The featured speaker for The Roy J. Carver Department of Biochemistry, Biophysics, and Molecular Biology (BBMB) Fall 2017 Seminar Series for TODAY, Thursday, November 2nd, is Dr. Miles Pufall, from the Department of Biochemistry – University of Iowa. His seminar topic, “Interrupting Double Negative Feedback Loops to Increase Glucocorticoid Potency in Leukemia Treatment”, will be presented at 4:10 p.m. in Room 1414 - Molecular Biology Building.
Please join us for refreshments Thursday afternoon, November 2nd, at 3:45 p.m. in the MBB Atrium. Dr. Dipali Sashital is the host for Dr. Pufall’s visit.
Abstract: The glucocorticoid receptor (GR) is expressed in every tissue of the body, yet has diverse roles in each, ranging from suppressing inflammation to inducing cell death. To determine the signals that impinge on GR, and how they change its structure and activity, we study their function lymphoid malignancies, specifically B-cell precursor acute lymphoblastic leukemia (B-ALL). Glucocorticoids are a critical component of combination chemotherapy, and are normally highly effective in treatment of B-ALL, but their use is hampered by resistance and life-threatening side-effects in patients. Upon binding to glucocorticoids GR translocates from the cytoplasm to the nucleus and directly regulates genes, and by taking a functional genomics approach, were able to identify genes and pathways, including the B-cell receptor pathway, that restrain GR function specifically in B-cells. By inhibiting components of these pathways, we can alter the modification of GR or its cofactors and increase glucocorticoid potency in B-ALL.
In the course of these studies we found a surprising new role for GR: regulating B-cell development. Our current model is that endogenous glucocorticoids (e.g. cortisol) have an influence on lymphoid specification and B-cell selection. This regulation is both direct, through repression of other developmental transcription factors, and indirect by altering the gene splicing.