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Penn Medicine’s Juan Alvarez, PhD, Explores Replacement Therapies for Insulin-Dependent Diabetes

A headshot of Juan Alvarez, an assistant professor of Cell and Developmental Biology, standing in front of a window

Juan Alvarez, PhD, an assistant professor of Cell and Developmental Biology, joined Penn Medicine in January 2022 to continue his pursuit of new diabetes therapies that don’t require patients to inject or pump insulin into their bodies.

“I’ve had a pretty interesting run,” says Alvarez, who was born in Guatemala, where he completed high school before attending an international high school in Italy. From there, Alvarez traveled to the United States to complete his undergraduate degree in molecular biology at Princeton University, his doctoral degree in biology at the Massachusetts Institute of Technology, and postdoctoral studies at Harvard University.

Why Penn Medicine? “I wanted to be in a diverse city where there were large communities focused on my areas of research,” he explains. “I have my feet in two sides of the river — one leg is in circadian biology — or the study of the 24-hour rhythms that are natural, internal processes that regulate the body’s sleep-wake and feed-fast cycles — and the other is in diabetes. Penn has one of the largest circadian biology communities in the country and it also has a very large diabetes community. I found myself ideally located in between, bridging the two shores of the river.”

In this Q&A, Alvarez describes his current research and the inspiration behind his work.

What research are you currently undertaking?

Our laboratory is focused on studying how circadian rhythms shape metabolism, the chemical reactions that change food into energy, and the maturation of pancreatic islet cells, or the group of cells that control blood glucose levels. To do this, we use human stem-cell derived pancreatic islets and mice as model systems to study islet development, physiology, and pathology, and to develop therapies for insulin-dependent forms of diabetes — such as autoimmune or Type 1 diabetes.

Diabetes is a very complex disease, and our goal is to enable insulin independence. In order to do that, we need to replace the part of the body that is missing or deficient, just as you would replace parts of your car when you have a mechanical problem. We feel that we can make the tissue that is problematic in insulin-dependent diabetics — which is the pancreatic islets — in the laboratory and entrain it to match the rhythmic physiology of the body.

What inspired you to do the research?

I trained to be a scientist early on, but I was always of a split mind — I also wanted to do medicine. I applied for science and medicine combined degrees, and I was advised that I could make an advancement that would benefit not just the patients I met, but many patients around the world. And so, I literally sat down and thought about which diseases have a far-reaching impact. I asked myself, “What is a major issue that I could leave a footprint on?” After some thought, I realized that behind aging-related diseases, diabetes impacts hundreds of millions of people in our planet. We all know a friend, a relative, or a relative of a friend that has diabetes, so we are all fairly familiar with such a prevalent disease. My research is inspired by my desire to have a broad impact and diabetes is a disease where I think I can do that.

What are the biggest challenges you face as a scientist? Where do you see the greatest opportunities?

Every challenge is an opportunity, right? Currently, my biggest challenge is starting a new lab during the pandemic. It’s sort of like starting a new business, so there are some very down-to-earth logistical challenges — like supply chain issues or staffing. It can also be challenging to find time with family and cultivate the different aspects of yourself that keep you centered.

In terms of opportunities, I am trying to explore certain research areas where there hasn’t been as much progress. For example, at the intersection of cell development and circadian rhythms, there hasn’t been a lot of focus on how one influences the other. I see that as untapped potential, where we could bridge what we have already learned. If we are able to crack how having a rhythmic physiology helps cells become functionally specialized or “mature” for instance, then we can make better replacement tissues for patients — there’s a tremendous payoff. Venturing in that direction is a great opportunity.



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