CH A RT I NG TH E 

FUTURE TOGETHER

The NHLBI 

Strategic Vision

U.S. Department of Health and Human Services

National Institutes of Health

National Heart, Lung, and Blood Institute

CHARTING THE FUTURE TOGETHER

The NHLBI Strategic Vision

National Heart, Lung, and Blood Institute

National Institutes of Health

www.nhlbi.nih.gov
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

ACKNOWLEDGEMENTS

The NHLBI appreciates the extensive input from its staff; the National Heart, Lung, and Blood 

Advisory Council and Board of External Experts, a working group of the Council; and the heart, 

lung, blood, and sleep community in the development of this Strategic Vision.
 THE NHLBI STRATEGIC VISION | 1

Director’s Message . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Strategic Goals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Strategic Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Objective 1: Understand normal biological function and resilience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Compelling Questions & Critical Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Objective 2: Investigate newly discovered pathobiological mechanisms important to the onset and 

progression of HLBS diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Compelling Questions & Critical Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Objective 3: Investigate factors that account for differences in health among populations . . . . . . . . . . . . . . . . . . . . . . . . . 20

Compelling Questions & Critical Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Objective 4: Identify factors that account for individual differences in pathobiology and in responses 

to treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .24

Compelling Questions & Critical Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .25

Objective 5: Develop and optimize novel diagnostic and therapeutic strategies to prevent, treat, and 

cure HLBS diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .28

Compelling Questions & Critical Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29

Objective 6: Optimize clinical and implementation research to improve health and reduce disease . . . . . . . . . . . . . . . .36

Compelling Questions & Critical Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37

Objective 7: Leverage emerging opportunities in data science to open new frontiers in HLBS research . . . . . . . . . . . 41

Compelling Questions & Critical Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42

Objective 8: Further develop, diversify, and sustain a scientific workforce capable of accomplishing 

the NHLBI’s mission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45

Compelling Questions & Critical Challenges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .50

Contents
2 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Director’s Message

The National Heart, Lung, and Blood Institute (NHLBI) began the Strategic 

Visioning process with a bold challenge: Imagine a world where we are able to 

prevent the burden of cardiovascular, lung, and blood diseases; a world where 

we are able to capture the promise of personalized precision medicine, with each 

person receiving the right treatment, tailored to his or her needs, at the right time.

Through a dynamic and iterative process, we engaged diverse stakeholders 

from across the United States and around the globe (figure 1) and received an 

unprecedented number of ideas that have informed the development of this 

Strategic Vision. The research priorities in this Strategic Vision will enable us to 

accelerate our journey toward scientific and health advances over the next decade. 

This is an exciting time for behavioral and biomedical research. The convergence of innovations in areas such as computational biology, data science, 

bioengineering, and high-throughput “omic” technologies holds promise for 

Figure 1: Global Participation in Strategic Visioning

Participants came from 50 states and 42 countries. Registered Users on the Strategic Visioning Forum: 4,450; Ideas Supported: 42,000
 THE NHLBI STRATEGIC VISION | 3

major leaps forward in our understanding, at the most fundamental level, of human systems in both 

health and disease. With these developments and the help of our community, we have the opportunity to create a future in which we have an improved understanding of the complex interplay of 

environmental, behavioral, and molecular factors that promote health; a clearer picture of the earliest 

point of disease development; the ability to repair defective or damaged hearts with stem cell and 

tissue engineering techniques; a new generation of novel therapeutics for chronic conditions such as 

chronic obstructive pulmonary disease, heart failure, pulmonary fibrosis, hypertension, and asthma; 

and the ability to develop cures, through gene editing and stem cell technology, for sickle cell disease 

and other conditions. 

The NHLBI will implement the Strategic Vision by developing specific activities and initiatives that 

are inspired by the strategic research priorities. We will leverage the research priorities for broad 

impact. Even if a particular disease or health concern is not cited by name, the scientific initiatives that 

emerge will be both crosscutting and targeted to ensure that we address pressing health concerns and 

conditions across our portfolio. In addition, investigator-initiated ideas will remain the principal way we 

support science. The ideas in this Strategic Vision are not intended to restrict or stifle creativity; rather, 

we hope that they stimulate and inspire scientists who are pursuing investigator-initiated ideas.

Strategic Visioning will remain a “living” process. As the NHLBI moves forward with implementation, 

our engagement with the community will continue. We will continue to foster ongoing dialogue through 

different forums, including webinars and workshops, to solicit and incorporate in our research program 

the best ideas of our community while keeping our strategic research priorities nimble and adaptive to 

scientific advancements and opportunities. 

The NHLBI is grateful for all the input received to help develop this Strategic Vision. I look forward to 

working with you and welcome comments on all that we do together. 

Sincerely,

Gary H. Gibbons, M.D.

Director, NHLBI
4 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Introduction

For more than 60 years, the NHLBI community has fostered a legacy of 

research excellence through groundbreaking fundamental discovery science, 

landmark clinical trials and population-based cohort studies, and innovative 

health education and dissemination efforts. Despite the significant advances 

in treatment and prevention made during these decades, heart, lung, blood, 

and sleep (HLBS) diseases still pose a major health and economic burden on 

the United States. Through its broad research portfolio, the NHLBI is tasked 

with combating not only the major causes of death and disability but also rare 

disorders such as sickle cell disease, thalassemia, and pulmonary fibrosis. While 

these disorders are rare in the overall population, the burdens they place on those 

affected are enormous.

In order to sustain the NHLBI’s legacy, we must anticipate and capitalize on 

emerging scientific opportunities, as well as foresee and identify approaches 

to overcome new barriers to progress. Strategic Visioning is a process that 

was initiated in recognition of these needs and in acknowledgment of the 

transformational scientific advances that are emerging at an accelerating pace. 

New scientific tools and an explosive expansion of 

the capacity to manage and analyze data present 

opportunities that are only limited by human 

imagination. Therefore, this is an especially 

opportune time for the NHLBI to partner with its 

scientific and patient communities to identify areas 

where the Institute can help others harness new 

opportunities and overcome roadblocks to scientific 

success. Many of our research goals that once seemed 

remote are now within reach. For example, in the next 

decade, preventable cardiovascular disease deaths 

for all age groups could decline more than 30 percent 

with the greater adoption of proven prevention and 

treatment strategies. A stroke-free era for children 

worldwide with sickle cell disease is now imaginable.

NHLBI Mission 

Statement

The National Heart, 

Lung, and Blood Institute 

(NHLBI) provides global 

leadership for a research, 

training, and education 

program to promote the 

prevention and treatment 

of heart, lung, and blood 

diseases and enhance the 

health of all individuals so 

that they can live longer 

and more fulfilling lives.

Investigatorinitiated ideas 

will remain the 

principal way we 

support science.
 THE NHLBI STRATEGIC VISION | 5

This Strategic 

Vision comprises 

over one hundred 

compelling 

questions and 

critical challenges 

aligned to eight 

scientific objectives.

The Strategic Vision is the culmination of an unprecedented effort to engage 

NHLBI’s communities in identifying and prioritizing the most compelling 

science for which NHLBI provides leadership. Over the next decade, these 

collective ideas could catalyze the closing of large gaps in knowledge and 

break through significant barriers to research progress in ways that adhere to 

the Institute’s enduring principles. This Strategic Vision comprises over one 

hundred compelling questions and critical challenges aligned to eight scientific 

objectives. The objectives, questions, and challenges cut across the entire 

NHLBI scientific portfolio.

A broad circle of partners participated in the Strategic Visioning process, 

including scientists, medical professionals, policymakers, patients and patient 

advocates, professional groups, and other interested members of the public. 

The Strategic Vision is unique in that, unlike a conventional strategic plan, it 

is dynamic and will be refreshed periodically with continuing input from the 

communities who are at the leading edge of scientific exploration and know the 

needs of our scientific and patient communities. The Strategic Vision is a “living” 

document, meaning it will 

be updated to respond to the 

changing needs of the HLBS 

research community. This will 

provide an ongoing source of 

scientific inspiration for NHLBIsolicited research programs and 

may also serve as inspiration 

for the scientific community at 

large.

NHLBI’s Enduring Principles

• Value investigator-initiated fundamental 

discovery science

• Maintain a balanced cross-disciplinary portfolio 

(basic, translational, clinical, population science)

• Train and nurture a diverse new generation of 

leaders for the biomedical workforce

• Support implementation science that empowers 

patients and enables partners to improve health

• Innovate an evidence-based elimination of 

health inequities in the United States and around 

the world
6 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Strategic Goals

The NHLBI launched the Strategic Visioning process with four mission-oriented 

strategic goals. These goals cut across the Institute’s HLBS research portfolio 

and are rooted in a desire to understand and promote health and resilience, 

stimulate discoveries in the causes of disease, enable the translation of discoveries 

from basic research into clinical practice, and foster training and mentoring of 

emerging scientists and physicians. 

UNDERSTAND HUMAN 

BIOLOGY

To expand knowledge of 

the molecular, cellular, and 

physiological mechanisms 

governing the normal function 

of HLBS systems as essential 

elements for sustaining 

human health.

REDUCE HUMAN DISEASE

To extend our knowledge of 

the pathobiology of HLBS 

disorders and enable clinical 

investigations that advance 

the prediction, prevention, 

preemption, treatment, and 

cures of human diseases.

DEVELOP WORKFORCE 

AND RESOURCES

To enable and develop 

a diverse biomedical workforce 

equipped with the 

essential research resources 

to pursue emerging 

opportunities in science.

ADVANCE TRANSLATIONAL 

RESEARCH

To facilitate innovation and 

accelerate research translation 

across the entire research 

spectrum, bridging basic to 

clinical, clinical to practice, and 

population to health impact.

The NHLBI Strategic Visioning crowdsourcing forum served as an interactive 

platform that allowed the NHLBI community to submit, vote, and comment on 
 THE NHLBI STRATEGIC VISION | 7

Compelling Questions and Critical Challenges that aligned with these four 

strategic goals (figure 2). These questions and challenges could also be addressed in 

5 to 10 years, with NHLBI facilitation. 

• Compelling Questions are unanswered questions or poorly understood areas 

of research requiring NHLBI facilitation because their complexity exceeds the 

capacity of any one investigator-initiated program.

• Critical Challenges are barriers or impediments to scientific progress, and 

overcoming these obstacles will result in significant impact.

With extensive input from the National Heart, Lung, and Blood Advisory Council 

and the Board of External Experts, a working group of Council, the NHLBI 

reviewed the submitted ideas and associated feedback and selected a set of 

Strategic Research Priorities (i.e., Compelling Questions and Critical Challenges) 

that resonated as high priorities for the Institute based on timeliness, feasibility, 

and potential to advance the fields of study. All submitted suggestions from the 

community have been retained and can be revisited as new opportunities or 

challenges arise as part of the dynamic Strategic Visioning process.

Figure 2: Strategic Visioning Participation

Compelling Questions (CQs)/Critical Challenges (CCs) Submitted: Breakdown by Goal

DEVELOP WORKFORCE AND 

 RESOURCES

UNDERSTAND HUMAN BIOLOGY

ADVANCE TRANSLATIONAL

RESEARCH

REDUCE HUMAN DISEASE

Total 

CQs/CCs

Submitted

1,234

As the NHLBI 

moves forward 

with Strategic 

Visioning 

implementation, 

our engagement 

with the 

community 

will continue.
8 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

4 GOALS 

8 OBJECTIVES

Strategic Objectives

The following eight objectives resulted from this collaborative process and provide 

a framework for the strategic research priorities submitted by the participants. The 

objectives reflect one or more of the mission-oriented strategic goals and generally 

explore both biological and non-biological contributors to health and disease.

Over the next decade, these objectives will serve as the NHLBI’s guide for 

moving heart, lung, blood and sleep science forward, exploring research 

opportunities, and making investment decisions. While these objectives are not 

meant to embody the NHLBI’s entire research portfolio, the strategic research 

priorities corresponding to the objectives will play a substantial role in helping 

the NHLBI to set, and periodically refine, a research agenda and priorities for the 

next decade. 

In the pages that follow, we elaborate on the objectives, explaining their 

importance and envisioning how achieving these aims could guide research and 

improve health.

1 Understand normal biological function 

and resilience

2

Investigate newly discovered pathobiological mechanisms important to the onset 

and progression of HLBS diseases

3

Investigate factors that account for 

differences in health among populations
 THE NHLBI STRATEGIC VISION | 9

4 mission-oriented goals are 

at the center of the Strategic 

Vision 

8 objectives provide a 

framework for moving 

HLBS science forward

4

Identify factors that account for individual 

differences in pathobiology and in 

responses to treatments

5

Develop and optimize novel diagnostic 

and therapeutic strategies to prevent, 

treat, and cure HLBS diseases

6

Optimize clinical and implementation 

research to improve health and 

reduce disease

7

Leverage emerging opportunities 

in data science to open new frontiers in 

HLBS research 

8

Further develop, diversify, and sustain 

a scientific workforce capable of 

accomplishing the NHLBI’s mission
10 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 1:

Understand 

normal 

biological 

function and 

resilience

10 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
 THE NHLBI STRATEGIC VISION | 11

STRATEGIC VISION 

OBJECTIVE 1

Understand normal biological function 

and resilience

Understanding normal biology is the backbone of all biomedical science. It is 

essential for understanding homeostatic maintenance, predicting how biological 

systems respond to their environment, and recognizing disease and targets for 

intervention. Research on normal biological function—including emerging topics 

such as circadian rhythms, the microbiome, and understanding how tissues 

develop from progenitor cells—can help us to better define health and understand 

the earliest origin of disease processes. The scope of research on normal biology 

can range from single cell analytics to studies of entire healthy populations. 

Using gold standard and emerging tools, methodologies, and technologies, such 

research can uncover the biological factors, behaviors, lifestyle factors, social 

circumstances, and environmental exposures that enable the resiliency essential 

for sustaining wellness in the face of the aging process, stressors, and adverse 

influences. Gaining new knowledge about the body’s intrinsic reparative capacity 

will yield greater insight into the transition from health to disease. For these 

reasons, understanding normal biology must remain a cornerstone of NHLBIfunded research.

Envision a future in which we are able to...

• Promote resilience and healthy aging through the application of normal 

and reparative biology using cells (e.g., progenitor cells) that enable the 

regeneration and repair of heart, lung, blood, and sleep systems. 

• Use emerging nanoscale imaging technologies (e.g., cryo-electron 

microscopy) and single-cell analytics to characterize the molecular 

signature of the homeostatic state of HLBS systems that sustain health and 

wellness. 

• Generate a better understanding of how environmental exposures, social 

determinants, and behaviors (e.g., diet and physical activity) modulate 

biological systems such as the epigenome, microbiome, and immune system 

to sustain health and promote resilience.
12 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 1:

Understand 

normal 

biological 

function and 

resilience

Objective 1 Compelling Questions

1.CQ.01 How are normal cell functions regulated by complex gene networks and cellto-cell interactions?

1.CQ.02 What are the key molecular and structural mechanisms that allow single 

cells and tissues to sense, integrate, and respond to mechanical cues and 

influences at local and systemic levels?

1.CQ.03 What are the molecular, developmental, hormonal, and behavioral 

mechanisms and psychological, social, and environmental factors—evaluated 

with a systems biology approach—involved in maintaining healthy weight 

across the lifespan?

1.CQ.04 What are the mechanisms and range of normal physiologic responses to 

environmental, neuropsychiatric, social, and other stimuli that predict 

homeostatic resilience or transition to disease across the lifespan?

1.CQ.05 What innate and adaptive immune system mechanisms promote HLBS health 

and prevent development of HLBS diseases?

1.CQ.06 How do specific lymphatic immune and nonimmune circulatory functions 

interact with and contribute to HLBS health and resilience?

1.CQ.07 What is the influence of the microbiome (including virome and fungome) 

on the immune system and on HLBS health and resilience, including 

developmental processes, across the lifespan?
 THE NHLBI STRATEGIC VISION | 13

Objective 1 Compelling Questions

1.CQ.08 What are the basic pathways underlying the effects of circadian function, 

synchronization, and harmonization on HLBS health and resilience across the 

lifespan?

1.CQ.09 Does circadian regulation modify the effects of environmental exposures 

(e .g ., cigarette smoke, particulates, pathogens, temperature, humidity) on 

mechanisms of HLBS function?

1.CQ.10 What are the mechanisms that underlie adaptation in HLBS systems in 

extreme conditions, and how can this knowledge be used to develop novel 

interventions that optimize health or prevent disease?

1.CQ.11 What are the basic mechanisms that direct the interactions of blood cells with 

each other and their environment, how do these interactions influence their 

function, and how can this understanding be used to optimize the handling of 

blood cells?

1.CQ.12 What are the normal molecular and cellular variations in specific regions of 

the lung, and what controls these variations?

1.CQ.13 What “omic” signatures describe the normal vasculome (gene expression 

patterns in the vascular endothelium) of the different vascular beds and 

different arteries (elastic vs . muscular) that supply HLBS tissues and organs?
14 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Objective 1 Critical Challenges

1.CC.01 Reliable and diverse investigational models—from single cells to animals—

that reflect individual variation as well as sex/gender-based differences are 

needed to reproduce normal functioning of HLBS systems and to reflect the 

activities of molecular targets in those systems and related diseases .

1.CC.02 Standardized protocols are needed to establish and maintain cultured 

cell lines relevant to functional studies of HLBS systems . Specifically, 

facilitating the availability of hard-to-culture cell lines and cells from female 

research subjects, expanding the number of HLBS cell lines, and improving 

reproducibility across studies are necessary .

1.CC.03 Development and application of comprehensive single-cell biology analytics 

are needed to facilitate an integrated understanding of cellular diversity, cellcell interactions, and cellular phenomena in HLBS health and disease risk .

1.CC.04 Advances in methods of and models for assessing and characterizing 

exposures (e .g ., environmental, dietary, social) are needed to improve 

research on normal biologic function and resilience .

1.CC.05 Gaining fundamental knowledge of the glycome, its regulation, and its 

function in HLBS systems is needed to improve understanding of posttranslational modifications of proteins .

1.CC.06 Dietary assessment methodologies that combine objective measures and 

biomarkers of dietary intake are needed to identify dietary patterns and food 

constituents that contribute to healthy weight maintenance and to inform 

intervention strategies to lower cardiometabolic risks .

1.CC.07 New investigative tools and knowledge of structural and matrix biology are 

needed to better understand injury, regeneration, and repair of the normal 

(or developing) heart, lung, and blood tissues and to enable regenerative 

medicine .

STRATEGIC VISION 

OBJECTIVE 1:

Understand 

normal 

biological 

function and 

resilience
 THE NHLBI STRATEGIC VISION | 15

STRATEGIC VISION 

OBJECTIVE 2:

Investigate 

newly discovered 

pathobiological 

mechanisms 

important to the 

onset and progression 

of HLBS diseases

 THE NHLBI STRATEGIC VISION | 15
16 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 2

Investigate newly discovered pathobiolog- ical mechanisms important to the onset 

and progression of HLBS diseases

Discovering new pathobiological mechanisms and understanding them is critical 

for improving HLBS health. Such discoveries and research can potentially lead 

to clinical and implementation studies, which in turn can inform new therapeutic 

strategies and clinical practice. Important areas to focus on, with the help of 

emerging technologies such as molecular imaging and nanotechnology, include 

mechanisms involved in the pathogenesis of rare and common diseases, diseaserelated structural and functional changes, and the clinical significance of these 

changes. In addition, tracking of disease onset and progression across the 

lifespan is essential because it has the potential to inform our understanding of 

the conversion of chronic conditions into acute disease and the effects of early 

exposures and interventions, including lifestyle changes.

Envision a future in which we are able to...

• Preempt the transition from health to disease and enable primary 

and secondary prevention through an enhanced understanding of the 

pathobiological mechanisms underpinning HLBS disorders.

• Leverage deep phenotyping and high-throughput “omic” technologies 

in NHLBI-supported cohort studies to define the functional significance 

of gain/loss-of-function genetic variants and gene knockouts on human 

pathobiology and the clinical outcomes of HLBS disorders.

• Gain new insights into modifier genes 

and molecular pathways that influence 

the clinical manifestations and severity 

of monogenic disorders (e.g., sickle cell 

disease and cystic fibrosis) as well as 

structural defects such as congenital 

heart disease, and thereby catalyze new 

therapeutic strategies.
 THE NHLBI STRATEGIC VISION | 17

Objective 2 Compelling Questions

2.CQ.01 What are the molecular mechanisms underlying dysregulation of homeostasis, and how do these mechanisms vary from individual to individual, leading 

to development of HLBS diseases in some but not in others?

2.CQ.02 What are the roles of RNAs (e .g ., microRNAs, long non-coding RNAs) in 

HLBS systems’ growth, adaptation, and injury-repair responses?

2.CQ.03 What biomarkers of acute and chronic environmental exposures (e .g ., 

smoking) are predictive of disease onset or progression? What biologic 

effects measured by these biomarkers are irreversible responses and which 

are opportunities for intervention?

2.CQ.04 How do endogenous stem/progenitor cells and defects in these cells 

contribute to the onset and progression of chronic HLBS diseases?

2.CQ.05 What is the pathobiology of aberrant calcification of coronary arteries, heart 

valves, and peripheral arteries, and why is calcification associated with a 

poor prognosis?

2.CQ.06 What interdependencies between the brain/peripheral nervous system and 

the heart/vascular systems are important to the development, progression, 

manifestations, and treatment of cardiac and vascular disease?

2.CQ.07 What are the mechanisms whereby social conditions and psychosocial stress 

contribute to the onset, progression, and morbidity of ischemic heart disease 

and peripheral arterial disease?

2.CQ.08 What are the mechanisms whereby congestive heart failure causes lung 

remodeling and leads, in end-stage disease, to right ventricular failure?

2.CQ.09 What pathobiology underlies vascular causes of cognitive decline? 

What early interventions could target this pathobiology to maintain 

cognitive function?
18 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Objective 2 Compelling Questions

2.CQ.10 What is the pathobiology of fibrosis that accounts for its organ specificity 

(often affecting the lungs, heart, or bone marrow alone), its progression in the 

absence of apparent stimuli, and its resistance to drug therapy?

2.CQ.11 What is the pathophysiology of heart failure with preserved ejection fraction 

(HFpEF), and how can this condition be better diagnosed and treated?

2.CQ.12 What is the relationship between

angiogenesis and placental 

function in at-risk pregnancies?

2.CQ.13 How can a better understanding of the molecular and physiological 

mechanisms of hypothermia help differentiate beneficial hypothermia from 

uncontrolled shock-induced hypothermia?

Objective 2 Critical Challenge

2.CC.01 Understanding the pathobiologic mechanisms that govern the conversion of 

chronic HLBS conditions into acute disease is critically needed, specifically 

identifying biomarkers to predict and therapies to prevent these transitions .

STRATEGIC VISION 

OBJECTIVE 2:

Investigate 

newly discovered 

pathobiological 

mechanisms 

important to the 

onset and progression 

of HLBS diseases
 THE NHLBI STRATEGIC VISION | 19

STRATEGIC VISION 

OBJECTIVE 3:

Investigate 

factors that account 

for differences 

in health among 

populations

 THE NHLBI STRATEGIC VISION | 19
20 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 3

Investigate factors that account for 

differences in health among populations 

Variations exist between populations—grouped by such factors as age, sex, race, 

and ancestry—in susceptibility and resilience to HLBS diseases and in disease 

course and outcomes. While some of these variations are caused by genetic and 

other biological factors, a wide range of behavioral factors and socioeconomic 

inequities also contribute to health disparities. Research is needed to better 

understand the causes of population health differences and to identify strategies 

to effectively address these differences. Investigations in this area may range 

from basic laboratory studies to population science to community-centered 

implementation research.

Envision a future in which we are able to...

• Leverage a deeper understanding of biologic differences related to sex or 

ancestral groups (e.g., variation in ancestry leading to differences in asthma 

phenotypes among ethnic subgroups) to devise more precise, targeted 

intervention strategies and further improve clinical outcomes. 

• Reduce health disparities 

and inequities in an era of 

information technology by 

leveraging epidemiology and 

the power of data science to 

understand and solve complex 

health problems.
 THE NHLBI STRATEGIC VISION | 21

Objective 3 Compelling Questions

3.CQ.01 What community-based effectiveness and implementation research 

strategies can help address HLBS health inequities?

3.CQ.02 How can we improve the representation of women, minority, and 

disadvantaged populations in clinical research studies and ensure that 

findings are applicable to these populations?

3.CQ.03 What are the environmental, 

genetic, and epigenetic factors and 

molecular, cellular, and systemic 

mechanisms that determine sexrelated differences in HLBS health 

and disease?

3.CQ.04 Do the factors that render individuals or populations subjected to the same 

exposures (e .g ., diet, smoking, other environmental and social exposures) 

resilient or susceptible to disease differ across the lifespan and by sex/

gender?

3.CQ.05 How can cardiometabolic risk be managed to improve health trajectories 

in specific populations (e .g ., according to race, ethnicity, sex/gender, 

socioeconomic status)?
22 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 3:

Investigate 

factors that account 

for differences 

in health among 

populations

Objective 3 Critical Challenges

3.CC.01 Sex/gender-specificity is needed in basic, translational, and clinical studies; 

data analyses; and management guidelines for HLBS conditions .

3.CC.02 Novel experimental strategies and tools are needed to evaluate the effect of 

sex differences on HLBS health, resilience, and disease .

3.CC.03 Integrated analysis of expanding collections of health information from 

individual patients—including genetic, epigenetic, and “omic” data—is needed 

to allow more precise medical management of patients at risk for or afflicted 

with an HLBS disorder, especially among groups that are understudied or 

have disparate morbidity and mortality (e .g ., minorities, women) .

3.CC.04 Advances in methods of and 

models for assessing and 

characterizing exposures 

(e .g ., diet, smoking, other 

environmental and social 

exposures) are needed to 

understand differences in 

health among populations .
 THE NHLBI STRATEGIC VISION | 23

STRATEGIC VISION 

OBJECTIVE 4:

Identify factors 

that account 

for individual 

differences in 

pathobiology and 

in responses 

to treatment

 THE NHLBI STRATEGIC VISION | 23
24 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 4

Identify factors that account for 

individual differences in pathobiology 

and in responses to treatments 

Research advances in areas such as genomics and other “omics” (e.g., 

proteomics, metabolomics) have provided new opportunities to deepen our 

understanding of HLBS pathobiological processes and how these vary among 

individual patients. Accelerating progress toward precise, individualized 

prevention efforts and medical interventions will require research into 

biological factors, environmental exposures, and other influences that account 

for differences in pathobiology and unique responses to treatment (including 

drug reactions and other adverse events). This research will allow personal 

and clinical decisions, practices, and medical products to be tailored to the 

individual patient to help optimize outcomes.

Envision a future in which we are able to...

• Develop precise clinical interventions based on individual environmental 

exposures, behaviors, genotypes, and molecular-cellular phenotypes. 

• Accelerate the incorporation of new 

imaging, omics, and sensor 

technologies with advanced data 

analytics to inform more precise 

clinical classification of chronic 

diseases (e.g., asthma, pulmonary 

fibrosis, chronic obstructive lung 

disease, heart failure) and thereby 

enable more accurate diagnosis 

and treatment.
 THE NHLBI STRATEGIC VISION | 25

Objective 4 Compelling Questions

4.CQ.01 Which phenotypic, biomarker, and molecular characteristics predict outcome 

and, when applied in clinical studies, predict differential responses to therapy 

in individuals and in different populations with HLBS diseases?

4.CQ.02 What factors render individuals or populations subjected to the same 

exposures (e .g ., diet, smoking, other environmental and social exposures) 

resilient or susceptible to disease?

4.CQ.03 What underlies secondary resilience, such that some people are protected 

from the complications of HLBS diseases?

4.CQ.04 Which patients benefit from rehabilitation treatments (e .g ., cardiac, vascular, 

and pulmonary), and how can the benefits of rehabilitation treatments be 

sustained long term?

4.CQ.05 How does the pathobiology that underlies nonobstructive ischemic heart 

disease and the associated risks for acute coronary syndrome and early 

mortality differ between subpopulations, and what are the targets for 

treatment and prevention?

4.CQ.06 What tests would identify individuals who are at high risk of venous 

thromboembolic events and would benefit from targeted risk factor 

modification and/or intensive prophylaxis?

4.CQ.07 What are biomarkers of pulmonary hypertension that could better identify 

individuals at high risk, reveal underlying mechanisms, and guide treatment?

4.CQ.08 What are the major determinants of individual and sex differences in 

breathing patterns in sleep, susceptibility to insomnia, and other sleep 

behaviors?

4.CQ.09 What genetic, biomarker, and environmental predictors of risk and outcome 

would inform and improve management of sickle cell disease and secondary 

prevention of its progression and complications?
26 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 4:

Identify factors 

that account 

for individual 

differences in 

pathobiology and 

in responses 

to treatment

Objective 4 Critical Challenges

4.CC.01 Predictive modeling and prevention trials are needed in populations at high 

risk for highly prevalent HLBS diseases .

4.CC.02 In patients with an aortic aneurysm, better tools are needed to determine 

which patient phenotypes and disease characteristics could best predict who 

would benefit from a repair . Examples of such tools include animal models 

that reflect human pathology and biomarkers/molecular imaging tools that 

are predictive of rupture or dissection .

4.CC.03 Clinical evaluation 

tools are needed 

to differentiate 

patients with 

atherosclerotic 

heart disease who 

will progress to 

myocardial 

infarction or 

with sudden 

cardiac death 

from those with 

stable disease .
 THE NHLBI STRATEGIC VISION | 27

STRATEGIC VISION 

OBJECTIVE 5:

Develop and 

optimize novel 

diagnostic and 

therapeutic 

strategies to prevent, 

treat, and cure 

HLBS diseases
28 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 5

Develop and optimize novel diagnostic 

and therapeutic strategies to prevent, 

treat, and cure HLBS diseases 

Recent scientific and technological developments offer especially promising 

opportunities to prevent disease, manage and treat illness, and promote resilience. 

These wide-ranging developments include, but are not limited to, new gene editing 

techniques that could safely treat and prevent HLBS diseases, “smart” tools that 

could monitor and adjust biological processes, techniques that modulate stem cell 

or immune system signaling to reduce disease risk, and advances in materials 

science that could yield vastly improved implant devices. Other technologies and 

bioengineering developments may further facilitate diagnostic capabilities, and new 

lifestyle interventions may improve the maintenance of continued health and wellness 

and facilitate behavioral modification to prevent disease. Many of these advances, 

which are the results of past investments in basic research, are critical to developing 

and optimizing novel diagnostics and therapeutics strategies.

Envision a future in which we are able to...

• Develop surgical grafts (using stem cells, 3-D printing, and 

nanotechnologies) for children born with heart defects, such that the 

grafts grow as the child grows into adulthood, thereby avoiding multiple 

operations. 

• Transform the safety and availability 

of the nation’s blood supply by using 

genetically engineered stem cells to 

eliminate histo-incompatibility 

antigens and generate universal 

donor red blood cells that are 

available off the shelf by a highthroughput process.
 THE NHLBI STRATEGIC VISION | 29

Objective 5 Compelling Questions

5.CQ.01 Would reduction of known 

cardiac and vascular risk 

factors during childhood and 

adolescence translate into 

the prevention or delayed 

development of atherosclerosis 

and other heart diseases?

5.CQ.02 Would interventions in pregnancy or early childhood designed to modulate 

immune development result in primary prevention of asthma?

5.CQ.03 How should the management of diseases that typically develop in childhood 

(including childhood interstitial lung disease, hemoglobinopathies, 

congenital heart disease, cystic fibrosis, and asthma) be modified as affected 

individuals mature into adulthood?

5.CQ.04 Would using multidisciplinary teams (e .g ., nutritionists, exercise 

physiologists, social workers, psychologists, nurses) be an effective 

approach to developing, testing, and ultimately applying lifestyle 

interventions as part of routine patient care in a variety of contexts from 

community to patient care settings?

5.CQ.05 Would circadian-based strategies (e .g ., sleep, timing of medication, meals) 

improve the efficacy of treatments for HLBS diseases (e .g ., hypertension, 

asthma, thrombosis, obesity/diabetes)?
30 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Objective 5 Compelling Questions

STRATEGIC VISION 

OBJECTIVE 5:

Develop and 

optimize novel 

diagnostic and 

therapeutic 

strategies to prevent, 

treat, and cure 

HLBS diseases

5.CQ.06 What technical improvements in the collection, preparation, storage, and 

processing of blood products would improve their potency, safety, and 

lifetime? What biomarkers or other characteristics predict stability during 

storage and successful transfusion?

5.CQ.07 What effective and implementable practices (e .g ., 

recognition and initial response by the community, 

emergency medical response, hospital-based care) 

would reduce the rate of mortality associated with 

out-of-hospital cardiac arrest?

5.CQ.08 How can real-time, individual-level monitoring be used to detect and predict 

electrical instability of the heart and reduce risk for sudden cardiac death in 

low-risk patients?

5.CQ.09 What is the optimal clinical management approach for patients with severe 

calcific aortic stenosis but with minimal symptoms?

5.CQ.10 What is the best strategy for reducing cardiac and vascular morbidity 

and mortality in cancer survivors who are at enhanced risk of cardiac 

and vascular events and whose clinical care may be complicated by both 

comorbidities and drug toxicity?
 THE NHLBI STRATEGIC VISION | 31

Objective 5 Compelling Questions

5.CQ.11 In patients with enhanced cardiovascular risk due to comorbidities from 

chronic diseases (e .g ., HLBS disorders, diabetes) and multiple drug therapy, 

what is the best strategy for reducing cardiac and vascular morbidity and 

mortality?

5.CQ.12 What are the optimal red blood cell transfusion thresholds and optimal 

plasma transfusion strategies in both pediatric and adult patients?

5.CQ.13 How can we optimize the effectiveness and safety of allogeneic 

hematopoietic stem cell transplantation in the treatment of nonmalignant 

blood and immune disorders and prevent both short-term and long-term 

complications?

5.CQ.14 What are the mechanisms for the late development of complications after 

hematopoietic stem cell transplantation ? How can these consequences be 

predicted and prevented to reduce the high rates of mortality following HSCT?

5.CQ.15 How can we “reprogram” the immune system to improve outcomes of 

allogeneic cell therapies, tissue and organ transplants, and regenerative 

strategies and to diminish allogeneic responses to essential biologic 

replacement therapies?

5.CQ.16 How can improved methods for hematopoietic cell transplantation or gene 

therapy approaches be used to cure certain hemoglobinopathies (e .g ., sickle 

cell disease)?

5.CQ.17 How do we develop and implement novel strategies to prevent and treat 

minor and major hemorrhagic complications in males and females affected 

by acquired and inherited disorders?
32 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 5:

Develop and 

optimize novel 

diagnostic and 

therapeutic 

strategies to prevent, 

treat, and cure 

HLBS diseases

Objective 5 Compelling Questions

5.CQ.18 Is targeted manipulation of epigenetic modifications (distinct from global 

suppression of histone acetylation or DNA methylation) a useful strategy for 

therapeutic intervention in chronic cardiopulmonary or blood diseases?

5.CQ.19 With increasing use of direct-acting oral anticoagulants for stroke prevention 

in atrial fibrillation and treatment of venous thromboembolism, what is the 

role of laboratory monitoring, and can the use of new technologies help better 

define those at risk of bleeding or thrombosis with use of direct-acting oral 

anticoagulants or warfarin?

5.CQ.20 How can imaging technology be leveraged to identify clinically useful 

markers of metabolic syndrome and cardiopulmonary disease?

5.CQ.21 Do interventions to improve ventilation during sleep decrease morbidity and 

mortality in individuals with either heart failure (or other diseases associated 

with chronic hypoxemia) and sleep-disordered breathing?

5.CQ.22 How can alterations of stem cell cycles and other therapies, as well as 

endogenous mechanisms, be harnessed to promote repair and regeneration of 

the heart, lung, and blood systems?

5.CQ.23 How can we better integrate 

palliative care concepts, such 

as respect for personal values, 

goals, and treatment preferences, 

in the management of patients 

with HLBS diseases?
 THE NHLBI STRATEGIC VISION | 33

Objective 5 Critical Challenges

5.CC.01 A better understanding of the factors governing the safety and efficacy of 

therapeutic hemoglobin-based extracellular oxygen carriers (HBOCs) and 

improved animal models for HBOC studies are needed .

5.CC.02 An understanding of the immune system from a systems biology 

perspective is needed to design more efficacious treatment strategies for 

chronic inflammatory and autoimmune HLBS diseases .

5.CC.03 Improved capabilities for responding rapidly and effectively to emerging 

infectious threats to the safety and availability of the nation’s blood supply 

are needed .

5.CC.04 Robust tools and algorithms are needed to evaluate objective biomarkers of 

sleep health and dysfunction .

5.CC.05 New materials and constructs that are electrically, chemically, and 

mechanically active are needed to enable the development of self-adjusting 

bioengineered implants (e .g ., self-regenerating protective layers, biologics 

like vein grafts, glucose-responsive polymers that release insulin) .

5.CC.06 Development of safe, well-functioning designer platelets and red blood cells 

from stem or progenitor cells, as well as the large-scale production of these 

products, is needed for therapeutic and diagnostic uses .

5.CC.07 Expanded research on bleeding risk in elderly patients with atrial fibrillation 

is needed to develop more accurate risk stratification that would enhance 

anticoagulation decision-making for the elderly population and reduce 

stroke incidence .
34 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Objective 5 Critical Challenges

STRATEGIC VISION 

OBJECTIVE 5:

Develop and 

optimize novel 

diagnostic and 

therapeutic 

strategies to prevent, 

treat, and cure 

HLBS diseases

5.CC.08 Clinical evaluation tools, such as biomarkers of physiologic age and 

a clinical score for frailty, are needed for assessing cardiopulmonary 

perioperative risk and predicting postoperative recovery in the elderly .

5.CC.09 Better apheresis-based sickle cell disease treatments are needed to provide 

the benefits of blood transfusion without the risks and complications that 

are associated with both simple and exchange transfusions .

5.CC.10 A variety of “smart” devices are 

needed that both monitor 

physiology and assist, adjust, or 

intervene automatically to treat 

acute complications of cardiovascular disease .

5.CC.11 A new generation of ventricular assist devices is needed to minimize 

platelet activation, thrombogenesis, and bleeding; to incorporate better 

percutaneous and transcutaneous systems; and to improve battery and 

charging-mechanism designs .

5.CC.12 More rapid translation of new discoveries about molecular, cellular, and 

tissue-based mechanisms of arrhythmia into better therapeutic and 

preventive strategies is needed .
 THE NHLBI STRATEGIC VISION | 35

STRATEGIC VISION 

OBJECTIVE 6:

Optimize 

clinical and 

implementation 

research to 

improve health 

and reduce 

disease
36 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 6

Optimize clinical and 

implementation research to improve 

health and reduce disease

New methodologies, research frameworks, and resources need to be developed 

to refine the conduct of clinical studies and implementation research, while also 

improving the overall efficiency and effectiveness of the research enterprise. 

Current challenges include difficulties in recruitment of research participants 

and effective translation of knowledge gained from these studies into programs 

and policies that improve health at the clinic and community levels.

Envision a future in which we are able to...

• Use novel platforms that link electronic health records and personal health 

data to facilitate the identification and enrollment of participants in clinical 

research and empower research volunteers to self-identify. 

• Accelerate the translation of discovery into practice by embedding HLBS 

research platforms (e.g., clinical epidemiology registries, clinical trial 

networks, and implementation 

science programs) within 

“learning” health care systems, 

thereby engaging the clinical 

care and patient communities; 

leveraging electronic health 

records, patient registries, and 

existing datasets; and creating 

an integrative interface 

between clinical research 

and practice.
 THE NHLBI STRATEGIC VISION | 37

Objective 6 Compelling Questions

6.CQ.01 What methods and 

technologies are effective 

for increasing awareness of and participation 

in clinical research, as 

well as awareness of and 

access to evidence-based 

diagnostics and therapeutics, including emerging 

approaches to care?

6.CQ.02 What clinical trial designs are best for studying the chronobiology of drug 

delivery?

6.CQ.03 How can we engage relevant stakeholders, including patients, private 

entities, and federal agencies, to improve the clinical research enterprise 

and address critical needs such as standardized informed consent and cost 

containment?
38 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 6:

Optimize 

clinical and 

implementation 

research to 

improve health 

and reduce 

disease

Objective 6 Critical Challenges

6.CC.01 Synergy and collaboration among people at the MD and PhD level for; 

basic science; translational, patient-oriented researchers; community 

and population scientists; and individuals from multiple disciplines (e .g ., 

engineers, clinicians, subspecialists, generalists, bioinformatics experts, 

academics, nonprofit organizations, industry) are needed to enhance and 

expedite advances in 

HLBS research .

6.CC.02 Improvements in clinical trial design, population estimations, project 

management, and other practices are needed to achieve timely trial 

completion .

6.CC.03 Skills development and training are needed to improve the navigation of 

pre-clinical new drug phases of translational science .

6.CC.04 Innovative approaches to private sector collaborations and partnerships are 

needed early in therapeutic and diagnostic product development to bridge 

the gap between academic discoveries and product commercialization .

6.CC.05 Expanded resources for identifying therapeutic targets and agents, 

establishing proof of concept, and developing data for investigational new 

drug applications are needed to enable the early translation of research 

findings to clinical applications .

6.CC.06 Creative use of the array of newly available data sources is needed in clinical 

trial design and conduct in order to improve efficiency, cost effectiveness, 

and generalizability .
 THE NHLBI STRATEGIC VISION | 39

Objective 6 Critical Challenges

6.CC.07 Creative approaches to clinical trials in rare HLBS diseases are needed to 

successfully test strategies that will expand preventive and therapeutic 

options .

6.CC.08 Standardized approaches and resources, including data and biospecimen 

repositories, should be developed to facilitate collaboration between basic, 

clinical, and population scientists in clinical trials and population studies .

6.CC.09 Creative approaches are needed to effectively transcend silos (e .g ., 

perinatal, pediatric, and adult divides in clinical and translational research) .

6.CC.10 Novel methodologies and improvements in existing methodologies are 

needed for implementation research that explores uptake of research 

findings into approaches, programs, and policies .

6.CC.11 Multidisciplinary, multinational 

partnerships are needed to develop 

effective and sustainable strategies for combating chronic HLBS 

disorders in developing nations, 

which take into account the highly 

variable local epidemiology of 

HLBS disorders, the need for novel 

approaches to reducing disease 

burden, and the challenges of 

implementation in developing 

countries .
40 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 7:

Leverage 

emerging 

opportunities 

in data science 

to open new 

frontiers in 

HLBS research
 THE NHLBI STRATEGIC VISION | 41

STRATEGIC VISION 

OBJECTIVE 7

Leverage emerging opportunities in 

data science to open new frontiers 

in HLBS research 

New technologies, from “omics” platforms to high-throughput screening, have 

generated vast amounts of data that have the potential to provide new insights into 

the preemption and precise treatment of HLBS disorders. Unfortunately, only a small 

portion of these data are being optimally assessed and incorporated into practice. 

Developing innovative approaches to the integration, analysis, and interpretation of 

data from multiple sources will be essential. This information can then be effectively 

used to understand biological, social, and behavioral determinants associated with 

HLBS health and disease and to improve patient outcomes.

Envision a future in which we are able to...

• Empower heart failure patients and their health care providers to comanage care by using smartphone apps with personalized treatment 

algorithms that integrate electronic health record data, medication use 

monitors, and personal sensor data (e.g., body weight, heart rhythm, 

fluid balance) to sustain optimal function and quality of life. 

• Accelerate the discovery of mediators 

of health and disease through the seamless and shared use of readily 

accessible cloud-based datasets that integrate genomics and other omics 

analyses with carefully phenotyped research participant data from

 diverse sources. 

• Develop handheld devices to process and integrate genomics, clinical, 

and personal health data at the bedside to assist clinicians in their care 

of patients.
42 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 7:

Leverage 

emerging 

opportunities 

in data science 

to open new 

frontiers in 

HLBS research

Objective 7 Compelling Question

7.CQ.01 How do we encourage training in biostatistics, computer science, and 

bioinformatics to reach the entire biomedical community in this era of very 

large data sets?

Objective 7 Critical Challenges

7.CC.01 The development, application, 

and sharing of robust and 

multidimensional data-analytical and 

theoretical methods, mathematical 

modeling, and computational 

simulation techniques are needed 

for understanding fundamental 

mechanisms of HLBS systems, 

including gene, protein, and 

metabolic regulatory networks 

and the impact of environmental 

exposures on those networks .

7.CC.02 Novel integrative systems biology and analytical approaches are needed 

to exploit the wealth of knowledge coming from genetics, epigenetics, 

transcriptomics, metabolomics, proteomics, environmental exposures, 

electronic health records, and imaging to define disease subtypes, predict 

risks, and identify therapeutic targets .
 THE NHLBI STRATEGIC VISION | 43

Objective 7 Critical Challenges

7.CC.03 Novel analytical approaches, coordinated access to data, well-planned 

sample analyses, and creation of a scientific data commons are needed to 

leverage existing deeply phenotyped cohorts to accelerate translational 

research and promote the discovery of key druggable targets and the 

development of novel and precise treatments for HLBS diseases .

7.CC.04 Advancements are needed in the organization, infrastructure, 

integration, and availability of “omics” data, including genetic, epigenetic, 

transcriptomic, metabolomic, proteomic, phenotypic, and ontologic 

information .

7.CC.05 Bold new bioinformatic and biostatistical methods and approaches are 

needed to improve the analysis of big data .

7.CC.06 Creative and innovative methods to integrate and analyze data from 

population and cohort research are needed to generate hypotheses and to 

expedite bedside-to-basic “reverse translation .”

7.CC.07 Integration of registry data and research datasets is needed to facilitate 

research on the molecular genomics and pathobiology of congenital heart 

disease, including the natural history of congenital heart disease across the 

lifespan .

7.CC.08 Integration of multidimensional data from a variety of sources (e .g ., 

molecular, social, behavioral, environmental exposures, wearable sensor, 

self-reported data) is needed to develop predictive and actionable models of 

weight gain, weight loss, and weight loss maintenance and to clarify the role 

of obesity in the risk, prevention, and treatment of cardiopulmonary and 

sleep disorders .
STRATEGIC VISION 

OBJECTIVE 8:

Further develop, 

diversify, and 

sustain a scientific 

workforce capable 

of accomplishing 

the NHLBI’s 

mission

44 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
 THE NHLBI STRATEGIC VISION | 45

STRATEGIC VISION 

OBJECTIVE 8

Further develop, diversify, and sustain 

a scientific workforce capable of 

accomplishing the NHLBI’s mission

New approaches are needed to ensure the continuing development of a diverse 

scientific workforce equipped with the relevant skills, knowledge, and resources 

to tackle future HLBS challenges. This goal will require strategic interventions 

all along the research career continuum, including K to 12 education, collegiate 

and postdoctoral studies, and career development from early investigator to 

senior scientist. While this is relevant in all areas of development, particular 

attention is warranted for under-represented groups in science. Collaborative 

partnerships will be critical to collectively work toward the challenge of expanding 

the exposure of young students to the wonders of science and sustain that interest 

through college and graduate education. It is also critical to embrace research 

training as a lifelong exploration of scientific curiosity in which the NIH promotes 

the adoption of new disciplines, tools, and technologies as the scientific and public 

health landscape continually undergoes dynamic change.

Envision a future in which we are able to...

• Enable innovative solutions to pressing health 

problems by promoting the development 

of multidisciplinary teams capable of 

leveraging diverse skills and perspectives 

from crosscutting research fields such as data 

science, computational biology, quantitative 

population sciences, behavioral science, and 

implementation science.
46 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 8:

Further develop, 

diversify, and 

sustain a scientific 

workforce capable 

of accomplishing 

the NHLBI’s 

mission

Objective 8 Compelling Questions

8.CQ.01 What kinds of exposures, beginning in early education, would stimulate and 

maintain students’ interest in and understanding of science, particularly 

students from diverse and disadvantaged backgrounds?

8.CQ.02 How can we foster diversity among trainees and in the HLBS scientific 

workforce so that our research community reflects the makeup of the 

population at large and has ample participation of individuals from 

disadvantaged and medically underserved communities?

8.CQ.03 How can clinical research training programs increase cultural competency 

about diseases or conditions that disproportionately affect underserved 

populations and attract and retain researchers who better understand the 

populations affected?

8.CQ.04 What are the best strategies to develop a highly competent and diverse 

scientific workforce—across the spectrum from basic to population 

science—to address domestic and international health inequities?

8.CQ.05 How do we ensure that HLBS trainees across the career continuum 

are aware of and prepared for a variety of possible scientific career 

opportunities (e .g ., careers in teaching, industry, government)?

8.CQ.06 How do we best develop a scientific workforce that is fluent in product 

development and commercialization issues, including regulatory, 

intellectual property, and business issues, in order to bring products for 

HLBS indications to the market?
 THE NHLBI STRATEGIC VISION | 47

Objective 8 Compelling Questions

8.CQ.07 How do we attract more students/trainees into traditional research fields 

(e .g ., physiology, integrative biology) that are as critical to advancing 

science as emerging fields (e .g ., “omics,” big data), but do not have the same 

cache and are thus on the decline?

8.CQ.08 How do we add communication skills to our training programs to improve 

scientists’ communication with the public? How do we also improve the 

ability of basic and clinical scientists to understand each other’s scientific 

language and appreciate the importance of the other’s research questions 

and findings?

8.CQ.09 How can we harness virtual learning technologies (e .g ., immersive learning 

simulations, serious games) to address the needs of the modern and future 

biomedical workforce?

8.CQ.10 How can we better incorporate interdisciplinary and team science in 

our training and career development programs to prepare scientists for 

collaborative research and for using emerging technologies and resources?

8.CQ.11 How can senior scientists be 

encouraged to mentor young 

investigators and, in the 

later stages of their career, to 

entrust greater responsibility 

to emerging lab leaders (e .g ., 

incrementally turning over 

their projects to more junior 

lab members)?
48 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STRATEGIC VISION 

OBJECTIVE 8:

Further develop, 

diversify, and 

sustain a scientific 

workforce capable 

of accomplishing 

the NHLBI’s 

mission

Objective 8 Critical Challenges

8.CC.01 Sufficient numbers of clinical scientists are needed, particularly those 

interested in pursuing translation of breakthroughs from basic science 

laboratories into clinical settings .

8.CC.02 Programs of training, professional development, and mentoring are 

needed to help create a more diverse cadre of senior leaders in science and 

medicine .

8.CC.03 Methods for encouraging medical students to choose research career paths 

are needed .

8.CC.04 Training that emphasizes rigorous scientific methods in the biomedical, 

behavioral, and social sciences is required to increase reliability and 

reproducibility of research findings .

8.CC.05 Better preparation of scientists for transitions between career stages (e .g ., 

the graduate/medical education stage, the postdoctoral/fellowship period, 

the junior investigator stage) is needed .

8.CC.06 There is a need to develop and improve skills to communicate science to the 

public as well as among scientists of different specialties .

8.CC.07 Curricula and resources for education of health care workers in evidencebased care are needed .

8.CC.08 Collection and analysis of education and employment data from HLBS 

scientists over the course of their careers is needed to define metrics and 

predictors of success at both individual and training-program levels .
 THE NHLBI STRATEGIC VISION | 49
50 | NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Conclusion

Investigator-initiated discovery science has been and will remain the bedrock 

of the NHLBI mission, and individual researchers will always be encouraged 

to pursue their ideas through investigator-initiated projects. However, NHLBI 

leadership can catalyze extramural investigations that take advantage of new 

scientific opportunities and close gaps in knowledge. One means by which 

this occurs is through Institute-solicited research initiatives supported by new 

Funding Opportunity Announcements (FOAs). The Strategic Research Priorities 

identify important opportunities in science that will shape the development of 

future FOAs and other activities. 

UNDERSTAND HUMAN 

BIOLOGY REDUCE HUMAN DISEASE

DEVELOP WORKFORCE 

AND RESOURCES

ADVANCE TRANSLATIONAL 

RESEARCH
 THE NHLBI STRATEGIC VISION | 51

Initiatives that result from the Strategic Research Priorities will advance 

achievement of the eight Objectives and will have profound impacts on the 

health and well-being of the American public as well as the growing number of 

affected populations around the world. For example, these efforts will enable a 

deeper understanding of biological processes; allow for more precise targeting 

of therapies to patients, leading to approaches and early interventions to prevent 

disease and reduce inequities in health outcomes; and foster a more diversified 

and integrated scientific workforce. 

Success will be realized by ensuring that our priorities remain dynamic and 

responsive to the evolving scientific landscape and emerging opportunities. 

This ongoing iterative Strategic Visioning process will require the continued 

engagement of the varied stakeholders: the scientific community, medical 

professionals, patients and their advocates, professional organizations, 

policymakers, professional groups, and other interested members of the public, as 

well as the NHLBI Advisory Council and staff. Harnessing the creative energy and 

marshaling the sustained participation and commitment of these stakeholders will 

enable achievement of the priorities in the Strategic Vision. 

As the Institute transitions to implementation, we will engage the scientific 

community through think tanks, workshops, and working groups to help us 

further pinpoint specific activities that will advance the priorities in this 

Strategic Vision. 

Success will 

be realized by 

ensuring that 

our priorities 

remain dynamic 

and responsive 

to the evolving 

scientific landscape 

and emerging 

opportunities.
Image credits:

pg 4: Open Heart Surgery, NIH. R. Perry, National Library of Medicine. 1955.

pg 13: Endothelial cells lining blood vessel walls. Christopher V. Carman and 

Roberta Martinelli, Harvard Medical School, Boston, MA “Life Magnified” 

exhibit. 2014. 

pg 15: Confocal Immunofluorescence, mouse lung. Jeffrey A. Whitsett, 

Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. Generated by 

LungMAP Consortium [U01HL122642]. www.lungmap.net. 23 June 2016 

pg 25: Confocal Immunofluorescence, mouse lung. Generated by LungMAP 

Consortium[U01HL122642]. www.lungmap.net. 23 June 2016 Jeffrey A. 

Whitsett, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.

pg 26: Clinical trial patient undergoing an echocardiogram. Albert Einstein 

College of Medicine, New York City, NY. 2016

pg 29: (top right) Beating human cardiac microchamber. Zhen Ma, Jason 

Wang, Peter Loskill, Nathaniel Huebsch, Sangmo Koo, Felicia L. Svedlund, 

Natalie C. Marks, Ethan W. Hua, Costas P. Grigoropoulos, Bruce R. Conklin 

and Kevin E. Healy, Nature Communications. 2015

pg 31 Sickled Cells. National Center for Advancing Translational Sciences 

(NCATS), National Institutes of Health. Accessed July 15, 2016.

pg 39 (upper right) Heart Disease Death Rates by County (2011-2013). 

National Center for Chronic Disease Prevention and Health Promotion, 

Division for Heart Disease and Stroke Prevention. Accessed June 16, 2016

Pg 42: Pathway visualization of genes involved in Heart Disease. Ma X, Gao 

L, Karamanlidis G, Gao P, Lee CF, Garcia-Menendez L, et al. Plos Comput 

Biol. 2015.

pg 43: Gene regulation of gene expression in Sickle Cell Disease patients. 

Quinlan, Idaghdour, Goulet, Gbeha, de Malliard, Bruat, Grenier, Gomez, 

Sanni, Rahimy and Awadalla. Front. Genet 2014

pg 47 (lower center) Researchers at the National Institute of Allergy and 

Infectious Diseases (NIAID), National Institutes of Health. 2012

pg 49 Functionalized silica-encapsulated fluorescent nanodiamonds (FNDs) 

attached to individual DNA molecules are excited by the evanescent field 

(green) in a total internal reflection microscope and emit red fluorescence. 

Susanta K. Sarkar, Neil Billington, Martin W. Brechbiel, and Keir C. Neuman. 

J. AM. Chem Soc. 2013. 

pg 50 A mouse’s fat cells (red) are shown surrounded by a network of blood 

vessels (green). Daniela Malide, National Heart, Lung, and Blood Institute, 

National Institutes of Health. 2015

U.S. Department of Health and Human Services

National Institutes of Health

National Heart, Lung, and Blood Institute

NIH Publication 16-HL-6150