Yi-Guang Chen, PhD
Microbiology and Immunology
Medical College of Wisconsin
Research Focus: Immunogenetics of type 1 diabetes
PhD, University of Rochester (2002), Pathology and Laboratory Medicine
Type 1 diabetes (T1D) results from T cell mediated destruction of insulin producing pancreatic β-cells. Although T1D is most frequently diagnosed in children and young adults, it is a life-long disease requiring daily injections or infusions of exogenous insulin to maintain glucose homeostasis. Furthermore, many T1D patients develop diabetic complications later in life significantly threatening the quality of their lives. Unfortunately, the incidence of T1D has been increasing worldwide in the past decades. Studies conducted in both rodent models and humans indicate that genetic susceptibility significantly contributes to T1D development. Human genome wide association studies (GWAS) have identified more than 50 loci significantly linked to T1D. However, our knowledge of the underlying genes within the mapped GWAS regions and their pathogenic roles in T1D is incomplete. The focus of our research program is to further understand the genetic basis of T1D with the following three main goals. (1) To identify T1D susceptibility genes and mechanistically study their disease modulating functions, (2) To evaluate the potential of pharmaceutical targeting of T1D susceptibility genes and the pathways in which they are involved for disease prevention and reversal, and (3) To determine if T1D susceptibility genes also modulate the responses to clinically relevant therapeutic agents. The NOD mouse represents one of the best rodent models for T1D research. NOD mice develop spontaneous T1D with characteristics similar to the human disease. Our current effort is to genetically modify genes within the human T1D susceptibility loci identified by GWAS in NOD mice and functionally evaluate their roles in diabetes development. These genetically modified NOD mice also allow us to study how T1D susceptibility genes contribute to diabetes development at both the molecular and cellular levels.
Figure 1. Islet infiltration of leukocytes that destroy pancreatic β-cells in NOD mice. (A) A healthy islet without leukocyte infiltration. (B-D) Islets with various levels of leukocyte infiltration (insulitis).