Exploring Inflammation, Cardiometabolic Diseases, and PTSD
by LAURA STEPHENSON CARTER
Nehal Mehta and Jessica Gill recently joined NIH as the first two NIH-Lasker Clinical Research Scholars, a joint initiative of NIH and the Albert and Mary Lasker Foundation that will nurture the next generation of clinician-scientists.
PHOTO BY NICHOLAS ZAGORSKI, NHLBI
NIH's first two Lasker Clinical Research Scholars, Nehal Mehta (left) and Jessica Gill.
Mehta, who has the distinction of being the inaugural NIH-Lasker scholar, came from the Perelman School of Medicine at the University of Pennsylvania (Philadelphia) and now heads NHLBI’s new Inflammation and Cardiometabolic Diseases laboratory. He aims to better understand how inflammation influences insulin resistance, atherosclerosis, and heart disease.
Gill, a Lasker Scholar in NINR, is also studying inflammation, but her focus is on how it affects posttraumatic stress disorder and traumatic brain injury and how the crosstalk between the immune system and the brain can compromise health. She trained at NINR and was most recently at George Mason University (Fairfax, Va.).
The Lasker program selects talented early-stage researchers to do independent clinical and translational research for five to seven years at NIH’s Bethesda campus. After completing their initial tenure, they will have the opportunity to remain at NIH as tenured investigators or join the faculty of an extramural research institution where they can receive up to five more years of NIH financial support (up to $500,000 a year).
The following is a lightly-edited version of interviews with Mehta and Gill.
NEHAL MEHTA, M.D., M.S.C.E.
Lasker Clinical Research Scholar, Section of Inflammation and Cardiometabolic Diseases, Cardiovascular and Pulmonary Branch, NHLBI
Education: Seven-year biomedical program, George Washington University, Washington, D.C. (B.A. and M.D.); University of Pennsylvania, Philadelphia (M.S.C.E. in genetic epidemiology)
Training: Residency in internal medicine and fellowship in cardiovascular medicine, Hospital of the University of Pennsylvania; postdoctoral fellowship in lipoprotein biology and genetic epidemiology, University of Pennsylvania
Before coming to NIH: Adjunct assistant professor at the Perelman School of Medicine, University of Pennsylvania; attending cardiologist and director of Inflammatory Risk, Preventive Cardiology, at the Hospital of the University of Pennsylvania
Outside interests: Spending time with his wife and their three-year-old daughter; cooking; skiing; surfing
How did you become interested in your field?
I have always been interested in understanding “Why?” In particular, I was fascinated by blood-vessel physiology, fluid dynamics, and electromechanical coupling and have wondered about the link between obesity (associated with chronic inflammation) and cardiovascular and cardiometabolic diseases. We did a study in which we induced inflammation in healthy people by giving them a low-dose bacterial endotoxin. We made the striking first-in-human observation that a single dose of endotoxin turned fat tissue dysfunctional and led to insulin resistance (Diabetes 591:172-81, 2010). These studies supported the careful examination of known chronic inflammatory diseases such as psoriasis—which causes skin irritation and inflammation—to understand how varying exposures to inflammation are associated with metabolic and vascular diseases.
What’s the connection between psoriasis and heart disease?
In 2009, I embarked on large epidemiological studies that confirmed the association between psoriasis and heart disease (Eur Heart J 31:1000-6, 2010). Then I helped develop the first national clinic for psoriasis patients to understand their risk for cardiometabolic diseases. Surprisingly, a large percentage of my young patients had high cholesterol, obesity, and pre-diabetes, confirming our prior epidemiological studies. I decided to use psoriasis as a model to better define the interplay of chronic inflammation and cardiometabolic disease. With my nuclear cardiology background, I performed a pilot study using fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) to scan patients for internal inflammation.
What did you find?
Our study was one of the first to show that psoriasis is a whole body disease. The FDG-PET/CT scan revealed that, in psoriasis patients, there’s not only inflammation in the skin, but also in the blood vessels, joints, and liver. This finding was in young patients without risk factors for these diseases, which further supported the fact that inflammation due to T-cells may predispose one to cardiometabolic diseases. (Arch Dermatol 147:1031-1039, 2011)
What’s the research you are doing at NIH?
My proposal for the Lasker was to pose a critical question that everyone asks in the field: “Is inflammation causal in heart disease or is it simply a byproduct of confounding processes?” We are using psoriasis as a model understand how treating inflammation affects pathways associated with metabolic and vascular diseases. Ours will be the first longitudinal study using multiple imaging techniques (PET/CT, PET/MRI and CT angiography) and metabolic diseases markers in multiple tissues (skin, blood, fat) to understand the effect of anti-inflammatory treatments on vascular diseases. We hope to determine whether modulating inflammation matters.
What made you decide to come to NIH?
What better place to continue high-level clinical translational research than the world’s largest and best clinical research center? The environment is collaborative, and enriched in resources, and the amount of support you get as a clinical investigator is unparalleled. I can recruit patients and establish the world’s first laboratory of inflammation and cardiometabolic diseases to study these processes in real time. This opportunity also enabled me to continue a rich collaboration with Penn. and to still see my patients. One of my Penn mentors trained at NIH and spoke incredibly highly of it.
Is there anything you can look back on now and realize it was significant?
In my cardiology fellowship, I was told to focus, focus, focus, but I did not. My avoidance of focusing permitted me to develop skills and link internal medicine, dermatology, radiology, cardiology, and epidemiology. You cannot answer “Why?” without exercising all of these disciplines. Now, however, is the right time for me heed that important advice and focus—on the mechanisms of inflammation.
Would you like to tell us anything else?
To be successful as a translational physician-scientist, you need to marry your clinical work to your research. I love caring for my patients. Each encounter teaches me, stimulates more scientific questions, and also provides tissues to move our understanding forward. My present environment is just perfect for building my clinical program and sustaining high-level science in my lab.
JESSICA GILL, R.N., P.M.H.N.P., PH.D.
Lasker Clinical Research Scholar, NINR
Education: Linfield College, McMinnville, Ore. (B.S. in nursing); Oregon Health and Science University, Portland (M.S. in psychiatric/mental health nursing); Johns Hopkins University School of Nursing and School of Public Health, Baltimore (Ph.D.)
Training: Postdoctoral in NINR/NIMH
Before coming to NIH: Assistant professor, School of Nursing and Krasnow Institute for Advanced Studies at George Mason University (Fairfax, Va.)
Outside interests: Spending time with husband and their three young children; hiking; skiing; camping
How did you get interested in your field?
When I was an undergrad I did an externship at a domestic violence shelter and encountered women who had escaped from their abusive environments but felt sick all the time and weren’t sleeping well. I thought that something was going on with violence and their health. Back then I didn’t know much about posttraumatic stress disorder (PTSD) as it wasn’t a dominant diagnosis.
What was your work before you came to NIH?
I am interested in linking immunology with psychiatric disorders and trying to understand how those mechanisms would impact somebody’s health. My dissertation research reported high rates of PTSD in urban health-care seeking women and that a PTSD diagnosis was associated with perceived health declines, as well as with higher concentrations of inflammatory markers and dysregulation of endocrine functioning. During my postdoctoral fellowship at NIH, I found alterations in the functioning of the immune and endocrine systems in PTSD and depression. Later, as a clinical investigator at NINR and at George Mason, I gained a better understanding of the biological mechanisms of PTSD. (J Am Psychiatr Nurses Assoc 17:404–416, 2011; Trauma Violence Abuse 12:115–126, 2011)
What is your research at NIH?
I’ll be working as part of a Department of Defense-funded collaborative project with NINDS’s Center for Neuroscience in Regenerative Medicine and the Uniformed Services University (Bethesda, Md.) We’ll collect epigenetic biomarkers—such as endocrine proteins that play a role in inflammation—from patients who have been hospitalized for a traumatic event. We’ll examine the biological and neurological factors linked to the risk for PTSD onset and the influence of traumatic brain injuries (TBIs). TBIs can increase the risk for PTSD. We’ll follow patients during their immediate recoveries and for years afterwards to better understand the risk and resiliency factors related to these outcomes.
I will also be working on a study at Walter Reed National Military Medical Center (Bethesda, Md.) to treat insomnia that develops following a TBI. We’re looking at the administration of growth hormone and giving it as a one-time stimulus to see if it would promote sleep in service members who have TBI and insomnia.
What made you decide to return to NIH?
It seemed like a wonderful opportunity especially with the collaboration with the Department of Defense. And I couldn’t turn down the chance to come back to NIH and have more of a leadership role. At NIH, I can expand my research—such as adding advanced imaging to my study—more quickly than if I was somewhere else.
What is most exciting about your work?
Right now if somebody comes into an emergency department we have no way to identify who’s at highest risk for PTSD. Typically the physical injuries will be treated, but we don’t do anything about psychological therapy. So the first step in this is trying to see if we can get a biomarker that predicts who’s going to be more at risk for neurological deficits as well as PTSD.
Is there anything you can look back on now and realize it was significant?
When I was working on my predoc, I wanted to focus on one system—immunology. But a mentor said I needed to take a more comprehensive approach. She encouraged me to look at the endocrine system, too. Now I’m more known for my work in endocrinology than immunology. It’s really the integration between these two systems that’s helped me to understand the work better.
Is there anything else you’d like to tell us?
You have to be passionate about your work. That passion is the only thing that keeps you motivated and focused. Being at NIH gives me the flexibility to do the type of science that I want to do.
To learn more about the Lasker Clinical Research Scholars Program go to http://irp.nih.gov/careers/trans-nih-scientific-recruitments/lasker-clin... or http://www.nih.gov/science/laskerscholar/index.html or contact Charles Dearolf (LaskerScholar@nih.gov or 301-402-1225).