Dr. Nehal Mehta — Psoriasis, Inflammation, and Cardiovascular Risk

Tuesday, January 22, 2019

Dr. Nehal Mehta currently directs the largest ongoing cohort study to date in psoriasis, which is an inflammatory skin disease associated with increased cardiovascular risk. His research is showing that local inflammation in different areas of the body such as the teeth, scalp, knees, skin, or gut has systemic consequences. And treating that local inflammation can help heal heart disease.

Nehal Mehta, M.D., M.S.C.E., F.A.H.A., is the inaugural NIH Lasker Clinical Research Scholar and a Principal Investigator in the Section of Inflammation and Cardiometabolic Diseases at the NIH's National Heart, Lung, and Blood Institute (NHLBI). Learn more about Dr. Mehta and his research at https://irp.nih.gov/pi/nehal-mehta.

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Transcript

>> Today on Speaking of Science:
>> Remote areas of inflammation in the body -- in your teeth, in your scalp, in your knees, on your skin, even in your gut -- I wanted to show that that local inflammation has systemic consequences.
>> Hello and welcome to Speaking of Science. I'm your host, Ben Chambers of the Intramural Research Program at the National Institutes of Health, also known as the NIH IRP. And today I'm speaking with Dr. Nehal Mehta, who currently directs the largest ongoing cohort study to date in psoriasis, which is an inflammatory skin disease associated with increased cardiovascular risk. His research is showing that local inflammation in different areas of the body such as the teeth, scalp, knees, skin, or gut has systemic consequences. And treating that local inflammation can help heal heart disease. We had a great discussion, so please enjoy my conversation with Dr. Nehal Mehta.
>> I have heard that you enjoy surfing; do you have a favorite surf spot that you've come across in your travels?
>> I have. So I love surfing in Costa Rica. And it's interesting to start an interview on science not on science. So I appreciate that. I grew up on the southern coast of New Jersey on a small island, and I was on the surf team there. So starting around 13 I had been surfing for pretty much every day after school winter, spring, summer, fall.
>> Wow.
>> And to this day I take one trip a year where I will try to still either get in the water. I'm teaching my nine-year-old how to body board and body surf. And I still do get in whenever I can.
>> Whoa. So that was a high school surfing team?
>> It was a high school surfing team in South Jersey. There was at least five or six high schools -- Cape May, Manalapan -- that had surf teams. And I would actually go and surf. It was a formal sport. We would drive to different venues. And we would drive up and down. And who would have thought that New Jersey has surf? But it's actually pretty good -- four- to six-foot waves.
>> Wow.
>> And so we're actually going to June to Costa Rica. And that's a place where I'll surf on the west coast of the island.
>> Ah. Yeah, I've surfed the west coast. Well, I've surfed in one place on the west coast side, Playa Hermosa near Santa Teresa?
>> Oh, yeah. Yeah, yeah. Did you like it?
>> Yeah, that was -- that's actually the beach I always say is my favorite beach. I just thought that was such a cool beach.
>> Yeah, totally. And the wave formations there when the tide goes out are great, actually.
>> Yeah. Well, I wish I was better, I'd go surfing with you sometime.
>> Well, I mean, you know, what I've been telling my daughter is that the first you got to love is just the wave, the ocean, right? You just got to look and really understand that that is really interesting that we can figure out how to ride it. And then I long board now. I don't short board anybody just because it's a little bit harder on the body to short board. But, you know, someday I'll show you some of my best surf spots. I mean, they're right in New Jersey. So if you ever get a chance, Manalapan, New Jersey is a great surf spot.
>> Oh, okay. Cool. Especially in January, right?
>> Yeah, in January. Manasquan in January is awesome. You just make sure you have a dry suit.
>> Uh-huh, yeah [Laughs]. Cool. So did you -- was there anything you learned in your experience in surfing that might have helped you had in your research at the NIH?
>> That's a really good question. I think that the biggest thing that I learned in being a surfer on the surf team is resilience and determination. I mean, it is really hard if you get caught in the wrong part of the wave or the impact zone and you need to keep getting out, you just got to make sure you don't panic and you go back to your basics and you go to your foundation. So when I have complex questions of science, I always say, "Keep it simple, what's your questions, and let's make sure we go back to the basics." So I think that alone -- and that I don't think came just from surfing. It was just general athletics and -- and in my life I've always felt that, you know, discipline and hard work are part and parcel to being a good athlete. And I also believe that in the lab as well.
>> Yeah, I'm sure there's a lot of tough times in the lab with the research that just doesn't work out or a paper gets rejected and you've got trainees and post-docs.
>> Yeah. And I also think it taught me how to have thick skin. There's a side of me that would drive -- so funny story. The reason that at 13 I got my first job as a busboy so that my mom would have to drive me to the beach. Because the restaurant was on the beach. So that was my way of getting to the beach was I would tell her that. But what it also taught my was that sometimes you try your hardest to get somewhere and you think that everything is lined up perfectly, and you there and it's flat. There's no waves.
>> Yeah.
>> Right? So you could be super disappointed, right? Or you could make the best of it. You're like, "Here, I'm at the beach at 6:00 in the morning. I'm just going to chill and I'm not going to surf," right? So I've learned that in the lab as well, that if something you were really thinking is going to work out doesn't, it's okay.
>> Yeah.
>> It's okay, right? Life's going to go on. There's another day tomorrow, exactly.
>> Yeah. My favorite time on the beach is 6:00 in the morning with calm water. But once I get to be a good surfer --^*
>> I actually love -- I love anytime. Anytime I can be on the beach. And so we make it a point -- my family and I and my wife, we make it a point to take at least one trip to the beach a year, and that is the surf trip. But in any other way, if we could sit anywhere near water -- it doesn't have to be a beach, it could be a river or stream -- we try to do it.
>> Cool. In your adventurous life, how did you find your way into science?
>> So in 11th grade there was something in New Jersey called The Governor's School for the Environmental Sciences. And what it is, is you can apply as a student in anywhere New Jersey. And there was one on the sciences, there's one on environmental sciences. And I got very interested being at the beach. And I was also a Boy Scout. So I used to do a lot of dune grass plantings on the beach to protect our ocean. I started realizing that there is something humanly possible when nature is sort of, you know, overturning what we would expect it to not overturn. So in 11th grade I went and joined the Governor's School on the Environment. I spent three weeks checking salinity of water, checking, like, where condor nests are, like, very interesting things about the environment. And South Jersey, unbeknownst to many because of all of the negative publicity it had gotten about its, you know, dirty beaches, is a very beautiful area. And Brigantine National Wild Reserve actually got me interested in science. I would go there and I would check, like I said, the saline of the water. We used to seine across the river and see what we would find. And that got very interesting to me. And I said this is neat. There's almost a one-to-one relationship with the saltwater content and what is in that water. So that, then, made me start asking questions. And my father, a physician, was also a biochemist -- is also a biochemist. And he practices GI, he practices gastroenterology. But he had always instilled in me one very important quality, which was ask a question and then seek for that answer. Don't ask a question and go somewhere -- just really try to stay focused on one thing. And that got me interested, was that I looked at wow, Jersey's beaches and waters and wildlife are directly proportional to the salt content of the water, what's in the precipitation, what's in the air. And then after that, it was a series of just, you know, sort of being interested in math and science and finding that I have a lot of ability to answer questions if they're asked pretty clearly. And that's what really started it.
>> And then somehow you made your way into medicine and research; what really got you interested in health -- human health?
>> Yeah. And that's a great question, too. Because I knew after that summer of junior year of high school that I wanted to be in science that I spent that summer -- later that summer, so it was three-week program. I was a very busy junior. Think about it, I'm a junior in high school, and then I went and spent three weeks in studying where people were doing a very early project on cardiology and they were doing testing on how to make early stents. And so I got to stay for three weeks in a lab, watching people design these struts for stents. And I got very interested in wow, so what I just noticed about the saltwater and the wildlife, now I almost see a one-to-one relationship with the size of this stent and the ability to preserve blood flow in a heart. So that, then, made me realize that I think I kind of want to be a doctor. And I know I want to be a doctor enough that I applied to an accelerated program where I got into med school in high school.
>> Wow.
>> So in high school at my senior year, I had gotten into all the four-year colleges that one would hope to get into it, but I chose specifically to attend a seven-year program which combined three years of undergrad and four years of college all -- four years of med school -- all into one. And that early on made me realize that I knew I wanted to be a doctor and I wanted to sort of get there. And during that path I also realized that being a doctor is not just being a scientist and being very good at being a doctor. There's something about you being a holistic person and a human and able to relate to people and your patients. So I took a year off during that time in undergrad and I spent a year at Oxford, and I studied both humanities and science. And I tried to well round myself a little bit. And that was possibly one of the best things I could have done. Because then I came back charged for medical school. And then in medical school I had a mentor during my first year say, "You know, there's a lot of imaging going on right now, and you said you like photography and you said you like science. Why don't you come and start taking images of the heart with us?" So first year to second year of medical school, Dr. Allen Wasserman, who still remains a close colleague to this day and a close friend, had me start imaging the heart. And we figured out a way where you can get how bypass grafts were doing ten years after bypass surgery just with a picture of the heart. And that started my interest in research.
^10:15
So those two coupled the sort of being in medical school and then being a medical imager that carried forth very strongly with me as I left for Penn for residency. And then when I got to Penn for residency, when I was an intern, somebody approached me and said, "You know, you have some research experience, but really, you don't want to be just experimenting on images and, you know, in the lab. You should really learn how it is to do to clinical research in humans." So he took me under his wing. And Dr. Muredach Reilly is his name. He actually asked me a question that I still to this day ask most of the people who are in my lab, "What are you doing for investigation?" People don't ever ask that question. They are kind of like, "Oh, you're here to work, or play, or take care of patients." But nobody ever stopped and asked what are you doing for research? And that, then, became my passion is that I am a good doctor and I'm a good researcher. But when I combine the two, I'm fairly good at both synergistically. And that has sort of paved the way from my transition from Penn to the NIH.
>> Yeah. So you would say you're a physician scientist?
>> I would, yeah.
>> Okay.
>> I used to call -- you know, when I used to refer to myself early on, I would call myself a clinical researcher. But then I realized that clinical researchers can come in many forms, you know? You could be a social worker studying the determinants of something in a rural population and you're a clinical researcher.
>> Yeah.
>> So then when I started thinking about myself as is I'm a physician first and a scientist second, and therefore, physician scientist captures that very well.
>> Oh, okay. We might go back to get into how you got to the NIH. But before I bury it too late in the conversation, what do you do here at the NIH?
>> Oh, that's great. Yeah, that's great. So my name is Nehal Mehta. I'm a preventive cardiologist, a nuclear cardiologist, and a lipid cardiologist -- all formally trained. And I'm a genetic epidemiologist who took all of those and started a section here at the National Heart, Lung, and Blood Institute, the section of inflammation and cardiometabolic diseases. So my interest lies in an overactive immune system and the immune system itself leading to heart disease and diabetes. And I run a large cohort of patients here, as well as at Penn. And I have a practice at GW. And I have a few places where I recruit patients who have inflammatory diseases and I teach them about their risk for heart disease and diabetes. So that's my current position here. We have a lab, and we have an imaging program, and we have a clinic.
>> What questions are you trying to answer now? What challenges are you addressing?
>> I think the biggest question fundamentally -- and I'm glad you brought it up in that regard -- is that when I arrived in 2012, I wanted to show that remote areas of inflammation in the body, in your teeth, in your scalp, in your knees, on your skin, even in your gut -- I wanted to show that that local inflammation has systemic consequences. So that was my first three years at the NIH, was showing that using psoriasis as a model of disease, I wanted to answer whether inflammation remotely led to a vascular abnormality. And we found that in 2015. We published what you see on the outside in skin diseases is pretty much mirrored as blood vessel disease on the inside.
>> Interesting.
>> But the current question really, then, would be, "Next then what? If you treat that, would the heart disease get better?" So if you treat the skin disease, so that's our major question right now. In fact, today one of my medical students is at the Society for Cardiovascular Angiography and Intervention, SCAI, in San Diego, presenting a late breaker oral abstract on answering the question what if I treat your skin disease with psoriatic medicines, does heart disease get better? And the answer is yes. I thought that would take a decade, it's taken five years. And that, again, dovetails with the intramural program.
>> And so you show there's in the something else going on in the body that's both causing heart disease and skin inflammation, but it's actually some inflammation on the skin that's causing the heart disease?
>> Yes. And that is a very, very astute question. We don't know.
>> Okay.
>> Is it bidirectional, unidirectional? I don't know. Directionality, I won't be able to say. I can say today there's a positive association that when I treat, one gets sort of better and one gets worse. So if I don't treat somebody, it's going to go in one direction. But what I could say is that what we've learned is that we think beyond those other factors that we treat heart disease with, we think that the skin is contribute to the vascular phenomenon. So let's say heart disease was -- right now I can tell you explain about 60% of one's heart disease. It comes from diabetes, hypertension, smoking, high blood pressure, or family history. One of those five things will explain I would say 52%. Now we in the field, thanks to work here at the NHLBI, as well as from our colleagues at other places -- we now know that the extra risk is inflammatory, and genetic, and metabolic. So obesity. So we don't know whether our discovery is, in fact, all due to the skin disease getting treated. But what we're seeing is that treating the skin disease gives you as much benefit as taking a statin medication.
>> Oh, wow.
>> That's pretty crazy, right? The oh wow is pretty crazy because people are like, "Wow, statins can cure all heart disease?" Well, not really. It can take your risk down about 40%. I'm telling you now that treating your skin disease takes that risk down the same amount. So could you imagine my next five, seven years are going to be treating now both the heart disease risk factors and the psoriasis? Could you imagine if we mitigated their cardiovascular risk? That would be exceptional.
>> Because statins have negative side effects, I believe. But if you treat the skin, sort of a positive side effect is --^*
>> They feel better, that's exactly right. They feel better, look better, and less heart disease, right? There's a lot of questions left to be answered, but our biggest one is does treating remote inflammation impact heart disease? And we're, I would say, chipping away at that. We have good observational data, like what we are presenting right now in San Diego is observational. We watched 45 people over a year consecutively. We watched them, right? It's not that we brought them in and did a randomized interventional trial -- that's next.
>> Oh, okay.
>> And that's 2020. So I'm thinking in 2020 now I want to start this idea of running a large, simple trial of saying, "Well, we need to randomize people to aggressive psoriatic therapy versus not and see whether their heart disease gets better. Because right now we might be treating a certain type of patient, and that's why their heart disease is getting better, right? There's a high-risk patient that comes in and I feel like they're very high risk. And I treat their psoriasis and their heart disease gets better, maybe it's because they were high risk that their heart disease got better, right? So I have a lot of remaining questions, but our big ones that we're answering now are remote inflammation, treating it, does it get heart disease better? And I want to remind you, Ben, we're using this as a model -- psoriasis is a model disease for us, meaning our findings of accelerated macrophage oxidation or accelerated neutrophil NETosis -- all of these observations really come down to the fact that psoriasis is possibly just generalizable to other disease processes, that we may find along the way that these cell types, which were never thought of garden variety coronary disease -- they may be at play but we never thought of it. So that's what I think we're learning is that our psoriatic model has now been replicated in lupus. There's a group here that I work with and I do all of this in lupus. Our psoriasis work has been replicated in HIV, and I've been involved in the inflammatory dysfunction in HIV. Our inflammatory model has been moved over to rheumatoid arthritis, which is actually an older field than psoriasis for heart disease. So we think that these are broadly applicable.
>> Cool. So have you published anything or do you have theories that you can talk about, about what is it that's happening in psoriasis that's driving cardiovascular disease?
>> Yeah. And I think that, you know, it's at this time that you are happy that we're not in front of a projector and a PowerPoint because there's a conceptual diagram that we put together that's a -- it's basically a classic hub and spoke diagram where you have this center, psoriatic cardiovascular diseases, and then around it are nine or ten different things we think that are involved in that. If you were to ask me and put me in a position to say, "Pound your fist on the table and say what is it," I would say the biggest problem is systemic inflammation. And that's systemic inflation is driving three abnormalities. The systemic inflammation is driving a metabolic abnormality. So these people are insulin-resistant and behave like diabetics before they have diabetes. So we think that's one. The systemic inflammation is driving cholesterol dysfunction. So you and I have cholesterol levels. And in psoriasis those levels may be normal. But when you take their HDL, which is supposed to be a protective marker, and you look at it, their HDL actually works about 25% less effective in pulling out cholesterol from the body. So we think it's called inflammatory lipid dysfunction. We also think and the biggest reason I think at play is that inflammation is driving fat dysfunction in the body. So 65% of our 400-person cohort -- so that's 240 patients -- are obese. And I shouldn't be the first one telling a patient that they're obese, but frequently I am. And I look at them and I say, "Look, your body mass index is 31, and that classifies you as obese."
^20:10
And they look all the me like I have three heads and they say, "Whoa, whoa, whoa. Wait, wait, wait." So I think that the inflammatory drive of systemic inflation that has its own comorbid diseases, you have this inflammatory dysfunction, this metabolic dysfunction, and this lipid dysfunction, and it's all kind of coming together in my opinion in the fat. And we had a paper published about a month ago, very beautiful editorial written by a group at Hopkins, showing that maybe what you brought up in this interview, that maybe it's that these two are driving each other through a third depot. And maybe that depot is the fat. So we have a paper that showed when you look at the fat in these psoriatic patients, not only is they have a little bit more fat, but it's the bad fat. It's the fat that's called visceral fat; it's all around their organs. So I think what we need to be doing is focusing on education and prevention from these patients getting obese. Right? So what I like about the current -- you asked about our publications and what do we have theories on. This has gotten to a point where the World Health Organization has used our data to call psoriasis a serious autoimmune disease. Because it has a lot of off-target things that we can treat. What I think we need to think about is that when you look at the work that's come together, it really targets one area, which is metabolic health. And these people, if they are obese, that obesity is driving a lot of their heart disease. So the question then becomes well, why are they obese? And then this goes back to your question, is which one's driving which one? I think we need genetic studies to answer that. That is there a genetic predisposition to psoriasis? The answer is yes. Is there a genetic predisposition to obesity? Yes. Is there a genetic predisposition to heart disease? Yes. So maybe there's a genetic predisposition that is collecting in this psoriatic group, and our program is hopeful and very hopeful that while we treat this disease and expand our understanding base, understand what this is due to, that we may, in fact, start targeting the disease differently. Maybe we need weight loss agents. Maybe we need to start using anti-diabetic drugs earlier. Maybe we need to treat their whole being as being diabetic and having heart disease. These are very weighty questions because I don't want to scare my patients. I don't want to make them -- like, I want to make them aware, but I don't want to make them fearful, right? So I think those are our big theories now, is we think it's in the fat. We think that there are immune cells that we are chasing. And, again, psoriasis is treated with biologic therapies, which quell the immune system -- the psoriasis goes away, does the heart disease go away?
>> Is psoriasis associated also with being obese?
>> So yeah. So, you know, the paper -- what got me most interested in this field is in 2006 I was studying why obese people had heart disease. So I was a fellow at Penn. And I look at my schedule in clinic and I would see it. And then I would look at my patients and of the 16 on my schedule, 14 would be obese and 12 would have heart attacks. Not heart disease, heart attacks.
>> Wow.
>> So there's something about being obese that drove heart disease. Right? So from my standpoint I got interested in that aspect of the obesity and the fat. So I guess looking back now, what things can we say? In 2006 they published a paper, my collaborators published a paper that there are more risk factors in psoriasis. So these people have more hypertension, more diabetes, they smoke more, they have more family history, and they have high cholesterol. So one astute person may ask, "Well, it's all due to the risk factors; it's not the psoriasis." So in 2006 there was a paper published by my colleague, Joel Gelfand, that showed if you controlled or adjusted for those risk factors, psoriasis still gave you about a 1.5-fold increase, 50% increased in the first heart attack. And that first heart attack comes between the ages of 40 and 45.
>> That seems early to me.
>> Very earlier. Average heart attack comes 65, 70 in this country. This is 20 years early. So yes, psoriasis is associated with obesity. Yes, psoriasis is associated with all of these heart disease risk factors. But when one uses epidemiological approaches to adjust for those, there's still something about not only severe psoriasis. Even if you have mild forms of the disease, less than 3% of your body, less than three palms of your body, you still have a 10% increase in heart disease. So it's not trivial -- 10% to 50% of the risk of that population is in psoriasis leading to heart disease. So that observation led me to switch away from obesity and study inflammation. And in 2008, we actually got a grant to study psoriasis as the inflammatory driver of all of this using nuclear techniques. And 2012, I kind of say to Dr. Gelfand, "I do believe there's something about psoriasis itself and we need to figure this out." And that's what borne the program. We did not understand how complex it would be. We thought it was going to be a little bit more simple. And we've taken multiple approaches to figure this out, all the way ranging from large human clinical trials, which we have five, all the way down to pre-clinical studies in in vitro cell lines derived from patients, which we just got published in JCI Insight. So we've looked for macrophages out to treatment, and it's complicated, you know? Yeah, we do know there's a link, but we don't know why. So in that regard, we're now undertaking the world's largest sequencing project of these genomes. And we're in the process of getting all of that submitted very soon. Because what if there is some difference in their genome sequence that is having them respond differentially to these environmental stimuli?
>> Cool. And so you mentioned a couple of the actuals that you use. So what techniques, advanced technologies do you have access to that you make use of in your research?
>> You know, it's so interesting. So I came from University of Pennsylvania where it is a rich environment for research and translation. It's first in human -- in a lot of respects. I came to the NIH because of the tools, of the ability to really advance science in my opinion exponentially. Not any other way -- not linear, exponentially. So the tools that I use -- so what we have is we realized that it's hard to find patients with psoriasis who are untreated, biologically naive, and flaring because most people will actually get that treated before they find me, right? So what we did was we started a cohort study. Anybody with psoriasis, anywhere in the country can write to me and say, "I'd like to enroll." If you're 18 to no age limit, you can come in. And what tools we use are very careful translational medicine tools. So we will get blood, skin, and fat from all patients. From the blood we isolate immune cells and lipids. We have an FPLC in the lab, so we can isolate down to their actual lipoproteins. And then we use tools that include nuclear imaging, coronary CT imaging, aortic imaging, vascular functioning testing. And we use those to make the phenotype. We're not going to wait for these people, Ben, to have a heart attack. That's what I don't want [Laughs]. Right? So my cohort, if you look at the average age, I on purpose recruited patients between the ages of 35 and 45. So the average age of our cohort right now is just over 45 years of age. And the reason is, is that's when they're going to have their heart attack if they have one, right? And the tools we use is longitudinal follow-up. So we have them come in at baseline, whatever treatment they're on, year one, year two, year three, and year four. And we have four years of follow up of imaging data in these people. We have their cells and their blood all throughout. We use gene expression, RNS sequencing, single cell transcriptomics, flow cytometry. We use, like I said, hot liquid chromatography. We've also used in many instances a liquid chromatographer mass spec. So our most recent discovery came by way of using mass spec to look in the skin and the blood. And we've discovered that psoriasis is not a disease of hyperinflammation alone. Psoriasis itself may be a disease of being unable to turn off the inflammation. So a disease of an anti-inflammatory nature. So that's work led by one of my post-docs in the lab just published in ^ITJournal of Investigative Dermatology^NO. So the tools that the NIH have literally skyrocketed what we are able to discover. And I have to highlight one other piece of work that we've been lucky to pull into our lab. There's a talented post-doc scientist who knows how to use electron microscopy. And so we for the first time now have discovered that the skin itself organizes in a way similar to blood vessels. Once the blood vessel starts getting damaged, you start seeing organizational layers. And what she has found is that in the skin and in the blood vessel in psoriasis, these layers are filled with crystals -- crystals, cholesterol crystals. And what we're trying to understand is why are there cholesterol crystals in psoriasis lesional skin that are not in normal skin? And why are we finding them in the blood vessel as well? So these tools -- microscopy, immunohistochemistry, live sort of phenotyping. What you're able to do here at the National Heart, Lung, and Blood Institute is simply down the hall is a place where I see my patients and I recruit. And I get sample and specimens, and I bring them back to my lab, and I catalog them and I prep them. But within one hour, we're using real, live human specimen live. And that is extremely difficult to do on a busy urban campus where you might be a mile away from your freezer, right? So you're already thinking, "Wow, neutrophils are becoming active, proteins are degrading, I can't do this." You can do it here.
>> Yeah, you're right here in the clinical center.
^30:31
>> I am right here, and I love that. I love that. So you asked about tools. But -- and I can go on. I mean, we, again, use cutting-edge human quantification tools. So I gave you all my basic in vitro stuff. If you look at what I'm doing in humans, it's I get a standard CT scan and I have this vision of having a one-stop-shop. If I can give you with a single tube of blood and one quick image your snapshot risk of ten-year risk of diabetes, heart disease, I've done you service.
>> Yeah.
>> And I really want to do that. And so I have another lab, an image quantification lab. And Dr. Balaban has to get a lot credit for the way he has allowed me to set up my program that I have the ability to do quantifications serially on images that people usually will look at, give a clinical report, and say see you later. We dissect those images like you would never believe. And that has taught us that these blood vessels actually are eating themselves. There's a necrosis going on not seen in non-psoriatic diseases. So this has now become our new kind of line of questions. Now we know the blood vessel's affected; how and why? And that set of tools? Second to none. I have collaborators here, David Bluemke, Peter Herscovitch, Mariana Kaplan -- these are world leader in their fields, and I have access to bring their knowledge base into psoriatic inflammatory atherogenesis. Right? And it's just a very, very good way of growth.
>> Cool [Laughs]. And are some of those collaborators at other institutes within the NIH Intramural Program?
>> They are. Yeah. I'm glad that you brought up that. So I brought up David Bluemke, who is an NIH clinical center. He has just recently left to become the editor-in-chief of a very grand journal. Mariana Kaplan is at NIAMS, so the Arthritis Musculoskeletal Institute. I have an NCI derm collaborator, Dr. Edward Cowen. And then I brought up Phil McCoy, who's in NHLBI with me. He's the director of the Flow Core. And then I work with NINDS on some brain imaging for depression and amygdala sort of hyperactivity. And, again, it's like having unique universities sitting right here, right? But I have to say it's not without its effort, you know? You have to actually make that effort to say, "This is what I'd like to do." But people around here want to do it. We're paid to do science. Right? I'm not paid to do anything, I'm paid to do science, right? Science. And everybody here feels very privileged to be paid to do science. And that's intramural program, I think.
>> Yeah, and there's people doing every kind of science here. So whatever you can dream of, someone can probably help you with it.
>> That's exactly right. And I have some crazy ideas -- I brought up one this morning right before this interview and I had a crazy idea. And I met with my colleagues across the street, extramural, the people who give the grant money out to kind of get a finger on the pulse. Be like, "Hey, what do you think?" And it's a real nice sounding board. And to say that extramural folks are very eager to hear what's going on intramurally because we are creative and we have these crazy ideas, there are people all around that want to just sit and talk about science. That's unique. Right? There's not the pressures of other things that are diffusing us away.
>> And so you're -- you're in the first class of what's a very interesting program here at the NIH, the Lasker Clinical Research Scholars Program. And that was, I believe, six years ago now?
>> Yeah.
>> And you're sort of coming up on a crossroads. Can you maybe talk a little bit about why you applied to the Lasker program and what it's been like and/or what's coming up next for you?
>> Yeah, that's great. So it's an interesting thing. I think one of the things that I've been lucky about is I try to surround myself with nice people who are good. It's not that they are good and then nice -- I start with nice. And that's very important. And, you know, my lab will joke about it that the first question that Nehal asks in an interview is, "Are you nice?" Because I don't like to be around mean people. I'd rather be you were nice -- you may not be the sharpest knife in the drawer, but you're nice. Let's start there. If you're good and you're nice, I think one of the things that I would say about the Lasker Program is I was informed about it by my former lab chief. So Dr. Murdock Riley and Dr. Dan Rader, who mentored me for these four years at Penn after I became a clinical cardiologist, they brought this to my attention and said, "Look, you have a very good program." It was at the time that I had written my first randomized trial. I had gotten it funded as an ROS mechanism, which is a big extramural grant. And I was at a crossroads then in '12 -- or this was about '10 when I'm writing the grant -- and I could have gone one of two ways. I was told about the Lasker Program as being the place for somebody who does clinical work to do science. The NIH clinical center is the world's largest research hospital, and it will -- it will literally help you do the science you want in humans. So that intrigued me. And I took an idea based on my RO1 and I wrote my cohort and I said, "We need to learn this." So I left Penn a little bit uncertain because I had been raised there as an intern. You know, my wife had been there as a medical student. We thought we were going to, you know, grow old there together. But I came here because of the opportunities that the Laskers offered. And that was five to seven years of coming to the NIH and doing clinical research that nowhere else could be done. The second phase of that have program is now I can take $7 million or so with me and I can go to an extramural university and start another, or start a research program, or bring my program over. The way I see these things is I just think it's too early to tell. I have a year to decide of what I'm going to do. It's too early to tell what direction things are going to go. You know, I've been teaching my three-year-old this that, you know, if you actually smile and care and be passionate about what you do, you'll definitely get the notoriety that you need personally and professionally. I don't think that that's an issue. But the Lasker Program now puts me in a difficult position because I don't want to leave. There's no reason to leave. But you sometimes wonder the growth of a program, right? The next phase of my program would be doing the 1,000-person clinical trial to prove my first in-human discoveries. And that's where I am now.
>> Yeah.
>> I don't know if intramural NHLBI is the right place to do that trial. Do I believe it is? I do. Because I made the discovery first in-human and it's ours to actually bring out to the public that we made this discovery. Do I think that bringing 700 people to the clinical center is the right way to use the clinical center? I don't. I actually think that there's a way that we can partner with academics and with industry to do something like this. So I would say to anybody who's thinking about the Lasker Program, if you have a shot at applying, apply. It will allow you to see exponential growth of your program in a very short amount of time, but it will also leave you very spoiled. Because the NIH intramural program is the most magical inspiring place on Earth. I come to work every day with a huge smile, with so much energy and passion because everybody here is working towards a common goal. We want to understand inflammatory atherogenesis, and we want to stop it. And I think that that is very powerful. There is no other mission in my section than that one, right? When you look at other mission and plans or you rook at other strategic plans, there's always something else buried in there. Not here, right? So that was my thought of the Lasker's. And now do I sort of think that it's going to be here forever, and if I stay, is it bad? I think it's great no matter what happens, that if I go do the trial elsewhere or I stay here, it doesn't matter. The other piece that the Lasker Program has stamped me is the ability to talk to former Lasker awardees. So I have had the privilege of calling up Tony Fauci, Harold Varmus and saying, "Hey guys, I'm not sure what to do here." And you get access to people who you would never, ever have access to. So I think it's a great opportunity.
^38:43
>> Very cool. Do you have any advice for anyone who is thinking about applying to the Lasker Program or alternatively, advice for someone in high school or college thinking about going in to become a physician scientist?
>> I would say -- I'll answer that in two parts -- I would say that for those who are entertaining a career in science, find me. Find someone like me. Find someone who has made a active decision to pursue a question rather than a career path. I'm very question-based. Find somebody to talk to about what your interests are. A high schooler should come to the NIH for a summer. Someone in college should spend some time in a lab. Explore that. I have found my biggest successes are knowing what I don't want to do.
>> Oh, yeah [Laughs].
>> Right? I know what I don't want to do. And that's an easy way. Because, again, I'm teaching my children process of elimination. It's a great thing. I know I don't want to be in an operating room 12 hours a day. Because I could have been. I know I don't want to see a full battery of patients because I know I could have been. I know I don't want to just do science because I love patients. So you need to make your own sort of thing and you have to learn that. Okay. Number two, for Lasker's I would say if you're thinking of applying, the thing that they should get advised about is what is it about this environment that's going to trajectory you the way you think? For me -- I'll be very specific, Ben -- I wanted to use PET MRI. There were three in the world at the time -- one was at the NIH, one at Germany, and one had just got installed in Boston. I was going to be one of three people using a tool that would phenotype my blood vessels better than ever before. So my advice to future Lasker applicants are look at the clinical center. What is it that you can fashion here that you can't do at your own home? And if that answer is one or five, apply. Because there's certain things you just can't do. I have the vision of putting a new tracer into humans to tag a cell -- there's as facility downstairs that is here called the Probe Development Center.
>> Oh, yeah.
>> That will make that probe over a period of time when I give them enough in vitro materials. That process could take up to five years and $2 million on the outside; we can do it here as a collaboration. So my advice to the Laskers is make sure you look into the opportunities that you're looking to and then go from there.
>> Uh-huh. Cool. Were there any mistakes that you made in your path that maybe didn't turn out to -- maybe they even had a positive effect, they seemed like a mistake at the time but maybe they were just mistakes [Laughs].
>> You know, it's interesting. When I was interviewed by ^ITNature^NO for Turning Point -- and it's interesting, it was a very similar question that they had asked. But they asked it differently, and I'm going to give you the answer I gave them. I was three credit hours away from getting a PhD.
>> Oh, wow.
>> Three. Which would have been one course and one independent study. And I was offered to do that. But it would have required a year the way the courses were set up. And at that time, I thought long and hard and I said no. And do I think that was a mistake or a regret? I don't, but sometimes it does come up into my mind, would I have more street cred if I had a PhD? Right? And so those types of thoughts are maybe along the way something that I would say is a regret or maybe a decision that may have -- may have had some impact, but it hasn't affected me. You know, I'm still a clinician scientist, a physician scientist. I have a master's of science in clinical epi rather than a doctorate in epidemiology. The other thing that I would say along the way is I wished I learned a little bit more coding and engineering, but that wasn't a thing when I was growing up. So I've become a very big proponent of coding and understanding how things work from an engineering standpoint. Because if I had those skill sets plus the skill sets I have, I think I would probably be able to do more biomedical engineering. And so that's one of the other regrets. But that's not even a regret, I can hopefully find someone to work with me on those things.
>> Sure, yeah.
>> But along the way, no. I would say that I'm glad I did the things the way I did them. I did take a little bit of a circuitous path. You know, by the time I graduated residency, I could have been a spine surgeon. I was a PGY9. People laughed at me, knowing that I'd been there from 2001 to 2010 as a resident. Most residents are there for three years, I was there for nine years. But it's okay. You know? At the end of the day that felt like a mistake when I was doing it, too. But it all ended up really great.
>> Well, let's see. Is there anything else that you might like to mention about your research that we might not have hit on or about the intramural program that's been good?
>> No. I think that one thing that should be made, you know, sort of pretty apparent in this is that my involvement with the intramural research program has shown me that there are things that seem unchangeable, like people say, "That's not going to change," but if you are passionate and you have truth, and you have evidence, and you have support, you could make change. Because the IRP has been here a very long time, and we've been doing great science for many, many, many years. And it inspires me, like I said, to come here every day. But there are things that aren't perfect about the place. But it changes. And the change is possible. And the outside world should know that there is a place on Earth that is purely dedicated to science. And even though it seems like things are hard to change here, they can change. And we can make that change happen. We are the largest clinical research imaging translation program in the world. The NIH helped me do that. And they never thought that was possible? They thought what, 19 procedures on one patient in two days? That's not possible. Let's do it together, right? We do a PET CT, PET/MRI, a coronary CTA. We do vascular function tests. We do all of it in one morning. We do fat, VAT, all the characterizations. It was possible, it took some change. So I would say that people should remember that even though things seemed fixed, there's always room for change if you actually have that passion and that drive. So I would say come visit the intramural program, you know? Like, that would be my message to anybody who has, like, sort of a wonder about it. Just come visit. You know, there's plenty to do. There's great seminars on campus. And then I guess the last thing that I would say is I don't feel like I go to work every day. And I think that that's important for somebody to hear. That because I have become so intertwined with work becoming what I love and what I do, that I never feel like I'm working. And that's an important thing for people to remember. And I don't know how to impart that on people who don't understand what being a physician scientist means. But I just have come to a point where I've learned how to see a patient and do research at the same time.
>> Yeah.
>> Right? So I'm doing service to the person, but I'm also doing service to the field.
>> Yeah.
>> And that to me is something that people should really keep in mind as they try to understand physician scientists. If you can marry the two, it's like a match made in heaven.
>> Thank you for listening. That was Dr. Nehal Mehta. To learn more about IRP research, as well as the work of Dr. Mehta, please visit irp.nih.gov. And make sure to subscribe to our weekly newsletter for the latest updates. Have a great one. Bye.