Nepom Laboratory
Although we know that HLA genes are implicated in many autoimmune diseases, we do not yet understand the molecular mechanisms responsible for such genetic associations. Nor do we understand how to use this information to design better diagnostics, prognostics and therapeutics for clinical applications. In the Nepom Laboratory, we use a combined structural, genetic and functional approach to study the interaction between MHC molecules, peptides and T cell recognition, focusing on the HLA molecules associated with autoimmune disease. We would like to understand what the unique features are that lead to the expression and function of these molecules contributing to autoimmunity, and to gain some practical insight into opportunities to detect, modulate or block the specific molecular pathways in disease pathogenesis.
We explore a four-step model for development of autoimmune diseases, in which autoreactive T cells are selected in development, amplify in the periphery, activate in affected tissue, and escape from regulatory controls. Strategies to test this model include in vivo transgenic systems and ex vivo human systems, exploring the interactions between TCR avidity for the MHC-peptide complex, polymorphism of class II genes, and subsequent T cell activation and commitment.
We also use HLA genetics as predictive markers of disease susceptibility, and MHC tetramer analysis to stratify patients for clinical disease and response to therapy studies.
Laboratory Members
Gerald Nepom, MD, Director of BRI
Paul Bollyky, MD
Emily Burwell
Ivana Durinovic-Bello, PhD
John Gebe, PhD
Vivian Gersuk, PhD
Ben Falk
Tuan Nguyen
Nicole Pratt
Nathan Standifer, PhD
Rebecca Wu
Betty Yue