On the heels of receiving nearly $10 million from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Rohit N. Kulkarni, MD, PhD, discusses how his team will use this grant to pursue new approaches to studying type 2 diabetes and obesity by exploring gene expression and regulatory activity in multiple metabolic cells.
Rohit N. Kulkarni, MD, PhD, believes without a doubt that the quality of care for people with diabetes has progressed rapidly over the last three decades. He anticipates his newly funded research will lead to new discoveries that will continue the progress to improve lives.
Kulkarni is the Diabetes Research and Wellness Foundation Endowed Chair and co-head of the Section on Islet and Regenerative Biology at Joslin Diabetes Center. He and his collaborators were recently awarded nearly $10 million from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to take a new approach to the study of type 2 diabetes and obesity.
The five-year grant will support Kulkarni’s research examining gene expression and regulatory activity in multiple metabolic cells — specifically alterations to messenger RNA (mRNA) — that lead to the development of type 2 diabetes and obesity, with the goal of identifying potential targets for innovative treatments for the chronic conditions. Kulkarni is the principal investigator on the collaborative study that includes co-principal investigators at three additional institutions: the University of Chicago, University of Kentucky, and the University of Pennsylvania. Their research project is entitled, “Epitranscriptomics in human obesity and type 2 diabetes.”
Endocrine News spoke with Kulkarni about his groundbreaking collaborative research study and what he thinks about the current state of diabetes care and discovery.
Endocrine News: An NIDDK grant award of nearly $10 million can be career changing. Can you share your initial reaction when you heard the news?
Kulkarni: We were thrilled and excited because it’s a very competitive grant and we’ve been working on the grant for some time, so it is great to know that the NIH finally appreciated the innovative nature and exciting aspect of this approach because it will potentially open new therapeutic avenues.
EN: You are the lead PI are joined on the project with four other co-PIs. Have you previously collaborated with this group of researchers?
Kulkarni: We have been collaborating with each of the groups for various periods. With the group at the University of Chicago, my lab started some of the initial work focused on this new approach over 10 years ago. We have collaborated with the group at Pennsylvania for more than six to eight years, and with Kentucky most recently since a few years ago. So, we have a robust collaborative approach among the teams that has been very productive. And so, it’s great that we’re now all working on this topic together.
“Although it’s a cliché I have realized over the years that we have to view failures and successes equally. I have also learned that when you’re successful, it’s a team effort and everyone deserves credit. And when there are setbacks, I encourage people to use it as a challenge to move forward in a way that will allow us to reach our goals more effectively.”
EN: What are your target numbers for enrollment across the four study sites?
Kulkarni: In terms of human samples, we are pretty ambitious. We hope to target more than 80 to 100 individuals in the context of obtaining blood samples, biopsies for skeletal muscle, and fat tissue. At the University of Pennsylvania, we are working with Professor Ali Naji to obtain human islets. From the University of Kentucky, Professor Philip Kern will assist in obtaining skeletal muscle, adipose tissue, and potentially also liver samples.
EN: How will your team’s research potentially impact the care and treatment of diabetes?
Kulkarni: Many people are aware, and if not, they should be aware that insulin was discovered more than a 100 years ago. We continue to move forward in terms of finding a cure for the disease. Our observations that RNA modifications are playing a role in the context of metabolism are exciting because it gives us an insight into an area which has not been explored at all in the context of metabolism. And so, understanding this aspect of biology and how it contributes to the pathophysiology of both diabetes and obesity, an area that could be common for chronic conditions is very innovative. I feel that exploring this area in an aspect of biology, which has not been touched on before, will give us new insights.
EN: Can you recall the period when you knew endocrinology would be your specialty? Was it a specific occurrence that sparked your interest in this specialty or the research?
Kulkarni: The decision was based on a combination of both excitement of research, and a personal interest considering people in my own family have diabetes. When I was in medical school and subsequent training, it was impressed upon me that, in addition to patient care, one can do a little bit more by undertaking research. This prompted me to take the extra step of getting a PhD in biochemistry when I was in England training as a physician. That provided me with a holistic view about understanding biology in a way, not only to treat individuals, but also to delve into those areas which have been difficult and contribute to understanding them better so that we could finally find a cure for the disease.
EN: You mentioned people in your family who have diabetes. Have you seen a difference just in their care and treatment in the last 10 years?
Kulkarni: Yes, without a doubt, the quality of care for individuals with diabetes has been progressing rapidly. For instance, trying to measure glucose levels in a less painful manner. Also having different types of insulins, which allow for different individuals for different levels of protection has emerged to be important. So, over the last two or three decades, these aspects have improved and made it relatively easier for patients to take care of their glucose levels. However, nobody likes the pain of injections or for testing glucose. So, if we can get an oral pill or something that can be curative of the disease that would be fantastic.
EN: Along that same line, I think the the cap on insulin costs has been a big change in patients’ lives. The Biden administration did it for Medicare patients and then Lilly and other drug companies followed suit and dropped their cost.
Kulkarni: Yes, you’re correct that costs have gone down tremendously. And that is an important component because it becomes affordable, and people are much more amiable for these therapies for better glycemic control and reduce long-term complications.
EN: What has been the most rewarding part of making discoveries with the young researchers in your Joslin laboratory?
Kulkarni: My lab team ranges between 12 and 15 personnel. We have about eight or nine fellows, a few research assistants, and occasional students. The most exciting, rewarding aspect of my job is waking up every day to ask new questions on how to cure the disease. And I think that is always exhilarating because of my own interest in the area, but also equally important is interacting with ambitious and energetic young trainees who come to the lab. I don’t assume that I know everything. And when I get asked out-of-the-box questions from the trainees, my reaction is, “Wow, that’s a very important perspective.” So, I give them the credit and ensure we push ourselves to keep moving forward.
“Our observations that RNA modifications are playing a role in the context of metabolism are exciting because it gives us an insight into an area which has not been explored at all in the context of metabolism. And so, understanding this aspect of biology and how it contributes to the pathophysiology of both diabetes and obesity, an area that could be common for chronic conditions is very innovative.”
EN: What do you teach them about dealing with setbacks in the lab? With your long career in research, how do you tell them how to deal with it?
Kulkarni: Although it’s a cliché I have realized over the years that we have to view failures and successes equally. I have also learned that when you’re successful, it’s a team effort and everyone deserves credit. And when there are setbacks, I encourage people to use it as a challenge to move forward in a way that will allow us to reach our goals more effectively. Not every success is a straight line, and I remind trainees that progress in research is mixed with setbacks and successes. When you fall down, you have to just get up and go forward again.
EN: Last question. Who has influenced you the most in your career?
Kulkarni: I have had excellent mentors beginning with my teachers at school and then during my medical and doctoral training and post-doctoral fellowship. Each of them has provided a unique perspective that has enriched my career and life, and I am grateful for their mentoring and advice. It’s important to remind oneself that it’s a lifelong learning process and the earlier one realizes that each of us would enjoy and be much more effective in what we do.
-Shaw is a freelance writer based in Carmel, Ind. She’s a regular contributor to Endocrine News and author of Laboratory Notes.
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