The focus of our lab is the regulation of the Apaf-1 apoptosome by phosphorylation, ubiquitination, and free magnesium ions. The disassembly of mammalian cells by apoptosis generally depends on the oligomerization of the Apaf-1: caspase-9 apoptosome in the cytoplasm, which is evoked by the release of cytochrome c from mitochondria. Cellular inhibitor of apoptosis proteins antagonize Apaf-1 apoptosome activation by an unknown mechanism, which is being elucidated using purified proteins in vitro and in mammalian cells. Free magnesium ions cooperatively inhibit apoptosome assembly by competing with cytochrome c for Apaf-1. Raising intracellular free magnesium in mammalian cells inhibits the induction of apoptosis and activation of caspases-9 and -3. Novel compounds that either potentiate or antagonize apoptosome assembly are being tested to devise new chemotherapeutic approaches for either up or down regulating apoptosis.
Dr. Jeffrey Smith is a Professor in the Department of Pharmacology. He received his B.S. degree from Illinois State University in Normal, IL in 1967 in Biology and Chemistry. He went on to receive his Ph.D. degree from the University of Colorado Medical School in Denver in 1972 in Biochemistry. Dr. Smith moved to Ithaca, NY at Cornell University where he did postdoctoral training in Biochemistry until 1977; he continued his postdoctoral studies at the Imperial Cancer Research Fund in London, UK until 1978 in Cell biology. Dr. Smith joined the UAB faculty in 1980.