it was already known that one class of proteins theastrocytes secrete establishes normally structured synapses between
www.salk.edu

» View video: www.salk.edu/allen

neurons. However, those synapses were silent—they didn’t have any
electrical activity. I discovered a second class of proteins that is
responsible for affecting the ability of the neuron to respond toneurotransmitters and communicate with its neighbors. This isn’t
the whole story—this class only establishes an immature connection
between neurons—so we are looking for an additional class of proteinsthat strengthens synapses later in mature brains. We also know thatastrocytes secrete classes of proteins that make inhibitory connections
between neurons, but we don’t know what these proteins are yet.

There are a lot of myths about the brain. Which, asa neurobiologist, would you most like to dispel?
The myth that we only use 10 or 20 percent of our brains still persists
in culture even though it’s been discredited. In truth, nearly all of ourbrain areas are active at some time over a given day.

What advice do you convey to new scientists?
I think the most important thing for a scientist is a sense of perseverance
and, along with that, a positive attitude. Also, being open to new ideas
is crucial. Even though science is about being inquisitive, sometimes
it’s easy to get stuck in one way of thinking. Scientists should bereceptive to new ideas, able to look at findings and follow up acrossdisciplines if needed.
www.salk.edu

That is what’s great about the Salk Institute. I believe very strongly
in the mission of the Institute in that we’re doing research to understandbasic biology, but in the long term this research will likely have atangible effect for people. So much of what we study has the strong
potential for therapy. Having the flexibility to follow questions anddevelop collaborations will help us reach that knowledge faster.

What would people be most surprised to find out
about you?
I spent six months traveling before doing my PhD, backpacking throughFiji, New Zealand, Australia, Indonesia, Singapore, Malaysia andThailand. While in New Zealand, I went skydiving, which was fantastic.
After that I did another backpacking trip with my brother to Vietnam andChina for two months. I’ve been scuba diving in Malaysia, Thailand andVietnam. Next, I’d love to go to the Galápagos Islands.

What do you do in the little free time you have
between setting up a lab and research?
My boyfriend and I kayak, snorkel, watch wildlife and frequently visit
the San Diego Zoo. If I really need a break, I watch British crime series,
particularly PBS Masterpiece Mystery: Inspector Lewis, Prime Suspect,
Sherlock and others.

Inside Salk 8 | 14 One-on-One

15

Nextgeneration:

Amy Firth

16

Next Generation Inside Salk 8 | 14

www.salk.edu

A

Amy Firth tests the limits in thelab and on the playing field.
AMY FIRTH DOESN’T BELIEVE IN LEAVING WELL
enough alone. She has an affinity for demanding
sports—she’s competed in two Ironman triathlons anda 50-kilometer trail run, and she trained for the six-day
TransRockies Run that took place earlier this month, a
120-mile trail race through the mountains of Colorado.
And that’s not to mention the high-level horse competitions that were her passion when she was younger.
“I always like to test how far I can push myself,”says Firth, a postdoctoral researcher in the lab of Salk
professor Inder Verma. “Once I’ve done one thing, I
have to go to the next level and do the next crazy thing.”
She could just as easily be describing her career inscience, which has taken several twists and turns on its
upward trajectory. Firth, who grew up on a farm in Yorkshire, England, was always interested in science because
she loved animals and wanted to become a veterinarian.

www.salk.edu

Inside Salk 8 | 14 Next Generation17» View video: www.salk.edu/firth

But she soon realized that in order to treat her
patients, she would need to have an understandingof drugs and how they worked. So when she got to
the University of Bath, she focused instead on pharmacology—the study of drug interactions with the body.
It was during her final year of college, as part of athree-month capstone project, that the course of her
career changed yet again. Landing in the lab of Sergey
Smirnov, she learned to record currents across cells
that were isolated from the pulmonary artery.
“And that,” she says, “was the start of my interestin lungs.”
Firth remained at the University of Bath to earn
her PhD, and when it came time for her to find a
postdoctoral position, she was keen for a placement
in a world-renowned lab studying pulmonary hypertension. She ended up at University of California, San
Diego, working with Jason Yuan, who was studying ion
channels and pulmonary disease pathogenesis. “It wasa good transition forward to continue what I was doing
and apply it to disease pathogenesis,” she says.
UC San Diego, renowned for its clinical programin chronic thromboembolic pulmonary hypertension (CTEPH), provided Firth with unique access tosurgically removed lung tissues. Usually blood clots
in the lungs, or pulmonary embolisms, resolve without
treatment or are broken up through medication. Whena clot doesn’t dissipate, or clots recur frequently,

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Next Generation Inside Salk 8 | 14

however, harmful vascular changes can take placein the lungs and can result in pulmonary hypertension. Pulmonary hypertension is associated with highmorbidity and mortality due to right-sided heart failure.
Although rare, CTEPH is often misdiagnosed because
its symptoms can be similar to those of more common
conditions, and it may occur in patients with no overt
history of pulmonary embolism.
In studying how blood clots in CTEPH become
fibrotic and solid, completely blocking the lungs,
Firth began to look at what cell types contribute to
the condition. What she found was that cells capableof developing into multiple types of tissues seemed
to be involved in the progression of the disease.
And from there, her research began to focus onstem cells. Since joining Verma’s lab four years ago forher second postdoctoral appointment, Firth has beenmodeling the respiratory tract—specifically, airways.
Taking skin cells from patients with lung disease,she has reprogrammed the cells to become induced
pluripotent stem cells (iPSCs), then coaxed them tobecome lung cells in order to study them in a dish. Her
method circumvents some of the limitations inherent
in existing methods of studying lung disease. Mice,for instance, develop lung disease very differently
from humans and don’t manifest it to the same extent,
which makes translating information from mousemodels to humans difficult. And human lung tissue

This image shows induced pluripotent stem cells
that have been coaxed to change into epithelial
cells which line the airways of the lung. The blue
stain indicates the cells’ nuclei. Clusters of basal
bodies (red) enable the cells to generate hundredsof hair-like projections called cilia (light blue).
These ciliated cells beat to propel mucus out of the
airways and protect from infection.

www.salk.edu

Amy Firth competing in her first 3-day horse trials event in 1996,
pictured here during the cross country jumping portion with her horse,“The Nightwatchman.”“

Amy is fearless,exciting anddemands the bestfrom herself andher colleagues.
I can always
count on her”

to deliver.

– INDER VERMA

www.salk.edu

is especially perishable, providing only a brief window
before starting to deteriorate.
“I wanted to find a way to study human disease in a
reproducible way, and having iPSCs basically gave me apool of cells with the capacity for indefinite growth andgeneration of any cell in the body,” she explains.
Once she has guided the iPSCs into becoming lungcells, Firth can use gene editing techniques to remove
a mutated gene and replace it with a corrected one. Or,
conversely, if donated patient tissue is unavailable, she
can remove a normal gene and insert a mutation.
“It gives us a reproducible way of looking at therole of mutations in disease and looking at what thedownstream signaling pathways are that occur after you
have a mutation,” she says. “The nice thing about thesystem is that with little tweaks here and there, I canessentially use it to model nearly any lung disease, andI can take this wherever I want.”
Her research was published in March in theprestigious Proceedings of the National Academyof Sciences. But Firth is quick to caution that her
technique is still in the early stages and needs somerefinement. She’s hoping it can eventually be used
for high-throughput screening to identify new drugs,
as well as to uncover the underlying mechanisms fordiseases where the mechanisms aren’t well known.

“Everyone asks me if I’m trying to regenerate a lungin a dish,” she says, “but I think being able to put cells
back and remodel a lung is a ways off.” That said, she’s
begun forging collaborations with other scientists, using
the cells she generates to begin exploring that possibility. Her expertise in lung stem cells also led to an
invitation last year to edit a book on the subject, whichis slated for publication this fall.
“Amy is fearless, exacting and demands the bestfrom herself and her colleagues,” says Verma, whoholds the Irwin and Joan Jacobs Chair in Exemplary
Life Science. “I can always count on her to deliver.”
As if all this isn’t demanding enough, Firth continues to test the limits outside the lab, as a Category
2 bicycle racer for the South Bay Wheelmen in Los
Angeles, as well as racing for the Rehab United Elite
triathlon team in San Diego. Her biggest extracurricularchallenge may lie ahead, however. She recently joined
her lab’s softball team, which has left this diehard fanof Britain’s Tottenham Hotspur soccer team a bit out ofher element but game to learn.
“They were having so much fun, I decided to join
them,” she says. So every Monday, she dons a baseball
glove and takes her place behind the infield, ready forwhatever the players, science and life bat her way.

Inside Salk 8 | 14 Next Generation

19

BESTSELLING FOOD WRITERMICHAEL POLLAN
MAKES EXCLUSIVE APPEARANCE AT THE SALKNEW YORK TIMES BESTSELLING AUTHOR
and journalist Michael Pollan paid a visit
to La Jolla on March 19 to take part in athought-provoking discussion at Salk. Pollan
is the author of the bestsellers In Defenseof Food: An Eater’s Manifesto and The
Omnivore’s Dilemma: A Natural History ofFour Meals, which was named one of theten best books of 2006 by the New YorkTimes and Washington Post. Salk professor
Ronald Evans posed a series of questions to
Pollan, who responded by covering topics
ranging from how he got his start writing
about food, agriculture and the environment,
to his thoughts about America’s obesity
epidemic and the food movement. The
discussion was followed by a Q&A session
with the audience and a reception.
As the grandson of a produce distributor
and wholesaler, Pollan developed an interestin food and gardening at an early age. He
grew his first garden at the age of eight andreturned to gardening in his late twenties.

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Institute News Inside Salk 8 | 14

It was these experiences that sparked his
interest in the relationship between humans
and nature.
“It was my mishaps in that garden thatreally launched me,” he says. “I thought,
this is my subject; I’m going to write about
nature in these messy places where humans
and the natural world have to engage with
one another.”Over the past 25 years, Pollan has
written books and articles about the perilsof the industrial food chain. In The
Omnivore’s Dilemma he traces four foodchains—industrial, big organic, local farmand hunter-gatherer—and examines howwhat we eat affects our health and theenvironment. Pollan says that writing
The Omnivore’s Dilemma changed his
eating habits.
“I eat very differently,” he says. “What
I’ve learned about nutrition and health haschanged my behavior.” In particular, he has
focused on fresh and local foods.

Pollan has long warned of the dangers
behind industrial farming and has becomea leading advocate for reforming the nation’s
agricultural policies. He traces the start ofAmerica’s obesity epidemic to agriculture
subsidy policies enacted in the 1970s. The
subsidies favored some foods over others,with corn and soybeans taking the lead.
“Certain kinds of calories got reallycheap,” he says, noting the importance ofpolicies in shaping food trends.
At the conclusion of his talk, Pollan
was asked what he believes is the secret tolongevity. His advice was simple: everythingin moderation and a focus on fresh foods.
“Nutrients are still very confusing,” he says,
adding that maybe someday scientists candesign food intakes to maximize health but“in the meantime, we should focus on eating
real food.”

www.salk.edu

Second annual Step into Discovery brings the community to the Salk
ON SATURDAY, APRIL 12, THE SALK INSTITUTE INVITED THE SAN
Diego community onto campus and more than 1,100 people came out fora day of fun and learning at the second annual Step into Discovery.
More than 600 walkers participated in the 5K Walk for Salk, arriving as
early as 8 a.m. to pick up T-shirts and goodie bags and enjoy a gluten-freebreakfast from Escondido-based GNI Bakery. After the walk, visitors had achance to browse sponsor booths and a steady stream of budding scientists
filtered through the Kids’ Discovery Zone to learn about the brain, plants,
disease modeling and cancer.

www.salk.edu

Visitors were also treated to talks by Jonas Salk’s son, Dr. Peter Salk,
and two of the Institute’s faculty members, Sreekanth Chalasani andJanelle Ayres. More than 500 people participated in Explore Salk tours,
getting a peek inside the Institute’s laboratories and technology corefacilities. In all, 15 labs and three cores opened their doors to the tours.
Many volunteers and staff helped make Step into Discovery 2014
an enjoyable and educational event for the community, while sponsors,
including title sponsor Rudolph and Sletten, ensured that the day was atremendous success.

Inside Salk 8 | 14 Institute News

21

Backward glances at

Back to Basics
lectureTHE THEME WAS SALK HISTORY ON
March 25, when Suzanne Bourgeois,
professor emerita and founding director of
the Regulatory Biology Laboratory, addressed
an audience of more than 100 about theearly years of the Institute. The author of
Genesis of the Salk Institute: The Epic of
Its Founders, Bourgeois was the featured
attraction at the spring Back to Basics
lecture, held in the Institute’s Conrad T.
Prebys Auditorium. She discussed the book,which was published last summer by the
University of California Press, and sharedarchival photographs and inside stories about
the founding of the Salk. Her talk sparked an

animated Q&A session that continued into
the reception and book signing following thelecture, and all copies of the book on handsold out.
Back to Basics is a free biannual lecture
series that is open to anyone interested inlearning more about Salk science. The next

installment will be held Tuesday, September
23, and will feature Ronald Evans fromthe Gene Expression Laboratory, who willtalk about his latest research. For more
information, contact Jennifer Rothrock,at 858-453-4100 ext. 2068, or
jrothrock@salk.edu.

Salk microflora researcher Janelle Ayres named
Searle Scholar
JANELLE AYRES, ASSISTANT PROFESSOR IN THE NOMIS FOUNDATION LABORATORIES
for Immunobiology and Microbial Pathogenesis, has received the prestigious Searle Scholaraward, which each year is given to only 15 researchers in the chemical and biological sciences.
The scholarship provides each recipient with $300,000 to support scientific research over the
next three years. This year, 172 applications were considered from recently appointed assistantprofessors, nominated by 120 universities and research institutions.
Ayres’ work focuses on the trillions of bacteria that live in intestines and are responsible forhealth and wellness. Many diseases occur when that microbial system is thrown out of whackand “bad” bacteria take over. Using antibiotics to fight infections has limitations: besides notworking for all diseases, antibiotics also kill good bacteria and contribute to multi-drug-resistantharmful bacteria (“super bugs”). Ayres focuses on an entirely new approach to therapeutics byinvestigating how helpful microflora could be leveraged to combat the effects of harmful bacteria
in place of or in addition to antibiotic treatment. Rather than attempting to eliminate the badbacteria directly, she is using beneficial bacteria to target and control the damage generated
during infections (for example, diarrhea and rapid weight loss), thereby giving an organism’s
immune system time to clear out the infection. Studying how to engineer microbes that cancolonize the intestine while providing beneficial effects could lead to new treatments for infectious
and inflammatory diseases and pathologies associated with cancer and aging.

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Institute News Inside Salk 8 | 14

www.salk.edu

Ronald Evans, director of the Gene Expression Laboratory, holder of the March of Dimes Chair in Molecular and Developmental Biology
and a Howard Hughes Medical Institute investigator, received an honorary doctorate for outstanding scientific research from the Universityof Groningen, one of the oldest and largest universities in the Netherlands. The university created a mini-documentary featuring Evans as
one of “10 Extraordinary Scientists.”

San Diego developer Donald Cohn elected to
Salk Board of Trustees
IN APRIL, LONGTIME SAN DIEGO REAL
estate developer and community builder Donald
Cohn became the newest member of the Salk
Institute Board of Trustees.
“Donald’s success as a businessman,philanthropist and community volunteer makehim a vital asset to our board,” says chairman
Irwin Jacobs. “We are greatly pleased to have
him join our Board of Trustees.”
Cohn established his business career in San
Diego in 1961. From then through 1979, he
was active in the development of over 3,000
residential units, both as a builder and investor.
In 1980, he founded DataQuick Information
Systems, serving as CEO and managing its
growth as it became the largest real estate
information provider in the United States;
it was sold to Acxiom Corporation in 1995.

www.salk.edu

Subsequently, he was founder and CEO of DTS
Communications until its sale to a New York
Stock Exchange firm in 1997. Since that time,
he has been an investor in other businessventures and continues to manage his realestate portfolio.
Cohn is a past chair of the Old Globe
Theatre and director of the Plaza de Panama
Committee (Balboa Park project). In 2006, heand his wife, Karen, gave $5 million to the Old
Globe to establish the Karen and Donald Cohn
Education Center, the theater’s first dedicatedspace for education and outreach programs.
The Cohns have also supported the
San Diego Opera; San Diego Symphony;
The Bishop’s School; University of California,
San Diego; University of San Diego; and theMuseum of Contemporary Art San Diego.

Inside Salk 8 | 14 Institute News

23

Left upper: Fei-Fei Dong, Right upper: Clodagh O’Shea

Lower left: Marc Montminy, Lower right: Karen Joy Davis and Sean Lee

Spectacular first season of Salk

Science & Music Series
concludes; lineup announced for next year
ON MAY 18, THE INAUGURAL SALK SCIENCE & MUSIC SERIES
concluded with a remarkable performance by pianist Fei-Fei Dong anda fascinating scientific talk by Salk associate professor Clodagh O’Shea.
The six-part series, which began in October, brought together virtuosos
from the worlds of both music and science. Because of its resounding
success, the series will return for a second season beginning in the fall.
The seed for the Salk Science & Music Series was planted when
Salk president William Brody envisioned a continuation of the Salk
tradition of combining science and art in imaginative ways. Observing
the many parallels between art and science, he knew that attracting
music lovers to the Salk would naturally tie in with the creative
approaches scientists employ in their research. Each concert features
performances by some of the hottest established and emerging
classical and jazz musicians, along with talks about the latest discoveries
by the Institute’s world-renowned scientists.
“The combination of science and music is in keeping with Jonas
Salk’s original vision for the Institute, which is to merge science andart,” he explains.
Longtime Salk supporter and former trustee Conrad Prebys generously
donated a magnificent Steinway concert grand piano, which anchors theseries. Concert pianist Karen Joy Davis served as executive producer.

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“The gift of the Steinway concert grand inspired the creation of theseries,” Davis says. “A great piano needs to be played and enjoyed!
I think the Salk’s amazing history of discovery and its iconic architecture
make it the perfect setting for combining music and science.”
Using her extensive contacts in the classical music world, Davis wasable to attract the world-class talent that marked the first season. Once theprogram came to life, it was quickly embraced by the San Diego community.
A stellar lineup has already been slated for the upcoming second
season of the Science & Music Series, which will open in November
with jazz piano phenom Eldar Djangirov and his trio and conclude with
the Brubeck Brothers Quartet in June. Other performances will include
pianist Sean Chen, 2013 Van Cliburn Crystal Award winner; Karen Joy
Davis and Rachel Kudo in a duo piano concert; Ching-Yun Hu, winner ofthe 2008 Arthur Rubinstein International Piano competition; and pianist
Giuseppe Mentuccia.
For a complete schedule of the second Salk Science & Music Series andinformation about tickets, please visit http://music.salk.edu/. President’s
Club members receive admission and premier seating to all Salk Science &Music Series concerts, as well as an invitation to a post-concert reception.
For information about joining the President’s Club, visit http://www.salk.edu/
support/presidentsclub.html or call (858) 453-4100, ext.1405.
www.salk.edu

Be amazed and inspired

PLEASE JOIN US AS WE CONTINUE THIS EXCITING JOURNEY INTO OUR SECOND SEASON

Sunday, December 7, 2014

Sunday, November 2, 2014
ELDAR TRIORACHEL KUDO & KAREN JOY DAVISJazz pianist virtuoso, Eldar Djangirov, returns
to San Diego to perform with his Trio

Duo piano concert, featuring Tchaikovsky’s
Nutcracker Suite“Kudo is an extraordinary artist who“His command of the instrument”

is beyond staggering.

—Bob Doershuk: Downbeat Magazine”

promises to become a legend.

—El Nuevo Herald“Ms. Davis' performance was unique andassured...displayed sparkling brillianceand technical accuracy. —The London TimesTERRY SEJNOWSKI

Professor and Director,
Vision Center Laboratory

Professor and Laboratory Head
Computational Neurobiology Laboratory

Sunday, January 25, 2015

Sunday, February 22, 2015

GIUSEPPE MENTUCCIASEAN CHEN“This young pianist has warmth,“Sean Chen has the rare ability to combine

Pianist, 2013 Van Cliburn Crystal
Award winner

Winner of the 2006 Vittoria Prize from the
Accademia Nazionale di Santa Cecilia”

musical intelligence and an innate electricity.

—Talk in New YorkTONY HUNTER

Professor, Molecular and Cell Biology Laboratory

Sunday, April 26, 2015
CHING-YUN HU

Winner, 2008 Arthur Rubinstein International
Piano competition

poetic musical sensibilities and dazzlingtechnical prowess. —Paula Edelstein, LA Music Examiner”

INDER VERMA

Professor, Laboratory of Genetics

Sunday, june 7, 2015
BRUBECK BROTHERS QUARTET
Tribute to Dave Brubeck concert“Ching-Yun Hu possesses the soul of Chopin.”“Once again the Brubeck Brothers Quartet

JUAN CARLOS IZPISUA BELMONTESATCHIN PANDA—Chopin International Festival, Duszniki-Dzroj, Poland

Professor, Gene Expression Laboratorywww.salk.edu”

TOM ALBRIGHT

attains that rarefied level where music is
both relaxed and expressive. —All About Jazz”

Associate Professor,
Regulatory Biology Laboratory

Inside Salk 8 | 14 Institute News

25

Scientific symposia markmilestone birthdays for Ronald Evans and Geoffrey Wahl

T

WO OF THE INSTITUTE’S MOST
distinguished senior scientists recently
celebrated landmark birthdays, Salk
style. Daylong scientific symposia for
Geoffrey Wahl’s and Ronald Evans’ 65th birthdays
paid homage to their remarkable careers,
featuring tributes by colleagues and presentations
by speakers who had played important roles in theirprofessional lives. Family members and friends also
put in guest appearances, and the proceedings
were leavened with liberal doses of good-natured
ribbing. Each symposium ended with remarks by
the honoree, followed by a reception.
The festivities began April 4 with the symposiummarking Wahl’s 65th birthday, although it was nearlya year late, rescheduled to coincide with the 2014
annual meeting of the American Association forCancer Research (AACR), which was held in San

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Institute News Inside Salk 8 | 14

Diego. (Wahl served as president of the organizationin 2006.) Guest speakers included 2007 Nobel
laureate Mario Capecchi of the University of Utah,
who had been Wahl’s doctoral advisor; George Stark,from the Cleveland Clinic’s Lerner ResearchInstitute, his postdoctoral mentor; Peter Jones,
from USC’s Norris Comprehensive Cancer Center,also a former president of the AACR; Arnie Levinefrom the Institute for Advanced Study; Gigi Lozano
from the M.D. Anderson Cancer Center; and Dan
Von Hoff from TGen (the Translational Genetics
Institute) in Phoenix, Arizona. As a sabbatical visitor
in Wahl’s lab, Von Hoff got him interested in bothtranslational research and the AACR.
Evans’ 65th birthday symposium, held June 2,
featured his postdoctoral advisor, James Darnell ofRockefeller University; Leslie Anne Leinwand from the
University of Colorado; Bert O’Malley, a colleague fromwww.salk.edu

Colleagues and friends join Ronald Evans in celebrating his 65th birthday.

Baylor College of Medicine; Pierre Chambonof IGBMC in France, a “friendly competitor”
who shared the 2004 Lasker Prize with Evans;former postdocs David Mangelsdorf of the
University of Texas Southwestern Medical
Center; Katja Lamia from The Scripps ResearchInstitute; and 1985 Nobel laureate Joseph
Goldstein of the University of Texas Southwestern Medical Center.
Following the formal part of each program,the honoree was presented with a walker
and other gag gifts. Salk’s senior illustrator
Jamie Simon created humorous posters for the
symposia–Wahl’s, a take-off of Dr. Strangelove,and Evans’, a play on A Beautiful Mind—
establishing a tone that was equal parts
serious science and lighthearted homage to
two world-class investigators.

www.salk.edu

Whimsical posters announcing the birthday symposia for Ronald Evans (left) and Geoffrey Wahl (right).

Inside Salk 8 | 14 Institute News

27

Janelle Ayres

Salk Women & Science continues to gain momentum
MORE THAN 100 FEMALE BUSINESS AND
community leaders gathered at Salk on March
5 for a Women & Science event featuring atalk by Janelle Ayres, of the Nomis Center for
Immunobiology and Microbial Pathogenesis.
Ayres’ talk, “Good bugs vs. bad bugs: Using
the intestinal microbiota to treat infectious
diseases,” was an overview of her research
into the defense strategies that enable a hostto survive when interacting with microbes,
and she explained how understanding thesemechanisms can lead to new treatments for
infectious and inflammatory disease.
Salk chief operating officer and executive
vice president Marsha Chandler welcomed
guests to the event, and Greg Lemke, aprofessor in the Molecular Neurobiology
Laboratory and holder of the Françoise
Gilot-Salk Chair, introduced Ayres’ talk.
Salk Women & Science was launched inJuly 2012 to engage the community in biological science and technology and ultimately

support the advancement of women inscience. Three Women & Science events
are offered annually, as well as small private
dinners hosted by female faculty. The next
event will take place in October. For more
information about Women & Science, visit
www.salk.edu/womenandscience.

From left to right: Marsha Chandler, Greg Lemke, Julie Law

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www.salk.edu

From left to right: Meredith Counce, Sam Pfaff, Clodagh O’Shea, William Brody, Charlotte Jones Anderson, Ronald Evans, Rebecca Newman, Inder Verma

FOUNDATION LEADERS BRUSH UP ON TAX LAWS AND FOUNDATIONMANAGEMENT AT THE
ND

42 ANNUAL

FOR PRIVATE FOUNDATIONS

14-162014

MAY

A SERIES OF NATIONALLY KNOWN LECTURERS AND AUTHORS“The seminar continues to be an extremely useful forum forprovided insights on foundation law, management, finance andtrustees to learn about the latest developments in tax law andgovernance on May 14-16 at the Salk Institute’s 42nd annual

to interact with tax experts and foundation peers,” says

Tax Seminar for Private Foundations. Sixty foundation leaders

Rebecca Newman, Salk’s vice president of external relations.

from across the country were in attendance at the event, which

Whether covering the complexities of changes in tax law oroffering new ideas and perspectives, the seminar provides awas held at the Lodge at Torrey Pines.
“Beyond the excellent presentations and La Jolla’s summer-likewealth of resources for foundation leaders.

weather, the conference offered several special events,” notes tax
seminar chairman Edwin Hunter, president of Hunter, Hunter &From left to right: Elaine Marshall, Susie Spanos, Pierce Marshall, Charlotte Jones Anderson

Sonnier, LLC.
Many community members joined seminar participants forthe keynote address by Charlotte Jones Anderson, executive vice

SALK
INSTITUTE

president of the Dallas Cowboys and chair of NFL Charities. Her
presentation, titled “How passion and compassion have shaped

the Dallas Cowboys,” focused on the synergy between the private
philanthropy of the Jones family and the Dallas Cowboys brand,
offering a fascinating perspective on philanthropy as a dynamic

FOR BIOLOGICAL STUDIES

part of a family business.
Attendees also heard scientific updates from Salk scientists
Inder Verma, Janelle Ayres and Terrence Sejnowski. Dr. Peter Salk,
son of Institute founder Jonas Salk, spoke about his father’s legacy
and the global impact of his work.

www.salk.edu

Inside Salk 8 | 14 Institute News

29

Geoffrey Wahl elected to Academyof Arts and Sciences Class of 2014
for outstanding scientific work
LAST APRIL, THE AMERICAN ACADEMY OF ARTS AND SCIENCES(AAAS) elected Geoffrey Wahl, a professor in Salk’s Gene Expression
Laboratory and holder of the Daniel and Martina Lewis Chair, to its
distinguished membership. The society’s ranks include Nobel laureates,
Pulitzer Prize recipients and Oscar winners, as well as intellectual
luminaries dating back to the founding of the United States. George
Washington and Benjamin Franklin were members, as was Albert Einstein.
Wahl joins 13 other Salk professors as members of the organization.
Wahl seeks to determine how cancers originate and progress and whytumors become resistant to even the most powerful anti-cancer drugs.
His goal is to translate the knowledge gained from basic research into
the development of new treatment strategies to manage all types ofcancer more effectively.
“It has been my privilege to call Geoff a colleague and a dear friend,”
says Inder Verma, a professor in Salk’s Laboratory of Genetics andAmerican Cancer Society Professor of Molecular Biology. “His work inunderstanding cancer has been critical to the field, and he is highly
deserving of this honor.” Verma, along with Carol Prives, a professor atColumbia University, nominated Wahl for membership in the academy;both are AAAS members themselves.
“I am humbled by the honor and privilege of being included as amember of this academy and deeply grateful to those who nominatedand supported me,” says Wahl. “I have been fortunate to work withstudents, postdoctoral scholars and collaborators whose efforts, insights
and intellect were vital to my work.”

The academy is one of the country’s oldest and most prestigious
honorary learned societies and a leading center for independent policy
research. The current membership includes more than 250 Nobel laureatesand more than 60 Pulitzer Prize winners. Other members elected in 2014
include authors John Irving and E. Annie Proulx, cartoonist Jules Feiffer,actor Al Pacino, political economist Robert Reich, former Paramount CEO
Sherry Lansing and oceanographer Robert Ballard, along with a host ofillustrious scientists, mathematicians, engineers, economists, historians,social scientists, educators, philanthropists, artists and more.

Salk Board of Trustees tours the Waitt Advanced Biophotonic Centerwith assistant professor Axel Nimmerjahn and staff on April 10.

Salk Trustees Ernest and Evelyn Rady, Linda Chester, Ben Lewis, Alan Gold and Fred Dotzler visit the laboratory of Salk professor Axel Nimmerjahn.

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www.salk.edu

Inder Verma

Ronald Evans

Two faculty inducted into the 2014 elected class of fellows of
the American Association for Cancer Research Academy
THE AMERICAN ASSOCIATION FOR CANCER

a peer-review process that evaluates individuals

Evans, director of the Gene Expression

Research (AACR), the world’s oldest and largest

on the basis of their innovative and influential

Laboratory, is the March of Dimes Chair in

professional society dedicated to advancing

scientific achievements in cancer research.

Developmental and Molecular Biology andcancer research, inducted Salk professors

Verma, who is holder of the Irwin and Joana Howard Hughes Medical Institute investigator.

Ronald Evans and Inder Verma into its 2014

Jacobs Chair in Exemplary Life Science andEvans is a leading authority on hormone signals,

class of elected fellows in April.

American Cancer Society Professor of Molecularmany of which he discovered are primary targets

Biology, is renowned for developing innovativein the treatment of leukemia and pancreatic,

who have made exceptional contributions togene therapy techniques that have led to abreast and prostate cancers.

cancer research or cancer-related biomedical

better understanding of tumors, cancer stem

science and whose work has had a major impact

cells and cancer-related genes.

The AACR Academy recognizes scientists

in their fields. The fellows are elected throughCancer metabolism expert Reuben Shaw
promoted to full professor
REUBEN SHAW, A MEMBER OF THE MOLECULAR

tells cells to lower their glucose, lipids and growth.

and Cell Biology Laboratory and a Howard Hughes

The pathway halts the growth of tumor cells, which

Medical Institute early career scientist, has been

have an aberrant revved-up metabolism, but also

promoted from associate professor to full professor

restores normal function to the liver and otherafter a rigorous evaluation process by Salk senior

tissues in diabetics. Shaw’s lab recently followed

faculty, non-resident fellows and scientific peers.

up on a prediction from its previous studies to test

“We are pleased to recognize Professor Shaw’s

whether drugs widely used to treat type 2 diabetes

original, innovative and notable contributions to

could work as cancer treatments. The team foundbiological research in pathways that underlie thespecific efficacy in some forms of lung cancer for

development of cancer and metabolic disorders,”

which there are currently no good therapies.

says Salk president William Brody.
While investigating one of the most commonly

Researchers in Shaw’s lab also use genetic
mouse models to further examine the connections

mutated genes in lung cancer, Shaw discovered an

between cancer and metabolic diseases and toenergy-sensing pathway that shuts down cell growthtease out the precise role of each component ofand reprograms metabolism when nutrients are

the signaling pathway. In the past five years

scarce. His lab went on to molecularly decode a

at Salk, the lab’s studies have led to thenumber of new components of this biochemical

discovery of new therapies for both cancer

pathway, which connects nutrition and exercise to

and type 2 diabetes.

suppression in both cancer and diabetes.
This biochemical circuit, the AMPK pathway,
is activated by exercise and caloric restriction andwww.salk.edu

Inside Salk 8 | 14 Institute News

31

Salk’s Dona Mapston leads students in science-focused activities as part of the Institute’s Education Outreach program.

Education Outreachlaunches innovative programs to promote science education
IF PAST HISTORY IS ANY INDICATION, SALK’S
award-winning Education Outreach program may
be poised to garner a few new accolades in the
not-too-distant future. Not only has it introduceda brand-new program that promotes virtual interactions between Salk scientists and elementary
school students, but it recently received one ofjust seven pilot grants awarded by the American
Academy of Arts and Sciences (AAAS) throughthe organization’s new STEM (Science, Technology, Engineering and Mathematics) Volunteer
Program. Add these groundbreaking initiatives
to Education Outreach’s existing High School
Scholars program, March of Dimes High School
Science Day and Mobile Science Lab, and it’san even stronger formula for success in attracting young people to science studies and careers.
SciChat, the program for elementary students, uses Skype to enable students at Del Mar

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Institute News Inside Salk 8 | 14

Hills Academy of Arts and Sciences in Del
Mar, California, to ask Salk scientists generalquestions about their research and what it’s liketo work in the field. The project’s goal is to let
the students interact with scientists so they can
picture themselves in similar roles someday.
“We are thrilled to have this new opportunity
for young students to meet and talk with ourscientists,” says Ellen Potter, director of the
Education Outreach program. “We are now
able to bring the Salk to the students when thestudents can’t come to us. It is a great way toextend our outreach and share our excitement
for scientific discovery.”
The first SciChat took place February 11,
when Abby Buchwalter, a postdoctoral fellow in
Martin Hetzer’s lab, described her research tonearly 30 fourth-, fifth- and sixth-grade students
during their lunch break. Seven more SciChats

took place over the next four months, andplans call for the popular program to continue
into the next academic year.
The AAAS grant will fund a pilot initiative
at Salk called New Frontiers in Science
Education. The program will bring San Diegoarea high school science teachers together
with Salk scientists to develop curricula basedon the state-of-the-art research taking placeat the Institute. Ronald Evans, an HHMI
investigator, holder of the March of Dimes
Chair in Molecular and Developmental Biology
and an international authority on hormones
who has long been committed to fostering
relationships with local educators, sponsoredthe proposal on behalf of Salk.
During the first year of the project, threeteachers and Salk scientists, including Evans,
will take part in focus groups and workshops

www.salk.edu

“We are now able to bring Salk to the students when students can’t cometo us. It is a great way to extend our outreach and share our excitement
for scientific discovery.

”– ELLEN POTTER

Students gather in the Salk courtyard with Salk scientists and staff during
March of Dimes High School Science Day.

to identify specific areas of Salk research that
lend themselves to adaptation for the classroom.
Working collaboratively, the scientists and teachers will then develop appropriate curriculum andsupport materials that incorporate elements ofstate and national science standards. Local highschool teachers will be recruited to participate
in the second year of the grant, and during thesummer, the teachers will also have opportunities to spend time in the laboratory with avolunteer research scientist to observe how
actual research is carried out.
“This is an extraordinary opportunity toleverage the scientific expertise of Salk
investigators and the enthusiasm and classroom
experience of the participating teachers,” says
Dona Mapston, Education Outreach specialist.
“It will be fascinating to see what comes out ofthe process.”www.salk.edu

March of Dimes High School
Science Day ignites interestin future scientists
MORE THAN 230 HIGH SCHOOL STUDENTS FROM 23 CAMPUSES
throughout San Diego County converged on the Salk March 1 for the2014 March of Dimes High School Science Day. The half-day science
immersion program exposed participants to a variety of experiences, withthe aim of sparking their interest in the field. In the morning, following welcoming remarks by Salk president William Brody, Salk employee
volunteers shepherded groups of students to labs across the campus
where they took part in hands-on science experiments under the directionof postdocs and graduate students. Following lunch, attendees enjoyeda talk by Sreekanth Chalasani, an assistant professor in the Molecular
Neurobiology Laboratory, who spoke about c. elegans as a model organism.
All students left with a logoed string backpack and new perspectives onscience and the possibilities of science careers.

Inside Salk 8 | 14 Institute News

33

Jared Diamond visits the Salk
PULITZER PRIZE-WINNING AUTHOR AND UNIVERSITY OF CALIFORNIA,
Los Angeles professor Jared Diamond, whose bestselling works include Guns,
Germs, and Steel as well as Collapse, spoke to a packed auditorium on socialand science crises for Salk’s Francis Crick Lecture in April.

Salk scientist

Vicki Lundblad
wins accolades

VICKI LUNDBLAD, A PROFESSOR IN
the Molecular and Cell Biology Laboratory,
has been awarded the Becky and Ralph
S. O’Connor Chair in recognition of her
excellence in the field of molecular and cellbiology. Ralph O’Connor, who serves on the
Salk Board of Trustees, and his wife, Becky,
generously created the chair as an “investment that has the potential for maximum
impact on human health.”
Lundblad has also been elected a2014 Fellow of the American Academy ofMicrobiology for her pioneering work intelomere biology. Fellows are elected annually
through a highly selective process based on
significant contributions to the field of
microbiology, a field that boasts the names

34

Discovery Roundup Inside Salk 8 | 14

of Louis Pasteur, Jonas Salk and manyothers responsible for some of the greatest
achievements in biomedical history.
Lundblad’s research has defined a key
molecular mechanism that is critical in both
aging and cancer. She found that the ends
of chromosomes, known as telomeres,shorten over time, acting as a “molecular
clock” that counts down the number of times
a cell can divide. She has also shown that atelomere-dedicated enzyme called telomerase can help reset the clock and increase
cell division. Figuring out how to control
this molecular clock suggests the tantalizing
possibility of both halting cancerous cells
and promoting healthy aging. Toward that
end, Lundblad’s lab is currently teasing out
the pathways that either promote or inhibit
telomerase inside cells.

www.salk.edu

Discovery Roundup

Fred Gage and Kristen Brennand

New stem cell research points to early indicators of schizophrenia
CURRENTLY, OVER 1.1 PERCENT OF THE
world’s population has schizophrenia, with anestimated 3 million cases in the United Statesalone. The economic cost is high: in 2002,
Americans spent nearly $63 billion on treating
and managing the disability. The emotional
cost is higher still: 10 percent of those withschizophrenia are driven to commit suicide.
Yet, scientists still know little about its
underlying causes and do not know which cells
in the brain are affected and how. Previously,
it had only been possible to study schizophrenia
by examining the brains of patients after death,but age, stress, medication or drug abuse had
often altered or damaged the brains, making
it difficult to pinpoint the disease’s origins.
Using new stem cell technology, scientists
in the lab of Fred Gage have shown thatneurons generated from the skin cells of people
with schizophrenia behave strangely in early
developmental stages. The findings of thestudy, published in Molecular Psychiatry, areconsistent with a prevailing theory thatevents during pregnancy can contribute toschizophrenia, even though the disease doesn’t
manifest until early adulthood.
“This study aims to investigate the earliest
detectable changes in the brain that leadto schizophrenia,” says Gage, who heads Salk’s
Engman Laboratory for Schizophrenia Research.
“We were surprised at how early in the developmental process defects in neural function could
be detected.”
Taking skin cells from patients, Gage’s
team coaxed the cells to revert back to an
earlier stem cell form and then prompted themto grow into very early stage neurons (dubbed
neural progenitor cells or NPCs), which aresimilar to the cells in the brain of a developing fetus. They generated NPCs from the skincells of four patients with schizophrenia andsix people without the disease, then tested thecells in two types of assays. On both tests, theresearchers found that NPCs from people withschizophrenia differed in significant ways fromthose taken from unaffected people.
Kristen Brennand, the paper’s first author
and now an assistant professor at the Icahn
School of Medicine at Mount Sinai, said theresearchers were surprised that the skin-derived
neurons remained in such an early stage ofdevelopment. “We realized they weren’t matureneurons but only as old as neurons in the firsttrimester,” she says. “So we weren’t studying
schizophrenia but the things that go wrong along time before patients actually get sick.”
According to Gage, the study hints that there
may be opportunities to create diagnostic tests
for schizophrenia at an early stage. The research
was supported in part by the Robert and Mary
Jane Engman Foundation.

These images show the movement of patient-derived neuralprogenitor cells from a sphere of neurons in a migration assay.
How far and how quickly the neurons move indicates whether
they may behave atypically in the brain.

www.salk.edu

Inside Salk 8 | 14 Discovery Roundup35

“We really never expected that
we would be able to decouple
the sleep-wake cycle and theeating cycle, especially with asimple mutation.

”– SATCHIDANANDA PANDA

Genes discovered linking circadian clockwith eating schedule
FOR MOST PEOPLE, THE URGE TO EAT A MEAL OR SNACK COMES
at a few predictable times during the waking part of the day. But for thosewith a rare syndrome, hunger comes at unwanted hours, interrupts sleepand causes overeating. A team in the lab of Satchidananda Panda
recently discovered a pair of genes that normally keeps eating schedules
in sync with daily sleep rhythms. In mice with mutations in one of thegenes, eating patterns are shifted, leading to unusual mealtimes andweight gain. The results were published in Cell Reports.
“We really never expected that we would be able to decouple thesleep-wake cycle and the eating cycle, especially with a simple mutation,”says Panda, whose work is supported in part by the Joe W. and Dorothy
Dorsett Brown Foundation. “It opens up a whole lot of future questions
about how these cycles are regulated.”
More than a decade ago, researchers discovered that individuals withan inherited sleep disorder often carry a particular mutation in a protein
called PER2, in an area of the protein that can be phosphorylated—theability to bond with a phosphate chemical that changes the protein’s function. Humans have three PER, or period, genes, all thought to play a rolein the circadian clock and all containing the same phosphorylation spot.
Panda’s lab joined forces with a Chinese team led by Ying Xu of Nanjing
University to test whether mutations in the equivalent area of PER1 would
have the same effect as those in PER2. They bred mice to lack the mouse36

Discovery Roundup Inside Salk 8 | 14

period genes and added in a human PER1 or PER2 with a mutation in
the phosphorylation site. As expected, mice with a mutated PER2 had
sleep defects, dozing off earlier than usual. The same wasn’t true for
PER1 mutations, though.
Mice with the PER1 phosphorylation defects ate earlier than othermice. The defect caused them to awaken and snack before their sleep
cycle was over, and eat more food throughout their normal waking period.
When researchers looked at the molecular details of the PER1 protein,
they found that the mutated PER1 led to lower protein levels during thesleeping period, higher levels during the waking period and a faster
degradation of protein whenever it was produced by cells. Panda andhis colleagues hypothesize that normally, PER1 and PER2 are kept
synchronized, but a mutation in one of the genes could break this link
and cause off-cycle eating or sleeping.
When the team restricted access to food, providing it only at themice’s normal meal times, they found that even with a genetic mutationin PER1, mice could maintain a normal weight. Over a ten-week follow-up,
these mice—with a PER1 mutation but timed access to food—showed
no differences compared to control animals. This tells the researchersthat the weight gain caused by PER1 is entirely caused by meal mistiming,
not other metabolic defects.

www.salk.edu

Discovery Roundup

V2b interneurons, responsible for a key locomotion circuit, appear as
green with yellow nuclei in a spinal cord while all other neurons are red.

Discovery reveals circuitry offundamental motor circuit
THE SPINAL CORD CONTAINS A NETWORK OF NEURONS THAT ARE
able to operate largely in an autonomous manner, thus allowing animals
to carry out simple rhythmic walking movements with minimal attention—
giving us the ability, for example, to walk while talking on the phone.
These circuits control properties such as stepping with each foot or
pacing the tempo of walking or running.
Recently, a team of researchers led by Martyn Goulding identified
for the first time which neurons in the spinal cord are responsible forcontrolling a key output of this locomotion circuit, namely, the ability
to synchronously activate and deactivate opposing muscles to createa smooth bending motion (dubbed flexor-extensor alternation). The
findings were published in Neuron.
Motor circuits in the spinal cord are assembled from six major typesof interneurons—cells that interface between nerves descending fromthe brain and nerves that activate or inhibit muscles.
Goulding and his group had previously implicated one class ofinterneurons, V1, as being a likely key component of the flexor-extensor
circuitry. When V1 interneurons were removed, however, the team saw
www.salk.edu

that flexor-extensor activity was still intact, leading them to suspect that
another type of cell was also involved.
To determine what other interneurons were at play in the flexor-extensor
circuit, the team looked for other cells in the spinal cord with properties
similar to those of the V1 interneurons and began to focus on anotherclass of neuron whose function was not known—V2b interneurons. Usinga specialized experimental setup that allows one to monitor locomotionin the spinal cord itself, the team saw a synchronous pattern of flexor andextensor activity when V2b interneurons were inactivated along with theV1 interneurons.
“Our whole motor system is built around flexor-extension; this is thecornerstone component of movement,” says Goulding, who holds Salk’s
Frederick W. and Joanna J. Mitchell Chair. “If you really want to understand how animals move, you need to understand the contribution ofthese switching cells.”
Goulding’s discovery may pave the way for new therapies for spinal
cord injuries or other motor impairments related to disease.

Inside Salk 8 | 14 Discovery Roundup

37

Michal Krawczyk and Beverly Emerson

Salk scientists identify novel regulator of key gene
expression in cancer
THE COX-2 GENE MEDIATES INFLAMMATION,
which in most cases helps our bodies eliminate
pathogens and damaged cells. But inflammation
also has a dark side: it aids growth and spread oftumors in the early stages of cancer. By learning
more about how COX-2 is affected, scientists
may be able to provide a potential target for
future cancer treatment.
Now, a team in the lab of Beverly Emerson
has identified a key genetic switch, a string of
nucleotides dubbed a long non-coding RNA(lncRNA), that acts as an on/off switch for the
COX-2 gene. The function of lncRNAs is notwell understood, but evidence increasingly
points to their role in regulating gene expression,as they are found overexpressed in esophageal,colorectal and breast cancers.
“Deciphering the mechanism of COX-2 gene
regulation is of great clinical interest,” says

38

Discovery Roundup Inside Salk 8 | 14

Emerson, holder of the Edwin K. Hunter Chair.
“COX-2 is instrumental in the development ofseveral types of cancer, including colon, breastand prostate cancer. Strategies that specificallymodulate COX-2 activity could be an attractive
treatment approach.”
Using human mammary epithelial cells,
Emerson and senior scientist Michal Krawczyk
discovered that an lncRNA called PACER kicks
a molecule called p50 off the COX-2 gene,
causing COX-2 to go into overdrive. This is thefirst time scientists have shown that non-coding
RNAs must be activated in order to squelch theactivity of p50, a gene repressor. In turn, says
Krawczyk, blocking p50 promotes the assemblyof molecular activators of gene expression, whichramp up COX-2 activity.
The scientists were also surprised to notean additional potential role for PACER-induced

COX-2 activation in cancer. Early in the disease
process, instead of activating the immune
system to clear malignant cells from the body,
COX-2 aids the growth and spread of tumors.
In later stages of disease, however, Krawczyk
says cancer cells often shut off COX-2 activity,
as if at that stage COX-2 is no longer beneficial
for tumor growth because it exposes spreading
tumor cells to the immune system. That presents
the opportunity to trigger COX-2 expression via
PACER in late-stage cancers to aid immune
system clearance of metastatic cells.
“This could be a potential treatment forlate-stage cancers,” says Krawczyk. “We could
possibly use small molecules to reactivate COX-2
activity, or perhaps even supply PACER itself,
to fight the disease.”
The findings of the study were publishedin eLife.
www.salk.edu

Discovery Roundup

The microscope image on the left shows brain blood vessels (red) with intact junctions (yellow lines) between cells that compose the vessel walls. The image on the right shows blood vessels andjunctions two days after a stroke. Blood material has entered the brain (dark red background). Scientists from the Salk Institute and UC Irvine showed that early blood material leakage (within 6hours after stroke) is due to increased carrier protein transport through the cells of the vessel walls and not through gaps at the junctions, as previously thought.

Researchers identify new cause of brain bleeding
immediately after stroke
STROKE IS NOT ONLY A COMPLEX AND DEVASTATING NEUROLOGICAL
condition; it’s the fourth-leading cause of death and primary reason fordisability in the United States. It results in severe blood-brain barrier damage, which allows entry of blood-borne material into the brain, contributing
to cellular death and permanent cognitive and movement impairments.
Researchers in the lab of Axel Nimmerjahn, collaborating with Dritan
Agalliu, an assistant professor of developmental and cell biology at UC
Irvine, have discovered a new mechanism that allows blood to enter thebrain immediately after stroke, revealing a possible means to create newtherapies that may reduce or prevent stroke-induced damage in the brain.
In their research, Nimmerjahn and Agalliu developed a novel transgenic
mouse strain in which they used a fluorescent tag to see the barrier-formingtight junctions between the cells that make up the blood vessels in the
nervous system. This allowed them to image dynamic changes in thebarrier during and after stroke in living animals.
While seeing that the barrier function was rapidly impaired after stroke(within six hours), they unexpectedly found that this early barrier failure is
not due to the breakdown of tight junctions between the blood vessel cells,
as had previously been suspected, because tight junction breakdown did
not occur until two days after the injury. Instead, they reported dramaticincreases in carrier proteins, called serum albumin, flowing directly into
brain tissue. These proteins travel through the cells that make up the bloodvessels, called endothelial cells, using a specialized transport system that
normally operates only in non-brain vessels or immature vessels within
the central nervous system (CNS). This finding suggests that the transportsystem underlies the initial failure of the barrier, allowing entry of bloodmaterial into the brain within six hours of a stroke.
www.salk.edu

Early regulation of the specialized transport system in the CNS
following stroke may spur development of imaging methods or biomarkers
in human studies to identify the initial stages of stroke and thereby
prevent damage as early as possible.
Plus, says Nimmerjahn, “Our new transgenic mouse strain and imaging
approaches may also allow mechanistic insight into other CNS disorders
associated with blood-brain barrier dysfunction, such as brain infection,
amyotrophic lateral sclerosis or vascular cognitive impairment.” Hislaboratory is currently developing and applying new light microscopic tools
to uncover how CNS immune cells respond to injury, mediate repair andinfluence nervous system function and behavior.
Results of the stroke study appeared in Neuron.

“

Our new transgenic mouse strain andimaging approaches may also allow
mechanistic insight into other CNS
disorders associated with blood-brain
barrier dysfunction, such as brain
infection, amyotrophic lateral sclerosis
or vascular cognitive impairment.
– AXEL NIMMERJAHN”Inside Salk 8 | 14 Discovery Roundup

39

Cian O’Donnell and Terrence Sejnowski

Explaining how memories stick together
OVER THE PAST FEW DECADES, NEUROSCIENTISTS HAVE REVEALEDmuch about how long-term memories are stored. For significant events—for example, being bit by a dog—a number of proteins are quickly made in
activated brain cells to create the new memories. Some of these proteins linger for a few hours at specific places on specific neurons before
breaking down. This series of biochemical events allows us to remember
important details about that event—such as, in the case of the dog bite,
which dog, where it was located and so on.
One problem scientists have had with modeling memory storageis explaining why only selective details and not everything is strongly
remembered. Now Terrence Sejnowski and his group have created a
new model of memory that explains how neurons retain select memories
a few hours after an event. This new framework provides a more
complete picture of how memory works, which can inform research
into conditions such as Parkinson’s, Alzheimer’s, post-traumatic stressdisorder and learning disabilities.
“Previous models of memory were based on fast activity patterns,”
says Sejnowski, a Howard Hughes Medical Institute investigator and holder
of Salk’s Francis Crick Chair. “Our new model of memory makes it possible
to integrate experiences over hours rather than moments.”
By incorporating data from previous literature, Sejnowski and postdoctoral researcher Cian O’Donnell developed a model that bridges findings
from both molecular and systems observations of memory to explain how
this memory window works. Using computational modeling, they showedthat despite the proteins being available to a number of neurons in a given

40

Discovery Roundup Inside Salk 8 | 14

circuit, memories are retained when subsequent events activate the sameneurons as the original event. They found that the spatial positioning ofproteins at both specific neurons and at specific areas around theseneurons predicts which memories are recorded.
The new model, reported in Neuron, also provides a potential framework for understanding how generalizations from memories are processed
during dreams. While much is still unknown about sleep, researchsuggests that important memories from the day are often cycled throughthe brain, shuttled from temporary storage in the hippocampus to more
long-term storage in the cortex. Researchers observed most of thismemory formation in non-dreaming sleep. Little is known about if andhow memory packaging or consolidation is done during dreams. O’Donnell
and Sejnowski’s model, however, suggests that some memory retention
does happen during dreams, and by applying their findings, they came up
with a theoretical model for how the memory abstraction process mightwork during sleep.

“

Our new model of memory makes it
possible to integrate experiences overhours rather than moments.

”– TERRENCE SEJNOWSKI

www.salk.edu

Discovery Roundup

Inder Verma and Amy FirthSalk lab turns skin cells into human airway tissue
STUDYING DISEASES THAT AFFECT THE
lungs and nearby airways has been limitedby the ability to collect diseased tissue frompatients and by the complexity of organs.
Multiple cell types make up airway tissue, so
studying how a disease changes just one cell
type in the lab may not be an accurate reflectionof the full impact of the disease.
Using reprogrammed skin cells, researchers
in the lab of Inder Verma have for the first timeused stem cell techniques to grow fully functional assemblies of the cells that line airways
leading to the lungs. The lab-grown airway tissue
can now be used to study the molecular basisof lung diseases—from rare genetic disorders tocommon afflictions like asthma and emphysema—and to test new drugs to treat the diseases.
The results of the study, a collaboration withFred Gage, were published in Proceedings of
the National Academy of Sciences.

www.salk.edu

In the new work, the researchers developed
the complex airway tissue, composed of four
different cell types, by reprogramming skin cells
into stem cells, then exposing the stem cells toa unique recipe of chemicals that steered themdown a particular airway-specific developmental
path. Since skin cells contain the same masterset of genes as lung cells, any airway tissuegrown from a patient’s skin cells will have thedisease-causing gene mutation in them.
“The ability to generate a variety of cells thatcompose a fully mature lung is the first step tounderstanding the molecular mechanisms ofmany lung diseases,” says Verma, who holds the
Irwin and Joan Jacobs Chair in Exemplary Life
Science and is also an American Cancer Society
Professor of Molecular Biology.
While the grown cells aren’t identical to thosefound in all parts of the lung, similar procedures
could pin down how to grow tissue from othersections of the respiratory system. Already the
new protocol can be used to develop cell populations to study rare diseases, such as primaryciliary dyskinesia, known to affect the cilia lining
airways. In addition, new treatments or genetic
therapies could be tested on lab-grown airway
tissue derived from an affected patient’s cells.
“It will hopefully become possible one
day to correct the genetic mutations in thesetissues and engraft them back into the airwaysof a patient,” says Amy Firth, a postdoctoral
researcher in Verma’s lab and first author of thepaper (see Next Generation, p.16).
Airway tissue grown in the lab could also
reveal how pollutants or nicotine exacerbate
symptoms of diseases not only affected bygenetics but by the air a person breathes.

Inside Salk 8 | 14 Discovery Roundup

41

Glenn Center for
Aging Research receives
additional $3 million fromthe Glenn Foundation for Medical ResearchThis image from the Hetzer laboratory is being used to investigate how theorganization and the architecture of the nucleus influence gene activity.

THE INSTITUTE’S INVESTIGATIONS INTO THE BIOLOGY OF
normal human aging and age-related diseases have received asignificant boost, thanks to a recent $3 million gift from the
Glenn Foundation for Medical Research. The gift will support
Salk’s Glenn Center for Aging Research, which was establishedin January 2009 with a $5 million gift, also from the GlennFoundation. The center draws from 11 of Salk’s leading
laboratories specializing in genetic analysis, stem cell biology
and metabolism research.
“The biology of aging underlies all the major human diseases,”
Glenn Foundation president Mark Collins says. “To understandthe fundamental aging process and to intervene is to delay the42

Philanthropy Inside Salk 8 | 14

onset of disease, to extend the healthful years of life and reduce
costs to society.”
The foundation’s support positions the Glenn Center to rapidly
advance aging research and shed light on ways to stave off amultitude of age-related diseases, such as cancer, cardiovasculardisease, diabetes and Alzheimer’s disease. The center, which
focuses on whole systems biology, organ biology and cellular
aging biology, was the third of eight institutions to join the
Glenn Consortium for Research in Aging, which also includes
Harvard Medical School, MIT’s Department of Biology, Princeton
University and the Stanford University School of Medicine.

www.salk.edu

Salk Institute receives $25 million gift from former
Salk trustee Conrad T. Prebys
IN JUNE, THE SALK INSTITUTE RECEIVED
a milestone gift: $25 million from San Diego
philanthropist and former Salk trustee Conrad
T. Prebys, to support cutting-edge biologicalresearch on a wide range of diseases. The giftis the single largest ever to the Institute’s
endowment, and in honor of Prebys’ generosity,
the Salk Institute auditorium, which regularly
hosts talks by some of the world’s mostprominent scientists, has been named theConrad T. Prebys Auditorium.
“The scientists at Salk are diving deep into
understanding how our bodies operate at themolecular level and what happens when we
get sick,” says Prebys, a prominent real estatedeveloper and stalwart supporter of San Diego
institutions. “It is vital work that must be done
before we can really conquer disease. We
need this foundational science to lay theunderpinnings for new therapies and cures.
I’m honored to play a role in supporting thisimportant research.”
A native of South Bend, Indiana, Prebys wasraised in a neighborhood where most of the residents worked in local factories. Encouraged byan inspirational teacher, he was the first of fivebrothers to graduate from a university. He went
on to found Progress Construction Company, adeveloper of real estate enterprises in California
and Texas.
When he was a child, Prebys’ brother contracted polio, and he saw the power of scientificwww.salk.edu

research to cure disease when Jonas Salk developed the first polio vaccine.
Prebys has long been a supporter of the Salk
Institute and previously served on the Institute’s
Board of Trustees. Earlier, he gave $2 million toestablish the Conrad T. Prebys Endowed Chair
in Vision Research for Thomas Albright, one of
the Institute’s neuroscientists. He has also beena longtime supporter of Symphony at Salk, theInstitute’s annual gala.
His latest gift contributes to the Campaign
for Salk, the Institute’s first-ever fundraising
campaign, and will help grow the Institute’s
unrestricted endowment—one of the prioritiesof the campaign. Funding from unrestricted
endowment allows the Institute to address its
most critical research needs by providing
flexibility in how the funding is used.
The Campaign for Salk was launched publicly
in January 2012, with the goal of raising $300
million by July 2015. Prebys’ gift brings the totalraised so far to more than $275 million.
“Mr. Prebys is renowned for his remarkablegenerosity and his vision in boosting San Diegoby supporting its pillar institutions,” says Salk
president William Brody. “His gift to Salk’s
unrestricted endowment provides the financial
flexibility for Salk to adapt and thrive as technology, science and human needs evolve, leaving alasting legacy.”“

Mr. Prebys is renownedfor his remarkablegenerosity and his visionin boosting San Diegoby supporting its pillar
institutions.

”– WILLIAM BRODY

Inside Salk 8 | 14 Philanthropy

43

Salk Science Leads to Discoveries.

IMPACTING HUMAN HEALTH BEGINS AT THE SALK.

Scientific discovery at the Salk Institute is made possible through annual
contributions from individuals, organizations, corporations and foundations.
Your support will accelerate the pace of breakthroughs in understanding
disease and pave the way to new drug therapies. To learn more, please
visit www.salk.edu/support or call 858.453.4100 x1405.

Get Involved
FRIENDS OF SALK
Unrestricted gifts, in any amount, provide funding where it is most needed and allow our scientists to
conduct critical early-stage research. Contributors up to $2,500 receive Inside Salk magazine and invitations
to annual events.
SALKEXCELLERATORSThe Salkexcellerators program is focused on making Salk science accessible to a younger generation ofbusiness professionals, entrepreneurs and volunteers. Donors receive Inside Salk magazine and invitations
to private receptions and lectures with Salk’s renowned scientists. Salkexcellerators meet in La Jolla and New
York City, and engagement ranges from $500 to $5,000.
PRESIDENT’S CLUBPresident’s Club donors fulfill a central role for the Institute and provide the flexibility to respond to Salk’s
greatest needs. Contributors of $2,500 – $25,000 enjoy unique opportunities to interact with our scientists
in the lab and receive Salk publications.
CHAIRMAN’S CIRCLE
Chairman’s Circle visionary donors support the Institute’s mission with unrestricted annual gifts of $25,000
and above. Their generous support fills a vital need for the Institute by providing the world’s finest minds
in science with the resources to pursue discoveries at the frontier of human knowledge. Donors are invited
to exclusive lab tours and special events with senior researchers that provide opportunities to discuss specific areas of interest. Donors receive Salk publications and individual reports on the impact of their gifts.
SPECIAL PROJECTS
If you have a special interest in one of Salk’s areas of research, such as cancer, aging, diabetes, neuroscience,
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PARTNERS IN RESEARCH
Salk’s legacy society, Partners in Research, welcomes those who have included Salk in their estate plans.
Charitable gift planning is a powerful way of ensuring your legacy lives on, and it can maximize tax and otherfinancial benefits to you, your family, and the Institute. Partners in Research members receive special communications and are invited to events throughout the year.

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Inside Salk 8 | 14

www.salk.edu

William R. Brody, MD, PhD
President, Salk Institute
Irwin Jacobs Presidential ChairBENJAMIN FRANKLIN, PERHAPS THE WISEST OF OUR
nation’s founders, wrote the oft-repeated adage: “An ounceof prevention is worth a pound of cure.” But even the wiseand practical Mr. Franklin made mistakes where prevention
was concerned.
Around the time Franklin wrote these words, a deadly
smallpox epidemic was sweeping across the United States
and the rest of the world. The smallpox inoculation techniqueof the time had originated in Africa. An African servant of theclergyman Cotton Mather in Boston explained to Mather theuse of smallpox inoculation in West Africa. Mather noted thisdown and convinced a local doctor, Zabdiel Boylston, to try
this method during the Boston smallpox outbreak of 1721.
At the time, inoculation used a string that had been drawn
through the pustule of a smallpox victim and then was driedand saved. For inoculation, an incision was made, and thestring was drawn through it to infect the recipient withattenuated smallpox. During that period, the recipient would
be contagious to others but would more often get a milder
form of smallpox with a lower risk of death. The mortality rate
was 2 percent for inoculated people versus 15 percent for
non-inoculated people.
Unfortunately, the Franklin brothers’ Boston newspaper was
critical of the 1721 smallpox inoculation, and Franklin decided
not to inoculate his children, with disastrous consequences.
“In 1736, I lost one of my sons,” Franklin would later write,“a fine boy of four years old, by the smallpox taken in the common
way. I long regretted bitterly and still regret that I had not given
it to him by inoculation.”
Following the Boston outbreak, inoculation became thestate-of-the-art treatment until Dr. Edward Jenner’s discoveryof the more effective and lower-risk cowpox vaccination, which
was published in 1798. (Recipients of Jenner’s vaccine were notcontagious to others, an important improvement.)
Despite being one of the leading thinkers of his time, Franklin
made a tragic miscalculation about the importance of inoculation.
Judging from his famous quip about prevention, he seems towww.salk.edu

have learned from his mistake, yet it is a mistake that continues
to plague individuals and societies—one that finds its roots inpopularized misinformation.
When Jonas Salk introduced his vaccine in 1955, using killed
polio virus particles, the vaccine encountered significant scrutiny
in the press, including an article by the muckraking columnist
Walter Winchell, who claimed the use of the Salk vaccine would
kill thousands of children. It was suspected that inflammatory
journalism was being pushed sotto voce by Salk’s rival, Dr. Albert
Sabin, who was developing an oral vaccine using live attenuatedpolio virus.
The United States switched to the oral polio vaccine (OPV),
but it was eventually abandoned in favor of the Salk vaccine
because there were isolated cases of polio that occurred inchildren who had been inoculated with the OPV.
The philosopher Georg Wilhelm Friedrich Hegel wrote, “Welearn from history that we do not learn from history.” And on theeve of what would have been Jonas Salk’s 100th birthday were
he living today, I have to wonder if Hegel wasn’t right—even as
I hope he wasn’t. Despite the remarkable discovery of the Salk
vaccine, we’ve learned recently that polio has not been eradicatedworldwide. Even more profound, skepticism about the potential
dangers of polio and other vaccines in our country has led toincreasing abandonment of vaccinations, and we are beginningto see the reemergence of diseases like measles and whooping
cough that can be effectively prevented by the use of vaccines.
While the work of Salk scientists doesn’t necessarily leadthem to develop vaccines, many of their discoveries about cells,
bacteria, viruses and immunology lay the foundation for future
vaccine development for diseases like malaria, Ebola and, perhaps
one day, HIV. But these preventives, like those of Franklin’s time
and those available today, will only be effective if they are used.
Franklin’s own poignant experience only serves to emphasizethat the route to wellness and healthy aging is to avoid encountering a disease to the best extent possible, or at least to defer
as long as possible the onset of a debilitating illness.

Inside Salk 8 | 14 Insider’s View

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Salk Calendar
SEPTEMBER
23 Back to Basics Lecture
OCTOBER
7 Salk Women & Science
22 San Diego Salkexcellerators
NOVEMBER
2 Salk Science and Music Series
featuring the Eldar Trio		

DECEMBER
7 Salk Science and Music Series
featuring Rachel Kudo andKaren Joy Davis

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