David M. Hockenbery

Members of Dr. Hockenbery's laboratory study the genetic and biochemical mechanisms of programmed cell death, or apoptosis, in a variety of experimental systems. Normal cell death occurring during development and following terminal differentiation has typical morphologic and biochemical features collectively termed apoptosis. The precise control of these events is obviously of great importance to the organism and many model systems have demonstrated the requirement for active RNA and protein synthesis for cell death to proceed, suggesting an internally programmed process. One regulator of this process is the bcl-2 oncogene, which blocks apoptosis in vitro and in vivo and appears to normally control the timing of cell death in many cell lineages. The following projects are currently active in the lab:

a. Investigation of the mitochondrial functions of the Bcl-2 family of apoptotic regulatory proteins. Recent efforts have led to the discovery of novel small molecules that inhibit Bcl-2 and related proteins.

b. Structure-function analysis of Bcl-xL homodimers, with recent demonstration of x-ray crystal structure of 3D domain swapped dimers.

c. Analysis of mitochondrial proteomics and mitochondrial assembly in apoptosis, with a focus on the effects of Hsp90 inhibitors on mitochondrial protein turnover.

d. Investigation of the role of the c-myc transcription factor in bioenergetic regulation in different cell contexts, including cell growth and division, neoplastic transformation and apoptosis.

e. Analysis of cell signaling and transcriptional responses to nutrient excess, in particular glucose sensing mechanisms employed in cells susceptible to neoplastic transformation.