Moving the Needle on Inflammatory Diseases and Setting a Course for Research Growth
Joe G.N. “Skip” Garcia, M.D., is associate vice president for research at UF Health, professor and director of the Center for Inflammation Sciences and Systems Medicine at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology. From his lab and offices in Jupiter, he is helping advance clinical translational efforts at UF Health and The Wertheim UF Scripps Institute. Garcia recently discussed his research and vision.
Q: What did you see in your own practice of medicine that made you want to dedicate your focus to inflammatory lung disease?
A: I’m a Latino from Texas. I wound up growing up in coastal California. When I was a kid, age 11 to 15, I picked strawberries and cut lettuce right alongside migrant farmworkers. That’s where I knew I wanted to go into medicine. But as far as being a scientist? I never remotely imagined myself doing that. There is this term for physician-scientists like me, the term is called “late bloomers.” I was definitely that.
I liked pulmonary care medicine. I liked being in the ICU. I loved being an ICU doc, taking care of the sickest people on the planet. When I did start my nascent research career, it was to investigate ARDS, acute respiratory distress syndrome. This is a syndrome that when you go into the ICU and you have pneumonia or sepsis or COVID-19, and you have respiratory failure, you need to get intubated. You get put on ventilator. Your mortality is about 40 percent. So it’s a bad, bad disease. I was focused in my research career to try to move the needle on mortality.
Q: What led you into research, and to your key discoveries, was it gene expression profiles of these ventilator patients at Johns Hopkins?
A: The story of how that all happened is, I didn’t know what genomics was, really. I am in the ICU taking care of ICU patients at Hopkins and I get a call from a guy. He says, “Hey, Dr. Garcia, I’m a professor at Hopkins in the neurosciences. My dad is in the hospital”…I got to know the son, George R. Uhl, M.D., Ph.D.. It turns out he was one of the first adopters of microarrays, which was a gene expression profiling technology. I went over to his lab, and he showed me. I fell in love with that technology.
I got to be really good at it. We were one of only 10 places in the country that got a Program in Genomic Applications grant from the NIH, and I was the principle investigator. I was linking good, tight phenotypes to agnostic genome-wide expression profiles. This one gene, NAMPT, kept being at the top list of every experiment we did. There were no papers on it, nothing that linked it to inflammation. We went after it and now we are the world’s authority on this protein. And it turns out that it is a very novel regulator of inflammation that is critically intrinsic to innate immunity. And we have an antibody against it that nobody else has, and so now we have a therapeutic. I’m very proud of that.
Inflammatory gene expression in mice changes dramatically when the eNAMPT protein, an inflammation master-regulator, is interrupted by an antibody therapeutic Garcia’s team has developed. / Journal of Translational Autoimmunity
Q: When the announcement of your recruitment went out, it said that your experience and work will help The Wertheim UF Scripps Institute accelerate our ability to move research discoveries into clinical advances for improved patient care options. Can you elaborate on that?
A: You have 40 some scientists whose research is terrific, but their connection to academic and translational medicine right now is not as meaningful as it could be. Medicine has become team science. The team has a lot of smart people. I think in the future for Wertheim UF Scripps, or some entity like a Jupiter Med-UF Health facility, they are going to have the capacity to bring in more MD-scientists. That will be a very, very, very good thing. It allows you to build programs. It helps scientists here have access to human samples. It’s really an important thing for translating your particular findings. There will be a lot of upside. I totally get how impactful it is to have the kind of scientists that exist here right now. What we’re talking about is how to leverage that.
Q: What does that look like? How do you leverage that?
A: It’s multifactorial. You get scientists together. Have them start working together. You know, I’m really good at NIH P01 program projects. I’ve had one for 30 years, I’ve sat on the review committees. I’ve had two at a time for most of my career. And what really looks good on a program project is when you recruit somebody else from outside who brings some good science and that you collaborate with. It has to be meaningful, it can’t just be superficial. If you are collaborating and publishing with that person, that really makes you look strong. And so the opportunities exist for both Gainesville program projects and, there are few P01s on the Wertheim UF Scripps campus, and so, I would look to see that change.
Q: Tell us more about your plans for the Center for Inflammation Science and Systems Medicine.
A: We have a lot of work going on in multiple domains. A fair amount is based on further understanding how NAMPT works and how it is secreted. I also do lots of collaborations around genetic epidemiology of diseases. How do certain patient populations have risk for diseases. There are a lot of people who have diseases like non-alcoholic fatty liver disease. You can’t treat them all with an expensive biologic. You need to understand, how are you going to identify the right patient who would benefit most from that therapy? What increases risk? What are biomarkers. It probably starts with metabolic syndrome. Type 2 diabetes. Inflammation plays a serious role in in making that fatty liver an inflamed organ and then a fibrotic organ. And then you have risk of cellular carcinoma or cirrhosis. Not everyone is going to develop that, but you are on the road. It is a preventable disease with the right therapeutic.
Q: How important is the Wertheim gift to the campus?
A: It is transformative for sure. The opportunity of blending and elevating the education mission, the research mission and then ultimately having the resources to link it to the clinical mission? That is the promise of the Wertheim gift. The impact of the gift is immeasurable.