Timothy “Lain” Hostelley, Ph.D.

Hostelly, Laine

Molecular Medicine

Area of Doctoral Study: Molecular Medicine

Undergraduate Institute: Lycoming College

Research Advisor: Norann Zaghloul, Ph.D.

Description of Research

My research focuses on the differential susceptibility to type 2 diabetes mellitus (T2DM) in the obese, as obesity is one of the greatest risk factors towards the development of T2DM. The rapidly increasing rates of obesity among children and adults in the United States presents a need for understanding the mechanisms of susceptibility to T2DM. Rare obesity disorders, such as the obesity ciliopathies Alström Syndrome (Alms) and Bardet-Biedl Syndrome (BBS), are a valuable tool for investigating these mechanisms. Both Alms and BBS are characterized by highly penetrant, early onset obesity; however, they have strikingly different rates of T2DM. The rate of T2DM is 70% by age 20 among Alms patients, and as low as 2-6% among BBS patients. Previous work in the lab has identified β-cell dysfunction in Alms, and protection against β-cell and glucose homeostasis defects in BBS, as a possible mechanism for the different rates of T2DM between these disorders. However, their exact function in β-cells remains unknown. Through the use of whole transcriptome sequencing, we identified several exocrine pancreas enzymes that likely have an effect on endocrine pancreas function and subsequent development, or lack thereof, of T2DM. These enzymes were found to be significantly downregulated in Alms and significantly upregulated in BBS. Using the zebrafish animal model, as well as cultured β-cells, my work aims to define the role that the exocrine pancreas plays in the development of, and production of insulin by, the β-cell mass of the endocrine pancreas.