Q&A: Carmella Evans-Molina, MD, PhD, proud to serve as mentor
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Key takeaways:
- Carmella Evans-Molina, MD, PhD, received the 2023 Outstanding Scientific Achievement Award from the ADA.
- Evans-Molina discussed beta-cell research, mentoring and a future clinical trial in a Healio interview.
When she first enrolled as a freshman undergraduate student at West Virginia University, Carmella Evans-Molina, MD, PhD, never imagined she would become an award-winning diabetes researcher.
Years before conducting research on beta-cell dysfunction and participating as an investigator with the Type 1 Diabetes TrialNet network, Evans-Molina initially went to school to become a pharmacist at West Virginia. After finishing pharmacy school, she enrolled in medical school at Marshall University in West Virginia and later departed her home state to complete residency training at Massachusetts General Hospital in Boston, with the goal of becoming a primary care doctor. However, during the end of her first year of residency, Evans-Molina realized she wanted to do more than just be a physician.
“One day during teaching rounds in the cardiac ICU, my attending gave us a talk about his research, and I was really intrigued by that,” Evans-Molina told Healio. “He was doing all of this very cool research trying to answer molecular questions about cardiovascular disease. His talk really planted the seed of how rewarding it could be to have a career that combined research with patient care. This example led me to get involved in health outcome research, under the mentorship of Elaine Hylek, MD, PhD, during my residency.”
After completing her residency, Evans-Molina became an endocrinology fellow at the University of Virginia and began to combine her desire to conduct research with her interest in endocrinology. Today, Evans-Molina is a top diabetes research at Indiana University, serving as the school’s Eli Lilly Foundation Professor of Pediatric Diabetes; a professor of pediatrics, medicine, cellular and integrative physiology, and biochemistry and molecular biology; director of the Indiana University Center for Diabetes and Metabolic Diseases; diabetes program director at the Herman B Wells Center for Pediatric Research and director of the Islet and Physiology Core at the Indiana Diabetes Research Center. She is also a staff physician at the Richard L. Roudebush VA Medical Center in Indianapolis. Evans-Molina was honored as the 2023 recipient of the Outstanding Scientific Achievement Award at the 83rd American Diabetes Association Scientific Sessions.
Healio spoke with Evans-Molina about her career, some of her pivotal research on beta-cell dysfunction and what the Outstanding Scientific Achievement Award means to her.
Healio: Why did you decide to apply for a position at Indiana University?
Evans-Molina: My first grown-up job was to come [to Indiana University] as a faculty member. My transition to IU turned out in a different way than I might have expected. In academic medicine, you apply for something called a K award, which is a career development award. This grant provides you with mentorship while you’re learning how to be a scientist, run a lab, write grants and write papers. So the very traditional idea with this grant is that you will spend a couple of years near your mentor. Then, you will go to a different institution [and] negotiate for a startup package.
Around the time that I had just received a fundable score on my K award, my mentor, Raghu Mirmira, MD, PhD, went off to give a talk at Indiana University. IU was developing a new pediatric diabetes research program. He came back very excited from this talk and about this great opportunity and said, “You know, I think it would be a good idea for you to consider coming too.” He was being recruited into the department of pediatrics, but there were also open recruitment slots in the department of medicine. I was an adult physician, and they had open recruitment slots in medicine. It actually worked out quite well that I could be a part of this new center, but I could also negotiate independently. I could have all of the necessary startup resources, and I could still very much be mentored as I developed my career.
Now, I can’t imagine working anywhere else. IU is just an incredibly supportive environment. It’s a place where faculty members are valued, where there are plenty of career development opportunities, and there are resources to help investigators. Indianapolis is the place that I now feel lucky to call home.
Healio: Can you discuss some of your work with calcium signaling in beta-cell secretory pathways and insulin secretion? When did you start this research and what attracted you to this area?
Evans-Molina: When I began my fellowship research at the University of Virginia, I was focused on understanding the very basic mechanisms of beta-cell dysfunction in diabetes. In one of my first projects, I had been charged with a project that involved treating mice that had a genetic mutation that led them to have obesity and diabetes with the drug pioglitazone. Pioglitazone had beneficial effects on beta-cell function in clinical trials, and I was testing the hypothesis that pioglitazone may alter beta-cell chromatin architecture or the way genes are packaged within the nucleus, and therefore have a beneficial impact on the transcription of beta-cell identity genes.
It just so happened that my neighbor in an adjoining lab, Craig Nunemaker, PhD, who was also my contemporary, had a particular expertise in calcium imaging. One day, [Nunemaker] offered to perform calcium imaging on islets from the pioglitazone and control-treated mice. Interestingly, there was a profound defect in glucose-stimulated calcium responses in islets from control-treated mice, and this defect was reversed with pioglitazone.
It was actually a reviewer of the manuscript who suggested that we look at expression levels of the sarcoendoplasmic reticulum calcium ATPase (SERCA) pumps in the beta cell. The SERCA pumps are located in the endoplasmic reticulum (ER) membrane and actively transport calcium from the cytosol into the ER. When we performed this experiment as part of the manuscript revision, we found that SERCA expression was indeed very low in the islets from untreated diabetic mice, while pioglitazone-treatment restored beta-cell SERCA expression. So as I was starting my lab, these two somewhat lucky and somewhat serendipitous events led me to ask a completely different set of questions. In follow-up, I wanted to understand at a broader level how changes in calcium signaling within organelles like the endoplasmic reticulum and the Golgi impact beta-cell health and function and contribute to diabetes pathophysiology.
I had another watershed moment in my career when I met Linda DiMeglio, MD, who is a clinical trialist here at Indiana University. Shortly after joining Indiana University, she asked me to be a part of the Type 1 Diabetes TrialNet team. TrialNet is an NIH-funded, international clinical trial network focused on identifying treatments that can prevent the loss of insulin secretion in type 1 diabetes and also delay the onset of diabetes in high-risk individuals. This was a phenomenal opportunity, because it provided me the opportunity to learn about clinical research and to attend TrialNet network meetings. As a scientist, this opened up a lot of new avenues, and I developed a translational research program focused on identifying and validating new biomarkers that might tell us something about the health status of the beta cell in people at risk of diabetes. Now, this goal is a really active part of our research program, and we’ve developed a number of resources, including a local biorepository, to support projects under this umbrella. I’ve continued to learn more and more about clinical research, and I’m excited that I just wrote my first clinical trial protocol on TrialNet. This study was recently approved by the FDA. We’re hoping to start enrollment in the late summer.
Healio: Is there any achievement in your career that you are most proud of and why?
Evans-Molina: Right now, the thing that gives me a lot of joy is helping early-stage investigators and new faculty members who are just starting out. I really love being a mentor to them, being a part of their mentoring committees and helping them think about how they’re going to apply for their next grant and develop their careers.
My focus has shifted. I don’t think about the things that are necessarily something that I might be recognized for, but I enjoy it when they get recognition and when they accomplish something. When they get their first grant, it’s just an incredible feeling. The thing I’m most proud of is that we’ve spent a lot of time and energy growing a cadre of early-stage investigators here at Indiana University that is unique in both its breadth and depth. We have an incredibly vibrant group of outstanding early-career investigators studying diabetes in our center. I’m really proud of the contributions that I have made to growing this environment.
Healio: What was your reaction when you received the news that you would be a 2023 National Scientific and Health Care Achievement Award recipient?
Evans-Molina: It blows your mind a little bit. My second slide [in the ADA presentation] was a list of all the people who have previously won this award. It’s incredible to think that my name will now be included among this list of luminaries in the field. These are the people whose work I devoured and learned so much from as a trainee, and I continue to learn from them as an established investigator. This feeling was followed shortly by the panic of how to put together the award talk. I am a perfectionist, so I wanted every word to be perfect. I wanted to talk about my science, but I cared a lot about recognizing the people in my lab who contributed to the work. I wanted also to acknowledge all of the important mentors and collaborators in my career. It was just a ton of emotions, all of them so very special. As we got closer to the meeting and during the meeting, I enjoyed all the notes of congratulations from colleagues and past award winners, and I really enjoyed celebrating in San Diego with my lab and my colleagues.
Healio: What are you currently work on and is there any research you’re planning to do in the near future?
Evans-Molina: The thing I’m most excited about this summer is getting this clinical trial up and running. The name of our study is the JAKPOT T1D Study and we will test two JAK inhibitors, abrocitinib (Cibinqo, Pfizer) and ritlecitinib (Litfulo, Pfizer) — to see if either or both can preserve insulin production in people newly diagnosed with type 1 diabetes. This is exciting to me because a lot of preclinical data indicates that JAK inhibitors can impact the dialogue between the beta cell and the immune system during the development of type 1 diabetes and that these drugs may turn off stress pathways in the beta cell that contribute to diabetes development. I am excited from a scientific perspective, but I am excited also for the opportunity to grow professionally as the study chair of this trial.
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