Novel Calcium Dependent Mechanisms of NF-kappaB Activation Regulate Lymphocyte Tolerance & Immunity

Thursday, May 31, 2018

2:00 PM-4:00 PM

BIOMED PhD Thesis Defense

Title:
Novel Calcium Dependent Mechanisms of NF-kappaB Activation Regulate Lymphocyte Tolerance and Immunity

Speaker:
Corbett T. Berry, MD/PhD Candidate, School of Biomedical Engineering, Science and Health Systems

Advisors:
Bruce D. Freedman, VMD, PhD, Associate Professor, School of Veterinary Medicine, University of Pennsylvania

Uri Hershberg, PhD, Associate Professor, School of Biomedical Engineering, Science and Health Systems, Drexel University

Abstract:
Antigen induced Ca2+ signals regulate the development of immunity and tolerance. These signals are generated when antigen binds cognate receptors on lymphocytes and triggers Ca2+ entry into the cytoplasm. Indeed, patients with functional defects in the ER transmembrane Ca2+-sensing STIM proteins, or the STIM-activated Ca2+ entry channel Orai, exhibit devastating immunodeficiency and autoimmunity.

This immune phenotype occurs as a result of dysfunctional lymphocyte development and function principally through aberrant activation of Ca2+ dependent transcription factors including NFAT and NF-kB. While the role of Ca2+ signaling in NFAT activation and signaling is well established, a wide appreciation and mechanistic understanding of how Ca2+ signals also shape the activation and specificity of NF-kB dependent gene expression is incomplete.

In these studies, we establish that STIM/Orai dependent Ca2+ entry regulates multiple checkpoints in NF-kB signaling, but also NF-kB independent pathways to regulate lymphocyte survival, proliferation, and differentiation.

Contact Information

Ken Barbee
215-895-1335
barbee@drexel.edu