# Success Stories: Franck Kalume

**Franck Kalume, Ph.D.**Associate ProfessorDepartment of Neurological SurgeryUniversity of Washington

**Follow your passion, persevere, and seek the best possible training**

My interest in neuroscience was sparked at an early age, before I was even aware of the existence of this discipline of science and its importance in understanding of the function of the nervous system in health and disease. My first close encounter with a health issue related to neuroscience occurred when I was in my teen years. It was a troubling moment; I was very tormented to see my older sister suffer from episodes of manic depression following her divorce. This event triggered my avid interest in understanding human brain functions and malfunctions. However, I was living in the Democratic Republic of Congo (DRC), my native country, and only had access to a very limited information about the field during that period, so it took several years before I had the opportunity to gain formal exposure and begin exploring this amazing field.

I moved to the US in the mid-1990s to pursue my education, as the DRC was going through tumultuous times marked by civil unrests, wars, and massive deterioration of the country socio-economic status. I first attended LeMoyne-Owen College in Memphis, Tennessee where I obtained my bachelor’s degree in Biology. It was there that I “re-”discovered neuroscience during a summer research program with my great mentor, Dr. Eldridge Johnson. After college, I did my PhD in the Department of Anatomy and Physiology at University of Tennessee under the wonderful mentorship of Dr. Joseph Callaway. I studied the mechanisms responsible for nigral dopamine neuron excitability and generation of distinct modes of firing patterns in slice preparations. In addition, I investigated the pathogenesis of myelopathy/tropical spastic paraparesis associated with human T-lymphotropic virus type-1 (HTLV-1) infection.

For my postdoctoral training, I went to the University of Washington (UW) in the lab of Dr. William Catterall, one of the world leaders in the field of research on the structure and function of ion channels and their roles in normal and disease state. During this time, my mentor suggested that I apply for a diversity supplement to his grant. The experience of putting the supplement together opened my eyes to the process of applying for NIH funding. I learned how important it is to have around you a good team of people who can guide you through the potentially overwhelming volume of instructions, guide you in the art of crafting a compelling application, and help you put all the parts of a grant together. The supplement provided critical funding that allowed me to take my research into a new direction that has been very fruitful and led to where I am now. I conducted a series of exciting studies that led to the discovery that reduced GABAergic inhibition is a key part of the pathophysiological mechanisms of seizures and the diverse comorbidities of Dravet syndrome.

Several years into my postdoc, I began thinking about next steps. It seemed like it would be very difficult to find an independent position, and I wondered if I would have to do another postdoc or if I should change course and go into industry. Luckily, my mentor told me about the NINDS Diversity Faculty K01 award, which I applied to and was awarded just as I ran out of funding. In applying for the NINDS Diversity K01, I was surprised because I thought the application would be all about the science, but a big part of the application is your career development plan. Putting the application together was the first time I sat down and made a formal plan for my career, and it helped me understand everything I had to do to become independent. It also gave me the opportunity to connect with other scientists outside of my lab and have conversations with them about their careers.

Receiving the NINDS Diversity K01 gave me a chance to go into a new research area different than my postdoc lab and let me establish myself. It was crucial in preparing me to become an independent investigator and enabled me to join the faculty of the Department of Neurological Surgery at UW and the Center of Integrative Brain Research (CIBR) at Seattle Children’s Research Institute as an Assistant Professor and Principal Investigator.

As a faculty member, I have participated in the 2012 NINDS grant writing workshop for diverse researchers, as well as the 2014 career advancement symposium organized by the UW based program for Broadening the Representation of Academic Investigators in Neuroscience (BRAINS), an NINDS-funded research education program. These programs provided crucial career development training, such as how to run a lab, interact with other principal investigators, resolve conflict, prepare applications, and manage stress. In 2017, I was awarded my first R01 grant, and NINDS funding has been critical to let me focus all my energy towards preparing the application by providing funding for preliminary data and travel to conferences to network through the K01, combined with enhanced grant writing skills developed from participating in programs like BRAINS.

In the course of my faculty position, I have expanded the scope of my work and established a research program focused on understanding the pathophysiological basis of genetic refractory epilepsies and their co-morbid conditions. My current work focuses on three severe, debilitating, and life-threatening forms of epileptic disorders with distinct genetic etiology: Dravet syndrome, focal cortical dysplasia, and Leigh syndrome. My goal is to pave the way for the development of future drugs and therapeutic approaches for these disorders.

My advice to trainees is to follow their passion, to persevere, to seek the best training possible, and to identify and choose mentors and collaborators who will help them achieve their training and career goals at each step of the way. Building and maintaining a career in science is a long and challenging, these characteristics will help you endure the process. It is important to make time for training in both research and career development.  Also, very important is to get involved and make connections with colleagues in the research field of their interest and related fields. This is an exciting time in science as recent advances in technology and science have opened up amazing new opportunities for research and innovation with potentially great impact on human lives.

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**Current Research**

Work in my lab focuses on understanding the physiological mechanisms that lead to recurrent seizures and related neurological disorders in forms of epilepsy that are difficult to treat and associated with a genetic cause.

My hope is that our findings will lead to breakthroughs in therapeutic approaches for these disorders. My current research projects are centered on three severe, debilitating, and life-threatening epileptic disorders, each caused by a distinct type of genetic abnormality: (1) Dravet Syndrome which is often linked to mutations in *SCN1A*, the gene encoding the *NaV 1.1* channels which are key for the generation and propagation of electrical impulses in neurons; (2) Focal Cortical Dysplasia which has been recently linked to mutations in *PIK3CA*, a gene of the PI3K-mTOR signaling pathway which is critical in normal development and cancer; and (3) Leigh Syndrome, a disease associated with mutations in *NDUFS4*, the gene that encodes portion of the protein complex I which is critical for the ability of mitochondria to produce energy for cells.

My lab uses innovative approaches that combine behavioral assays, patch-clamp electrophysiology, pharmacology, electroencephalography, electrocardiography, electromyography, immunohistochemistry, biochemistry, optogenetic, and virus-mediated gene transfer techniques to uncover changes in neuronal, network, and organ function that lead to these disorders. Based on this insight, my lab designs and tests novel therapeutic approaches for epilepsy and co-existing conditions (i.e, sleep impairment and sudden unexpected death in epilepsy (SUDEP)) in these complex disorders.