Dr. Arvan received his undergraduate degree from Cornell University followed by a medical degree as well as a doctorate in cell biology from the Yale University School of Medicine. He then pursued his residency and fellowship in endocrinology at Yale. He spent eight years on the faculty at Harvard University working at what is now the Beth Israel-Deaconess Medical Center, followed by seven years on the faculty of Albert Einstein College of Medicine in New York. In 2003, he moved to his current position as Chief of the Division of Metabolism, Endocrinology, and Diabetes at the University of Michigan. In 2006, after two years as interim director, he became director of the Comprehensive Diabetes Center at the University of Michigan.
Dr. Arvan's goal is to identify cellular factors and exogenous compounds that allow for beta cell survival and even expansion in the face of secretory pathway stress. This is accomplished by a combination of molecular biological and cell biological approaches that concentrate in animal models of diabetes, isolated pancreatic islets, and pancreatic beta cell lines. Dr. Arvan and his team intend to develop new molecular biological therapies, and small-molecule drug therapies, to allow sufficient insulin production to prevent, or at least limit the severity, of both type 1A and type 1B diabetes. The areas that they are focusing on include:
Examine pancreatic insulin content in live animals during onset and progression of type 1A diabetes and type 1B diabetes
Their goal is to develop a sophisticated system to measure the effectiveness of new treatments for type 1 diabetes. An NOD mouse model expressing human insulin and proportionate production of a green-fluorescent C-peptide has just completed construction. They will use fluorescence imaging in NOD females to examine the extent to which distinct therapies preserve pancreatic insulin content, and correlate these findings with direct metabolic studies of the animals. Their second model involves animals co-expressing the misfolded mutant Akita proinsulin that causes autosomal dominant type 1B diabetes. Dr. Arvan and his team will follow over time (age) the insulin content contributed by the nonmutant (fluorescent) proinsulin in these models. (Amazingly, in Akita animals, normal or even supranormal beta cell number and insulin content may exist during neonatal life — despite expression of the same misfolded mutant proinsulin.)
Small molecules that rescue bystander insulin secretion in the presence of misfolded proinsulins
Their goal is to complete the screening of a library of compounds that proinsulin to move successfully through the secretory pathway and become secreted as normal insulin, even in cells with secretory pathway stress. Lead compounds have been identified, and now key structure-function relationships in these compounds are needed to understand more about drug-target interaction. Such drugs, once developed into proper pharmaceuticals, could potentially be used to increase insulin production from those beta cells (and islets, animals, and humans) in type 1B and type 1A diabetes.
Degradation of misfolded proinsulin in pancreatic beta cells
Their goal is to determine whether degradation of misfolded proinsulin in pancreatic beta cells is a key to cell survival. Different misfolding mutants with different efficiency of degradation will be examing for their ability to kill beta cells. They wish to screen for compounds that promote misfolded proinsulin degradation, which could allow for enhanced insulin production from the remaining cohort of unaffected (pro)insulin molecules.
Regulatory T-cells promoting an environment of beta cell survival
With other members of the Brehm Coalition (such as Jeffrey Bluestone), Dr. Arvan and his team's goal is to determine whether cell therapy with Tregs could rescue pancreatic insulin production in non-autoimmune type 1B diabetes. If so, cell therapy with T-regs — by generating local factors that favor beta cell survival — could have enormous metabolic implications for diabetes of all forms.
Dr. Arvan is a past recipient of a PEW Foundation scholarship in the biomedical sciences, a Wellcome Visiting Professorship in the basic medical sciences and the winner of the R.R. Bensley award from the American Association of Anatomists. He has served as a reviewer for 15 specialty journals and is a former editorial board member of the Journal of Biological Chemistry and the American Journal of Physiology: Endocrinology and Metabolism. His is currently associate editor of the American Journal of Pathology. In 2003, Dr. Arvan established clinical practice in Michigan and was named one of Hour Detroit magazine’s “2006 and 2007 Top Docs”.
“It is one of the thrills of my life to help Bill Brehm develop a unique paradigm for collaborative science committed to discovery of new knowledge and delivery of new therapies for type 1 diabetes. This is a razor sharp group of scientists who bring to the table both an understanding of the fundamental gaps in our knowledge, and practical know-how of getting things done. What is so exciting here is that the roll-up-our-sleeves style of these investigators, working together, allows the group to reach farther than any one of us alone could ever do. The seriousness of intent, coupled with exceptional expertise, gives this group special opportunities for accomplishment that are both invigorating and inspiring. The University of Michigan has been nothing but supportive of my efforts in helping this mission as we partner the Coalition activities with the launching and development of the new Brehm Center for Type 1 Diabetes Research and Analysis on the U-M campus.”