David M. Hockenbery
M.D., Washington University, 1982.
B.S., University of Rochester, 1978.
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.
American Association for the Advancement of Science
American Society for Cell Biology
American Society of Clinical Investigation
Mitochondria Research Society
Honors and Awards
2002, Member, American Society of Clinical Investigation
1991-1997, Scholar Award, Lucille P. Markey
1999-2004, Associate Member, Fred Hutchinson Cancer Research Center, Clinical Research and Human Biology
1998-2005, Associate Professor, University of Washington, School of Medicine, Medicine, Gastroenterology
1992-1998, Assistant Member, Fred Hutchinson Cancer Research Center, Clinical Research Division
Gastrointestinal and hepatic complications. Thomas’ Hematopoietic Cell Transplantation.. In Press.
Disruption of fnip1 reveals a metabolic checkpoint controlling B lymphocyte development.. Immunity. 36(5):769-81.. 2012.
Reduced cytochrome C is an essential regulator of sustained insulin secretion by pancreatic islets.. The Journal of biological chemistry. 286(20):17422-34.. 2011.
Investigating neoplastic progression of ulcerative colitis with label-free comparative proteomics.. Journal of proteome research. 10(1):200-9.. 2011.
Blood and gastric FOXP3+ T cells are not decreased in human gastric graft-versus-host disease.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 17(4):486-96.. 2011.
Myc-dependent mitochondrial generation of acetyl-CoA contributes to fatty acid biosynthesis and histone acetylation during cell cycle entry.. The Journal of biological chemistry. 285(47):36267-74.. 2010.
Induction of the Warburg effect by Kaposi's sarcoma herpesvirus is required for the maintenance of latently infected endothelial cells.. Proceedings of the National Academy of Sciences of the United States of America. 107(23):10696-701.. 2010.
Targeting mitochondria for cancer therapy.. Environmental and molecular mutagenesis. 51(5):476-89.. 2010.
Activation of NF-kappaB by palmitate in endothelial cells: a key role for NADPH oxidase-derived superoxide in response to TLR4 activation.. Arteriosclerosis, thrombosis, and vascular biology. 29(9):1370-5.. 2009.
c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry.. Oncogene. 28(27):2485-91.. 2009.
Bcl-2 family proteins as regulators of oxidative stress.. Seminars in cancer biology. 19(1):42-9.. 2009.
Identification of genes with abnormal expression changes in acute myeloid leukemia.. Genes, chromosomes & cancer. 47(1):8-20.. 2008.
Differential responses of FLIPLong and FLIPShort-overexpressing human myeloid leukemia cells to TNF-alpha and TRAIL-initiated apoptotic signals.. Experimental hematology. 36(12):1660-72.. 2008.
The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry.. Cell cycle (Georgetown, Tex.). 7(8):1054-66.. 2008.