James Verbsky, MD PhD
Pediatrics - Division of Rheumatology, Microbiology and Molecular Genetics
Medical College of Wisconsin
Research Focus: Immune regulation, T regulatory cells, role of IL-2 and IL-10 in immune regulation, mechanisms of suppression of immune responses by T regulatory cells
MD PhD: Washington University School of Medicine (2000) Immunology
My research interests focus on immune regulation, and are based on observations of patients with genetic deficiencies of genes important in immune regulation with a focus on T regulatory cells. Previous work in my laboratory demonstrated that that two types of human T regulatory cells exhibited novel mechanisms of suppression that involve cytotoxicity mediated by the granzyme/perforin pathway. These studies shifted the dogma at the time of the mechanism of suppression by T regulatory cells. During this time I also studied two patients with IPEX (Inflammatory Polyendocrinopathy, enteropathy, X-linked) and determined that IPEX can be caused by a genetic defect in CD25 expression, the high affinity IL-2 receptor.
One of the most interesting observations of CD25 deficiency was the complete absence of IL-10 production from stimulated CD4 cells, as well as the severe inflammatory bowel disease in this patient. I have continued to study the requirements for IL-10 production in both humans and mice, and have novel genetic models to define the requirements for IL-10 production, such as CD25 and IL-10 deficient mice, and IL-10 reporter mice. This research application expands on this research interest. Starting with a patient with severe inflammatory bowel disease due to a novel genetic deficiency in the X linked inhibitor of apoptosis gene, we have begun to ask whether the reason for his disease is because of defective IL-10 expression. We were able to show this in vitro, and the purpose of this grant is to model this disease and examine whether XIAP is required for IL-10 production in vivo. We anticipate that the findings of this grant will provide a clearer understanding of the role of IL-10 in preventing inflammatory bowel disease.
Dr. James Verbsky
Children's Hospital of Wisconsin
Children's Corporate Center, Suite C465
PO Box 1997
9000 W. Wisconsin Avenue
Milwaukee, WI 53201-1997