Research Abstract

Dr.Glimcher is widely considered to be a world leader in understanding the transcriptional regulation of the cellular differentiation pathways in lymphocytes. She has made seminal discoveries of key transcription factors that drive lineage commitment and activation in the immune system, including the c-Maf and T-bet transcription factors, which regulate a variety of adaptive and innate immune functions in T lymphocytes. In revolutionary work, Dr. Glimcher’s group discovered the first TH1-specific transcription factor, T-bet and demonstrated that this single factor is a master regulator of both IFN-gamma gene expression and the TH1 phenotype. This work overturned the paradigm in the field of cellular immunology that differentiated TH cells are deviated irrevocably in one way or another since T-bet single-handedly could control this critical checkpoint at all stages of differentiation with its attendant therapeutic implications that T cell fate can be directly manipulated. Her laboratory exploited this discovery to create the first mouse model for spontaneous asthma accompanied by chronic airway remodeling, pathognomonic of human asthma, and showed that polymorphisms in the human T-bet gene associate with this disease. She further identified a critical function for T-bet in ulcerative colitis that progresses to colorectal cancer. She also discovered XBP1, the first transcription factor shown to be required for plasma cell differentiation and the mammalian Endoplasmic Reticulum Stress Response. She demonstrated a link between ER stress and proinflammatory/autoimmune diseases in intestinal epithelial cells and in macrophages. Most recently she discovered a key role for XBP1 in both tumor cells and in host immune responses, translating her basic discoveries in the control of immune cell differentiation into a new approach to cancer immunotherapy.