Introducing the Newest Laskers
BY LAURA STEPHENSON CARTER, OD, AND JOANNA CROSS, NIMH
Whether they are studying eye diseases, host-pathogen interactions, neurodegenerative diseases, preventing graft-versus-host disease in stem-cell transplants, blood cancers, pediatric sarcomas, or brain tumors known as gliomas, the eight newest Lasker Clinical Research Scholars are hard at work in labs and clinics throughout NIH.
The Lasker Clinical Research Scholars Program is an “intramural–extramural” NIH program in partnership with the Albert and Mary Lasker Foundation. The program funds a small number of exceptional clinical researchers in the early stages of their careers to help them achieve independence. The scholars can work as principal investigators at NIH for five to seven years and then can either remain on the intramural tenure track or move—with three years of funding—to a university or other research institution.
Read on to learn about the newest Laskers, what their research is, the discoveries they’ve made, how they got interested in science, and what excites them about their work.
To learn more about the Lasker Clinical Research Scholars Program and the 15 other scholars who have been profiled in the past, go to https://www.nih.gov/research-training/lasker-clinical-research-scholars.
Lasker Clinical Research Scholar, Division of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute
EDUCATION: Princeton University, Princeton, New Jersey (Bachelor of Science and Engineering); Washington University, St. Louis, Missouri (M.D.–Ph.D.)
TRAINING: Intern, Transitional Year Program, Presbyterian Hospital (Philadelphia); residency in ophthalmology, Scheie Eye Institute, University of Pennsylvania (Philadelphia); Medical Retina Clinical Fellow, NEI
CAME TO NIH: In 2007 for training; became a staff retina clinician in 2009; named Lasker Clinical Research Scholar in 2018
Research focus: Clinical research in retinal degenerative diseases. The retina is uniquely positioned for advancement in therapeutic intervention for disease. Its accessibility and biology—as well as advances in functional-assessment tools and imaging—make the subject poised for progress in advancing translational research. I use multidisciplinary approaches to understand the patterns of photoreceptor dysfunction and degeneration in disease and to design and implement interventional clinical trials.
Have you made any significant discoveries? Our study (NCT01352975) investigating the findings of dark-adaptation abnormalities in age-related macular degeneration (AMD) has led to significant contributions in understanding disease pathophysiology. Both cross-sectional and longitudinal analyses have revealed functional information about earlier stages of AMD, lend biologic insight into the disease, and have the potential to be used as outcome measures in clinical trials. (Ophthalmology 122:2053–2062, 2015; Ophthalmology 124:1332–1339, 2017; and Ophthalmology DOI:10.1016/j.ophtha.2018.09.039)
Our study of patients with hydroxychloroquine-induced retinal toxicity has led to important findings in understanding the sequence of events in induced retinal degeneration. The drug is used to treat malaria as well as rheumatoid arthritis, lupus, and other autoimmune diseases. Prospective clinical study has helped clarify which tests are most important in revealing pathologic changes in the retina and has public-health impact in helping to inform screening. (Invest Ophthalmol Vis Sci 59:1953–1963, 2018, and Ophthalmology 122:356–366, 2015)
How did you get interested in science and your field? I have always been interested in math and science and in understanding how things work. In college I melded these interests by majoring in chemical engineering. I later realized that questions of human disease were of most interest to me, and I shifted my research interest to a translational focus. Ultimately, the field of ophthalmology sparked my interest, and I was immediately drawn to the study of retinal disease.
What do you find exciting about your work? I am excited and fortunate that my work furthers progress on treating and preventing blindness. Interventional studies and natural history studies both pave the way for the developments of new treatments in areas that are currently lacking successful approaches.
What’s hot in your field right now? New studies to develop treatments where none currently exist, especially in diseases such as atrophic (dry) AMD in which treatment is a public-health need.
What do you like to do outside of work? I love spending time with my husband, three kids, and puppy. The NIH is like family and I am lucky to be able to be part of an environment that fulfills me and enriches me as a person.
If I had more time I would…be less late to everything. I love having a full work life and personal life, but I am always wishing for more hours in the day.
What about you would surprise most people? I have a great group of neighborhood friends who meet up in the predawn hours to run. Combining chatting and exercise is a great way to start the day.
Lasker Clinical Research Scholar, Chief, Bacterial Pathogenesis and Antimicrobial Resistance Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases; Director, Genomics Section, Microbiology Service, Department of Laboratory Medicine, NIH Clinical Center
EDUCATION: Wesleyan University, Middletown, Connecticut (B.A., M.A.); Harvard University, Boston (Ph.D.); and Harvard Medical School, Boston (M.D.)
TRAINING: Resident in Pathology and Edgar Taft Fellow in Medical Microbiology, Massachusetts General Hospital, Boston
CAME TO NIH: In 2013 as staff physician and co-director of the Bacteriology, Parasitology, and Molecular Epidemiology Sections of the Microbiology Service in the Department of Laboratory Medicine, NIH Clinical Center
Research focus: The evolution of bacterial pathogens, host-pathogen interactions, and mechanisms of antibiotic resistance in these organisms. My lab uses a variety of computational biology approaches, including genomic sequencing, transcriptional profiling, proteomic studies with mass spectrometry, and in vitro adaptive-evolution experiments.
Tell us about some of your recent research. We have recently begun to study the utility of nanopore sequencing for the diagnostic identification of antibiotic-resistance genes in bacteria. Using this method, which offers an extremely rapid approach to genomic sequencing, it is possible to identify all of the antibiotic-resistance genes in bacteria isolated from a patient in a matter of hours. Other work focuses on in vitro models of adaptive evolution to understand how bacterial antibiotic resistance emerges and evolves during the course of treatment in patients. We have recently begun to study how some bacteria can increase their mutation rates by turning off DNA-repair mechanisms, thus possibly facilitating more rapid adaptive evolutionary escape from attacks by the host immune system and antibiotic treatment.
How did you get interested in science and your field? I grew up in a house that always had the latest issue of the New England Journal of Medicine, which both of my parents read, open on the kitchen table, and I was exposed to the concepts of medical research from an early age. As an undergraduate, I was introduced to the field of biophysics, which connects math, physics, chemistry, and biology; this introduction has since driven my main interests and approach to biological research problems. In medical school, I became interested in infectious diseases and the biology and evolution of microorganisms, and I came to appreciate the profound importance of the problems caused by the evolution of antibiotic resistance in bacteria. The field of medical microbiology allows me to connect basic biological questions relating to bacterial evolution with fundamentally important clinical aspects of antibiotic resistance and infectious disease.
What do you find exciting about your work? Studying fundamental biological and evolutionary processes in microorganisms and the interactions of these processes with the human immune system. It is a privilege to get to work daily on these important problems with so many smart, creative, and dedicated colleagues at the NIH.
What’s hot in your field right now? The availability of rapid and easy whole-genome sequencing of microorganisms has opened up a variety of research and diagnostic possibilities in the field of medical microbiology. For instance, bacteria from infections in patients that display unusual patterns of antibiotic resistance can be rapidly sequenced, revealing information about the molecular mechanisms underlying resistance.
What do you like to do outside of work? Read; visit museums; eat; and spend time with my wife and our horse (Bailey).
What about you would surprise most people? I’m a bit of a science fiction nerd. But that probably wouldn’t surprise anyone.
Lasker Clinical Research Scholar, Center for Cancer Research, National Cancer Institute
INTERVIEWED BY JOANNA CROSS, NIMH
EDUCATION: Harvard College, Cambridge, Massachusetts (A.B. in history and science); Duke University School of Medicine, Durham, North Carolina (M.D.)
TRAINING: Residency in internal medicine, fellowship in medical oncology, fellowship in hematology; all at Johns Hopkins University School of Medicine (Baltimore)
CAME TO NIH: In 2014 as an assistant clinical investigator in NCI-CCR’s Experimental Transplantation and Immunology Branch; in 2018 became a Lasker Clinical Research Scholar/Tenure-Track Investigator
Research focus: Translational laboratory and clinical research related to allogeneic hematopoietic-cell transplantation. In particular, I am working toward developing and better understanding the use of post-transplantation cyclophosphamide (medication used to modulate the immune system) to prevent graft-versus-host disease (GVHD). My goal is to improve transplantation outcomes for patients. This improvement includes further reducing the incidence and severity of GVHD and infectious complications, improving immune reconstitution, and better preventing and treating malignancy relapse post-transplant.
What would you say is your most significant discovery? My most significant discovery to date, and probably the thing of which I am most proud, has just been accepted for publication. It has to do with understanding how post-transplantation cyclophosphamide prevents GVHD, which can be a major complication of allogeneic hematopoietic-cell transplantation. In the past few years, the therapeutic use of post-transplantation cyclophosphamide has been increasing worldwide; it is being used as a standard of care by many institutions because it allows half-matched transplants to be performed safely and also is unique in preventing chronic GVHD without having to remove the T cells from the graft. Yet the mechanisms of action of post-transplantation cyclophosphamide are still not well understood. Investigators worldwide believe that cyclophosphamide prevents GVHD by selectively eliminating alloreactive T cells. However, my research in mice shows that post-transplantation cyclophosphamide, in fact, does not eliminate alloreactive T cells. Furthermore, intrathymic deletion of alloreactive T cells also is not necessary for the therapeutic efficacy of post-transplantation cyclophosphamide, as is also believed. By contrast, we found that alloreactive T cells persist despite post-transplantation cyclophosphamide, but they become functionally impaired. This effect is aided by the rapid, preferential recovery of regulatory T cells, which we have previously shown. In the new study, we provide additional insight into their role. These findings should prompt a paradigm shift in our understanding of how post-transplantation cyclophosphamide works and facilitate the development of new strategies to improve transplantation outcomes that are based on biology and not a on flawed understanding.
How did you get interested in science and your field? I have been interested in science and medicine since high school. In medical school, I spent a year at NIH as part of the Howard Hughes Medical Institute–NIH Research Scholars program and worked in Daniel Weinberger’s lab (National Institute of Mental Health), where I used a B-lymphoblast cell model to contribute to research on cell migration and adhesion. This work subsequently led to my fascination with immunology. During my residency in internal medicine at Johns Hopkins, I explored what clinical field would best integrate with my interest in immunology. I found that hematology, particularly as it relates to leukemia and hematopoietic cell transplantation, best fit with my clinical and scientific interests.
What do you enjoy about your your work? As a physician–scientist, I enjoy developing new understandings in the lab that can be taken directly to the clinic; and also taking clinical observations to the lab, where I can learn about the biology. My goal is to use this improved scientific understanding to improve patient outcomes. I also find great enjoyment in teaching and mentoring trainees at all levels both in the lab and in the clinic.
What is hot in your field right now? Post-transplantation cyclophosphamide. It has had a dramatic impact on the field over the past several years because it provides donors for nearly all patients who need them and helps prevent chronic GVHD. The therapy is cheap and easy to administer. We also are fortunate to have many new tools, including novel cellular therapies such as chimeric antigen receptor T (CAR-T) cells.
What do you like to do outside of work? I have two young children, and they take up most of my time outside of work. Outside of work and family, I sing with the City Choir of Washington, swim, and teach Sunday School to fourth graders at my church.
If I had more time, I would…sleep! In all seriousness, I would love to be able to catch up with my work so I could spend more time with my kids. Also it would be wonderful to have more time to read, both for work and for pleasure.
What about you would surprise most people? That I am not as serious as I appear at work. Due to my hectic schedule and type of job, I have to be very businesslike and professional at work, but my joking side is a prominent feature of my personality outside of work!
Lasker Clinical Research Scholar and Chief, Translational Allergic Immunopathology Unit, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases
EDUCATION: Pomona College, Claremont, California (B.A. in chemistry); Jesus College, Cambridge University, Cambridge, England (two terms as a humanities student); Keck School of Medicine, University of Southern California, Los Angeles (M.D.)
TRAINING: Residency in internal medicine (later served as chief resident) at the University of California at San Diego (San Diego); clinical fellow in allergy and immunology, NIAID
CAME TO NIH: In 2011, for NIAID clinical fellowship in allergy/immunology; in 2014, became an assistant clinical investigator in NIAID’s Genetics and Pathogenesis of Allergy Section; in 2018, named a Lasker Clinical Research Scholar and chief of the Translational Allergic Immunopathology Unit
Research focus: Using human immunogenetics to identify how alterations in signaling, protein expression, and metabolism can affect anaphylaxis and myeloproliferative disease. I am trying to gain a better understanding of the immunopathogenesis of allergic reactions as well as explore novel interventional approaches for the treatment and prevention of severe allergic reactivity and anaphylaxis in people.
Have you made any significant discoveries? The study of human diseases at NIH frequently focuses on rare diseases. Since joining NIAID, I have been integrally involved in the discovery of many single-gene disorders that lead to severe allergic diseases or reactions, and there are several more in the pipeline (J Exp Med 215:1009–1022, 2018). However, one of these discoveries, which is critical to my program going forward, was the identification of a genetic trait we have called hereditary alpha-tryptasemia. Caused by an increased copy number of the TPSAB1 gene, this trait affects approximately five percent of the Caucasian population and is associated with severe allergic reactions as well as several other difficult-to-treat symptoms. (Nat Genet 48:1564–1569, 2016)
How did you get interested in science and your field? As far back as I can remember, I have wanted to understand how things worked and find a deeper meaning underlying it all. I remember being a grade schooler and learning for the first time that if you looked closely enough, solid things are really not “solid” at all in the classical sense, and I was hooked. My desire to find that deeper meaning ultimately directed me toward a career as a physician. Ultimately, my fascination with the complexity of immunologic responses and the diseases and reactions they cause, and a desire to better understand these processes to inform therapies, is why I chose the field of allergy and immunology.
What do you find exciting about your work? We sit at a unique time in medical history when we can see a patient in clinic, solve the genetic or immunologic riddle that underlies their severe medical problem, identify a pathway that we can target, and provide a medicine that can treat the disease and improve the patient’s quality of life. We aren’t always successful, but changing even one life this way has been the honor of my lifetime.
What’s hot in your field right now? As with many fields currently, precision medicine is really at the forefront of clinical immunology research. This precision-medicine approach is precisely what my lab hopes to facilitate through the translational work we are undertaking.
What do you like to do outside of work? Cook and spend time with my family. I do all the meal planning and cooking, and my three-year-old son helps with the grocery shopping early every Saturday morning.
If I had more time I would … ah—so many things! A major thing would be to travel back to the West Coast to see my family and spend time with my kids in the places I loved growing up—outdoors in the mountains and ocean.
What about you would surprise most people? That probably depends a lot on who you ask. Childhood friends are often surprised that I am a “hardcore” scientist with a lab. Professional colleagues would likely be surprised to hear that I played football in college and that I am a huge underground hip-hop fan.
Lasker Clinical Research Scholar and Chief, Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke
EDUCATION: Medical University of Innsbruck, Innsbruck, Austria (M.D.); University College London, Queen Square Institute of Neurology, London, United Kingdom (Ph.D. in neurogenetics)
TRAINING: Postdoctoral fellowship in neurogenetics, National Institute of Aging; postdoctoral fellowship in neuroscience, Georgetown University (Washington, D.C.); internship and adult neurology residency, Johns Hopkins University Medical Center (Baltimore)
CAME TO NIH: In 2005 for training (2005–2009); returned in 2015 as assistant clinical investigator in NINDS; became Lasker Clinical Research Scholar in 2018
Research focus: My research program takes full advantage of the rapid advancements in genomic technologies together with marked progress in computational capabilities that provide unprecedented opportunities for gaining insights into the molecular defects underlying neurologic diseases. In my lab, we are unraveling the genetic causes of complex neurodegenerative diseases, including Lewy body dementia, multiple-system atrophy, and related Parkinsonism syndromes. We aim to use genetic information not just for advancing our understanding of these conditions but also to improve diagnostic accuracy and targeted treatments by incorporating genetic knowledge into routine clinical assessments.
Have you made any significant discoveries? My genomic research has had a significant impact on our understanding of genetic risk involved in neurodegenerative diseases, including the discovery of genes underlying Parkinson disease, Lewy body dementia, ataxia, and rare parkinsonism disorders. For example, I have shown that Lewy body dementia shares numerous molecular risk factors with Parkinson disease and Alzheimer disease (Neurobiol Dis 94:55–62, 2016). These insights have resulted in a multicenter, international effort to perform genome-sequencing of large cohorts with this underserved dementia syndrome and to extend modern gene discovery efforts to this disease.
As a neurologist-scientist, I am acutely aware that establishing an accurate clinical diagnosis in complex neurodegenerative syndromes remains challenging due to clinical overlap among patient groups and unspecific early symptoms of disease. I was part of an international team that developed the NeuroChip genotyping platform, a high-throughput genotyping array that allows us to rapidly screen individuals for known disease-associated genetic variants (Neurobiol Aging 57:247.e9-247, 2017). We have already genotyped diverse autopsy-confirmed neurodegenerative disease cases using this versatile platform and identified instructive genotype-phenotype correlations (Neurobiol Aging 2018; DOI:10.1016/j.neurobiolaging.2018.11.007).
We are now applying machine-learning techniques to genomic data to identify genetic patterns that allow us to distinguish these complex diseases. Ultimately, these efforts might result in the development of novel ancillary diagnostic tools.
How did you get interested in science and your field? Ever since secondary school, I have enjoyed reading popular science magazines and science-fiction novels. During high school I worked as a volunteer paramedic, which was a major impetus for my decision to become a physician. Later in medical school, I became fascinated by the brain. I remember sitting in lectures and being enthralled by the marvelous tales of how the brain works, and I was hooked on making neurology and neuroscience research my career.
What do you find exciting about your work? The knowledge that understanding the molecular mechanisms of a disease paves the way for treatments in the near future. As a neurologist who continues to see patients afflicted with these diseases in the clinic, this knowledge is the most important dimension of what I do and what gets me up in the morning.
What’s hot in your field right now? The major development in neurogenomics is that large-scale genome-sequencing efforts have become a reality. As a field, we have to find out how to best integrate different layers of -omics data using modern computational applications such as artificial intelligence. The human brain excels at picking out patterns in two and three dimensions, but it has difficulty beyond four dimensions. This is where machine learning excels. The irony that I use artificial intelligence to study real intelligence is not lost on me.
What do you like to do outside of work? Between my clinical work and my research, I don’t have much time. What little I do have, I like to relax with a good book surrounded by my two cats, Bill and Hillary.
If I had more time I would…I know that this sound really nerdy, but I’d study more. Computer science and astrophysics are two topics I would love to delve further into.
What about you would surprise most people? I have a glider pilot’s license.
Lasker Clinical Research Scholar, Head, Unit on Clinical Translational Immunology, Laboratory of Immunology, National Eye Institute
EDUCATION: Hacettepe University Medical School, Ankara, Turkey (M.D.); Duke University, Durham, North Carolina (M.H.S.)
TRAINING: Residency in ophthalmology, Ankara Training and Research Hospital (Ankara, Turkey); clinical fellowship in uveitis and ocular immunology, NEI; residency in ophthalmology, George Washington University (Washington, D.C.)
CAME TO NIH: In 2001 for training; returned in 2008 as a staff clinician; became Lasker Clinical Research Scholar in 2018
Research focus: Developing outcomes measures, biomarkers, and targeted therapies for the treatment of uveitis, an immune-mediated eye disease, and improving our understanding of the pathways driving it. Uveitis is a multifactorial disease whose etiology remains elusive and whose treatment continues to be a challenge despite recent advances.
Tell us more about your current research. I lead two major studies: one that investigates molecular profiling of clinical phenotypes of uveitis and another that investigates the role of gut microbiome in uveitis patients from both a mechanistic and biomarker perspective. Both involve intramural and extramural collaborations with basic and clinical scientists and has the potential to yield new ways of altering the course of the disease and lead to targeted therapies.
Have you made any significant discoveries? During my fellowship at NEI, I developed a standardized grading system for scleritis (inflammation of the white part of the eye) using NEI’s electronic ocular-image database (Ophthalmology 1118:768–771, 2011; DOI:10.1016/j.ophtha.2010.08.027). The grading system is now used in clinical studies and has been adopted by an open-source electronic medical-record system in the United Kingdom. I have established diagnostic criteria for autoimmune retinopathy, a rare disease, and described aberrant immune phenotype in patients who have it (J Neuroimmunol 316:74–79, 2018; DOI:10.1016/j.jneuroim.2017.12.014). I was also one of the first to investigate the possible association between the gut microbiota and uveitis in humans (Invest Ophthalmol Vis Sci 58:846, 2017, ARVO annual meeting abstract).
How did you get interested in your field? In medical school, I volunteered (every summer) in a cancer immunology lab in Turkey. That work led to my visiting an immunology lab in the United States, which expanded my vision for science. Later, during my ophthalmology residency, I became interested in uveitis, which is responsible for up to 15 percent of all cases of total blindness in developed countries and affects people in their most productive years. This interest led me to choose clinical fellowship training in uveitis and ocular immunology in the United States, specifically at NEI. During this time I realized that I was most passionate about clinical research that can be translated to patient care and that could affect patient outcomes.
What do you find exciting about your work? The opportunity to combine clinical research with translational research. I feel fortunate to be able to perform clinical studies and trials with a mechanistic component and collaborate with the best in the field. It is the perfect example of bench to bedside, though in my case its more of a “bed to bench to bedside.”
What’s hot in your field right now? The microbiome and its interaction with the immune system and the eye; and novel imaging approaches.
What do you like to do outside of work? Spend time with my family; swim; practice yoga; cook
If I had more time I would … spend more time with my family and travel for leisure.
Lasker Clinical Research Scholar, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute
EDUCATION: University of Notre Dame, South Bend, Indiana (B.A. in preprofessional studies); The Medical College of Georgia, Augusta, Georgia (M.D.)
TRAINING: Residency in pediatrics, University of Chicago Comer Children’s Hospital (Chicago); combined fellowship in the pediatric hematology and oncology training program, Johns Hopkins University (Baltimore) and National Cancer Institute
CAME TO NIH: In 2010 for training; became assistant clinical investigator in 2015; became Lasker Clinical Research Scholar in 2018
Research focus: Defining the biology, genetics, and epigenetics of pediatric sarcomas with the goal of developing novel therapies; developing sequencing assays that can be incorporated into diagnostic and prognostic clinical care; resolving tumor heterogeneity and genetic mechanisms of tumor resistance; and therapeutic targeting of epigenetic vulnerabilities in pediatric sarcomas, namely rhabdomyosarcoma and malignant peripheral nerve–sheath tumors.
Have you made any significant discoveries? I was lucky enough to join the laboratory of Javed Khan as a clinical fellow. At that time, next-generation high-throughput sequencing was first being applied to patient samples in an effort to identify the genetic changes that drive tumorigenesis. I led a project that collected patient tumor samples from a disease called rhabdomyosarcoma and applied sequencing technology. We were able to describe the “landscape” of mutations that define this disease, and we gave the research community a list of targets to develop therapies toward (Cancer Discov 4:216–231, 2014).
How did you get interested in science and your field? I have always been interested in understanding how things work. Some of my early classes in chemistry and biochemistry opened my eyes to the complexity of natural systems. I come from a family of architects and engineers, and in many ways what we do in science and medicine is similar to those professions in that we first study the problem and then try to build solutions.
What do you find exciting about your work? I love the discovery and inventiveness that goes with working in the laboratory. It is exciting to put together diverse teams of brilliant people and challenge them with an unsolved problem. There is nothing quite as fun as being part of a team that really starts to click. As a physician, the most exciting part of the work is the opportunity to take discoveries from the laboratory and use them to help patients in the clinic.
What’s hot in your field right now? Immunotherapy and specifically chimeric antigen receptor cells are revolutionizing how we treat pediatric cancer patients. In the genomics field, the development of methods to do single-cell sequencing are allowing us to do experiments at a whole new level of resolution and understand complex problems such as tumor heterogeneity and resistance to therapy.
What do you like to do outside of work? I love spending time with my wife, four-year-old daughter, and friends. I love to garden, bike, and travel.
If I had more time I would … get better at coding.
What about you would surprise most people? I have no surprises. I am an open book.
Would you like to tell us anything else? To the trainees, I would say be persistent and take chances. The NIH is such a great place to train and to get involved with big projects that will change fundamental understandings and the way we do medicine.
Lasker Clinical Research Scholar, Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute
EDUCATION: Capital Medical University, Beijing, China (M.D.); University of Texas Medical Branch, Galveston, Texas (Ph.D. in neuroscience)
TRAINING: Postdoctoral fellow, Department of Anatomy and Neuroscience, University of Texas Medical Branch (Galveston, Texas); residency in neurology (including chief resident), University of Texas Health Science Center (Houston); and a clinical neuro-oncology fellowship, University of Texas MD Anderson Cancer Center (Houston)
BEFORE COMING TO NIH: Co-director, Brain Tumor Program, Lineberger Comprehensive Cancer Center, and tenure-track assistant professor, Department of Neurosurgery and Neurology, University of North Carolina Medical School (Chapel Hill, North Carolina)
CAME TO NIH: In 2015 as staff physician; became Lasker Clinical Research Scholar in 2018
Research focus: Identifying clinically relevant challenges in patients with primary brain tumors; developing hypothesis-driven laboratory projects in preclinical models; and ultimately translating results into clinical trials to determine predictors and mechanisms of treatment responses or resistance.
Tell us more about your research. In particular, I focus on gliomas with mutations in the IDH gene, which is linked to longer survival regardless of the cancer’s stage at diagnosis. I have also developed clinical trials to test combined therapies in recurrent glioblastomas, which are more aggressive than IDH-mutant gliomas.
Have you made any significant discoveries? During my clinical neuro-oncology practice at UNC, I observed that patients with IDH-mutant gliomas respond to chemotherapies better than those with wild-type (WT) gliomas. I took this observation and started an investigation in my laboratory to test the hypothesis that IDH-mutant gliomas are more sensitive to chemotherapies than IDH WT gliomas. I later discovered that IDH mutations make gliomas even more sensitive to chemotherapy. In collaboration with colleagues at both UNC and NCI-CCR, we discovered two proteins, ALKBH (now ALKBH1, alkylation repair homolog 1) and PARP [poly(ADP-ribose)-polymerase], that repair the DNA damage induced by chemotherapies. These findings not only elucidated the mechanisms of chemosensitivity but also provided the basis for developing therapeutic approaches to target the specific vulnerability of this subset of gliomas with IDH mutation. (Cancer Res 77:1709–1718, 2017; and Cell Rep 13:2353–2361, 2015). Based on my preclinical findings in my glioblastoma research, I designed and opened the first clinical trial (NCT02942264) with TG02 in recurrent glioblastoma Clin Cancer Res, 2018; DOI:10.1158/1078-0432.CCR-17-2032). TG02 is an agent with known penetration of the blood-brain barrier and had been used previously in trials of hematological malignancy.
How did you get interested in science and your field? I have always liked neuroscience because it is complex yet very logical. My Ph.D. mentor, William D. Willis (University of Texas Medical Branch), had a great influence on me. He was a giant in the field of neuroscience and in particular the field of pain research. Proud to be one of his 22 graduate students, I studied pathways that carry pain impulses from the spinal cord to the brain and elucidated the mechanisms underlying chronic pain. More importantly, I enjoyed studying neuroscience and learned from him how to approach research questions. Knowing that I was interested in neurological diseases, he supported my decision to pursue a neurology residency. In his later years, he always encouraged me not to give up research despite my busy clinical training and practice.
I had never planned to study neuro-oncology until my clinical rotation at University of Texas MD Anderson Cancer Center, which was one of the two cancer centers in the country that had a department of neuro-oncology. The dismal prognosis and the lack of treatment of brain cancers made them a death sentence. I was shocked at how little we knew about the brain tumors. The fellowship director, Vinay Puduvalli, talked with me about a seminal publication, the results of which established the standard-of-care for newly diagnosed glioblastoma (New Engl J Med 352:987–996, 2005) [https://www.ncbi.nlm.nih.gov/pubmed/15758009]. I was amazed by the impact of this research to save patient lives. He took me to his laboratory, where I did my first cell culture of glioma stem-like cells. I later met Mark Gilbert, a professor in the Neuro-oncology Department, from whom I learned the power of clinical-trial research in neuro-oncology. I felt that neuro-oncology was the field in which my passions for both clinical practice and research could merge the best. I guess this belief is the major reason why I chose to study brain tumors.
What do you find exciting about your work? Having the privilege of taking care of my patients in both a clinical setting and using clinical challenges to further translational research in the laboratory. Clinical practice not only fulfills my desire to be a good physician but also provides me with so many research questions. The hypotheses that are built on clinical observations are never hypothetical but represent a real problem and a true barrier to making progress in the field of neuro-oncology. The enriching research environment of NCI and NIH allows physicians to practice true academic medicine. The resources and collaborative support that I have received as a clinical investigator at NIH has been unparalleled. I can perform preclinical investigation in the laboratory and design clinical trials based on the findings in the lab. I can recruit patients to clinical trials, which will allow for clinical investigation and advanced hypothesis-driven correlative studies in the laboratory. I don’t believe this type of work can be done anywhere else. I am fortunate to be at the right place and right time for the translational research that will benefit brain-tumor patients.
What’s hot in your field right now? As in many other fields, immune therapy is a hot topic in neuro-oncology.
What do you like to do outside of work? I don’t have much time outside of work. But when I do, I like to read for leisure or spend time with my family and my cats.
If I had more time I would … sign up for a ballroom dancing class or take some piano lessons.
What about you would surprise most people? I have more photos of my cats than anything else on my phone.
Would you like to tell us anything else? I am forever thankful for those who helped me when I needed it the most. One of those was my Ph.D. mentor, William Willis, who offered kindness, trust, unconditional support, and opportunities to me when I first came to United States. Without him, I could not have become who I am, or have gotten to where I am today.
I have always felt so privileged to have the opportunity to take care of my patients during the difficult times of their lives. I am a physician at heart, and I am just trying to exercise all disciplines and use what I have learned to answer the question, “Why does this disease or phenomenon occur and why does it occur in this patient but not others?” Clinical practice is the source of ideas for my bench research and what my research projects are built upon. It is most rewarding to know that my research may bring hope to patients and help relieve their suffering. It is the trust and encouragement from these patients that motivate me to keep going in the field of neuro-oncology.