Scott H. Kaufmann M. D., Ph.D
Professor of Pharmacology and Medicine
Division of Oncology Research
Mayo Clinic
Title: Apoptotic BAK Activation: A Look at the Heart of a (Cell) Killer
Abstract: Both targeted and conventional anticancer drugs kill susceptible neoplastic cells by inducing apoptosis. Most of these agents trigger the mitochondrial apoptotic pathway, which is regulated by interactions between various members of the BCL2 family of proteins. Two BCL2 family members, BAX and BAK play a critical role in this pathway by triggering mitochondrial outer membrane permeabilization (MOMP). While BAX predominates in epithelial tissues, BAK is particularly abundant in normal leukocytes, leukemia cell lines, and clinical leukemia specimens. Building on our earlier studies demonstrating that BAK activation can be initiated by two distinct processes, transient binding of so-called BH3-only BCL2 family members in response to certain stimuli or concentration-dependent autoactivation, we are attempting to understand how BAK causes MOMP. Our recent studies have focused on a domain in the C-terminal half of BAK that is capable of binding MOM lipids and permeabilizing membranes, providing new insight into a critical step in anticancer drug-induced killing.
Bio: Dr. Kaufmann received M.D. and Ph.D. degrees from the Johns Hopkins University (JHU) School of Medicine. Since completing his residency in Internal Medicine and fellowship in Medical Oncology, he has conducted research and cared for acute leukemia patients at JHU and, since 1994, Mayo Clinic. The overall goal of his research program is to improve the therapy of neoplastic diseases through better understanding of cell death processes – particularly apoptosis – triggered by targeted antineoplastic agents.
