Dr. Peter Arvan - Unraveling the Manufacturing Process

Peter Arvan, MD, PhD is the William K. and Delores S. Brehm Professor of Type 1 Diabetes Research, Professor of Internal Medicine, and Professor of Molecular and Integrative Physiology. For over the past 16 years, Dr. Arvan has served as Chief of the Division of Metabolism, Endocrinology & Diabetes (MEND). His research is focused on studying the secretory protein products from pancreatic beta cells and thyroid epithelial cells with the hope of developing new therapies that better treat diabetes and other endocrine diseases. Dr. Arvan received the 2017 Distinguished Faculty Lectureship Award in Biomedical Research, the highest honor bestowed by the Medical School upon a faculty member for research in the biomedical sciences.

Behind the Scenes with Dr. Peter Arvan

Dr. Peter Arvan

What is your research about?

All cells secrete proteins, but many cell types that control the secretion of important protein hormones are unbelievably specialized for this activity.

For example, the cells that make insulin make a ton of it! When a cell first makes a protein from its component amino acids, it is almost like making a piece of uncooked spaghetti that is initially generated as a linear rod. However, that’s not the shape of the final protein product. Using the pasta analogy, it might end up in the shape of a tortellini or gnocchi. So a cell making insulin might have to generate 6,000 of those pieces of pasta and turn them into properly-shaped tortellini all within a single second.

The other hormone-producing cell type that we are focused on is the thyroid epithelial cell, which has to make even more thyroglobulin, which is a bigger and more difficult-to-fold protein than insulin.

My research is about how these cells go about the bulk manufacturing process of making their major secretory protein products.

One of his recent studies, published in eLife, was featured in the articleHow Proinsulin Misfolding Is a Prelude to Type 2 Diabetes”.

Why is this area of research interesting to you?

As you might guess, when your body has to manufacture that many secretory proteins on such an incredible scale and in such a short period of time, things can go wrong. When that happens, it brings about hormone deficiency and the disease that goes with it. The most obvious situation is with a patient who inherits a single “missense” mutation in either insulin (in pancreatic beta cells) or thyroglobulin (in thyroid epithelial cells). Amazingly, in this case, just one amino acid change is enough to totally stop the protein in its tracks so that it is not secreted and therefore cannot fulfill its intended function. The fact that one minor change can have such a profound effect has always intrigued me.

What are a few conditions you are currently looking into?

With regards to pancreatic beta cells, we’ve been interested in patients with a syndrome called Mutant Insulin gene-induced Diabetes of Youth. Most of these unlucky patients with a protein folding problem develop diabetes before they are even one-year-old. But the problem can also happen in patients that do not have any mutation in the insulin gene — when patients become overweight, many have to make much more insulin to deal with that — and in some of these patients, because of protein misfolding, their pancreatic beta cells simply cannot keep up with that amount of insulin production. Those patients get type 2 diabetes, which is the world’s most common form of diabetes.

Additionally, in the thyroid, we have been studying patients that have a disease called Congenital Hypothyroidism with Mutant Thyroglobulin. At least 167 different mutations have been found to cause the disease which makes it a very complicated problem.  

What is the ultimate goal of your research? 

Our goal is to understand the bad consequences of secretory protein misfolding so that we can fix it. If our work is successful, it could cure people from this kind of disease, and that would be huge!

What are your clinical interests?

These days I’m not seeing new patients, however, over my past years of practice, I have long been interested in patients with diabetes and hypothyroidism. Interestingly, in many patients, the two diseases go together in the same person. I have also been interested in what we call “general endocrinology”. In other words, any endocrine patient that walks through the clinic door.

Also, I am very interested and engaged in our clinic and hospital-based practice operations. This includes strategizing ways to deliver the very best care to patients — how long they wait for an appointment, how quickly they check into an exam room, the quality of the medical decision making that they get from all of our clinical providers, and their personal satisfaction that their medical needs have been met in an efficient and happy way.  

Why did you decide to specialize in endocrinology?

My dad had type 1 diabetes and hypothyroidism, which was always a source of fascination. My mom had type 2 diabetes. I guess those things rubbed off on me.  

What accomplishment are you most proud of?

There is a lot that I am proud of here. We have transformed our endocrine division from a “mom-and-pop shop” into a modern full-service unit with more than 60 primary faculty members. We are one of the largest and strongest in the United States, including all areas of endocrinology, diabetes, obesity, endocrine oncology, and podiatry (which is a major clinical care need for diabetic patients).

From a mentoring standpoint, I am super proud of all the junior faculty who joined the MEND division under my watch and have gone on to develop robust careers. They are my living legacy.

From a discovery standpoint, I think our science contributions, particularly in recent years, have improved the general understanding of how important protein misfolding is in causing disease, which is not just limited to the endocrine system, but includes neurodegenerative diseases, aging, as well as diseases of other specialized organ systems.  

What advice would you give to someone who is considering specializing in endocrinology?

Everyone is different, but if you are looking for a place to follow your intellectual passion, this field and its logic about how the body works, can be incredibly rewarding. And clinically, I am impressed how a person can help quite a high fraction of the patients who come seeking help — and that is also emotionally rewarding.   

What gives you the most satisfaction in your job?

As division chief, I have the privilege of finding satisfaction in several different areas of my work. Just a few examples of where I take enormous pride is when our junior faculty get their first NIH grant, when I get a heartfelt thank you from a patient, and when one of my lab members comes into my office with an exciting result. There are a lot of ways to have a good day at work.

Is there a moment when you knew you had chosen the right career?

It was right after I got my first NIH grant — I was still an Assistant Professor — but I had the feeling “I can do this”, which is like the pride that a toddler takes when first learning to walk.  

Who has inspired you the most?

Wow, there are many people I have admired for all sorts of different reasons. The late Donald Steiner was one of my physician-scientist heroes and a friend. The late George Palade, Nobel Prize winner, was another of my science heroes and was a member of my thesis committee. The late Norman Fleischer taught by example about what it is to be an outstanding division chief. The late Roger Grekin similarly taught by example about what it is to be an authentic human being, who also just happens to be a really sharp endocrinologist. My own science advisor, David Castle, exhibits a contagious enthusiasm for knowledge that I have forever admired. Some of the people who have worked with me have been equally inspirational. The late Paul Kim was my former trainee and was responsible for much of my early scientific success before he developed a debilitating and ultimately lethal neurological disease. And a number of my current colleagues are super inspirational. I’ve been lucky.  

How do you balance your work and personal life?

I don’t want to pretend to be a role model because the balance that each person needs to be happy can fluctuate at different stages of life. One thing’s for sure — I have a very accomplished spouse as well as a rapidly-developing and impressive progeny. They are good to be around, and these days we spend a lot of time in the house talking about politics! This reminds all three of us that the world has many bigger and more stressful problems than our day jobs.  

What five words best describe you?

Human, striving, comic, academic, and dad.

More about Dr. Arvan…

You can learn more about his research work at Peter Arvan Lab Website and find all of his publications at Michigan Research Experts.

You can listen to him talk about what it’s like for people living with diabetes, the work that the MEND Division is doing in this area, and what still needs to be done. Watch the video.