David M. Hockenbery

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Fred Hutchinson Cancer Research Center
Professional Headshot of David M. Hockenbery

Mailing Address

Fred Hutchinson Cancer Research Center
1100 Fairview Avenue N., D2-190
P.O. Box 19024
Seattle, Washington 98109-1024
United States

Contact Information

Phone: (206) 667-4611
Fax: (206) 667-6519
dhockenb@fhcrc.org
http://www.fhcrc.org/science/labs/hockenbery

Qualifications

M.D., Washington University, 1982.
B.S., University of Rochester, 1978.

Expertise and Research Interests

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.

Keywords

COS Keywords:

Apoptosis, Biochemistry, Cell Cycle, Cell Differentiation, Genetics.

Additional Terms:

Apoptosis, Mitochondria.

Memberships

Biophysical Society
Mitochondria Research Society

Honors and Awards

2002, Member, American Society of Clinical Investigation
1991-1997, Scholar Award, Lucille P. Markey

Previous Positions

-2004, Member, Fred Hutchinson Cancer Research Center, Clinical Research and Human Biology
-2005, Professor, University of Washington, School of Medicine, Medicine, Gastroenterology

Publications

  • Morrish F (2006) Thyroid hormone receptor isoforms localize to cardiac mitochondrial matrix with potential for binding of receptor elements to mtDNA, MItochondrion, 6, 143-148
  • O'Neill JW, Manion MK (2006) BCL-XL dimerization by three-dimensional domain swapping, Journal of Molecular Biology, 356, 367-381
  • Wang H (2005) Preclinical pharmacology of 2-methoxyantimycin A compounds as novel antitumor agents, Cancer Chemother Pharmacol, 56, 291-298
  • Ho HK, Hu ZH, Tzung SP, Hockenbery DM, Fausto N, Nelson SD, Bruschi SA (Jan 2005) BCL-xL overexpression effectively protects against tetrafluoroethylcysteine-induced intramitochondrial damage and cell death, Biochemical Pharmacology, 69 (1), 147-57
  • O'Neill J, Manion M, Schwartz P, Hockenbery DM (Dec 2004) Promises and challenges of targeting Bcl-2 anti-apoptotic proteins for cancer therapy, Biochimica Et Biophysica Acta, 1705 (1), 43-51
  • Perry ME, Dang CV, Hockenbery D, Moll U ( Oct 2004) Highlights of the National Cancer Institute Workshop on mitochondrial function and cancer, , , 7640-4 pages
  • Hockenbery D (Apr 2004) Breaking down tumor defenses, Chemistry & Biology, 11 (4), 417-8
  • Lesnikov VA, Lesnikova MP, Shulman HM, Wilson HM, Hockenbery DM, Kocher M, Pierpaoli W, Deeg HJ (Mar 2004) Prevention of Fas-mediated hepatic failure by transferrin, Laboratory Investigation; a Journal of Technical Methods and Pathology, 84 (3), 342-52
  • Erxleben HA, Manion MK, Hockenbery DM, Scampavia L, Ruzicka J (Mar 2004) A novel approach for monitoring extracellular acidification rates: based on bead injection spectrophotometry and the lab-on-valve system, The Analyst, 129 (3), 205-12
  • Manion MK, O'Neill JW, Giedt CD, Kim KM, Zhang KY, Hockenbery DM (Jan 2004) Bcl-XL mutations suppress cellular sensitivity to antimycin A, The Journal of Biological Chemistry, 279 (3), 2159-65
  • O'Neill JW, Hockenbery DM (Aug 2003) Bcl-2-related proteins as drug targets, Current Medicinal Chemistry, 10 (16), 1553-62
  • Haughn L, Hawley RG, Morrison DK, von Boehmer H, Hockenbery DM (Jul 2003) BCL-2 and BCL-XL restrict lineage choice during hematopoietic differentiation, The Journal of Biological Chemistry, 278 (27), 25158-65
  • Hockenbery DM (Feb 2003) Nailing down a link between tuberin and renal cysts, The American Journal of Pathology, 162 (2), 369-71
  • Wright ME, Eng J, Sherman J, Hockenbery DM, Nelson PS, Galitski T, Aebersold R (2003) Identification of androgen-coregulated protein networks from the microsomes of human prostate cancer cells, Genome Biology, 5 (1), R4
  • Morrish F, Giedt C, Hockenbery D (Jan 2003) c-MYC apoptotic function is mediated by NRF-1 target genes, Genes & Development, 17 (2), 240-55
  • Manion MK, Hockenbery DM (Jul-Aug 2003) Targeting BCL-2-related proteins in cancer therapy, Cancer Biology & Therapy, 2 (4 Suppl 1), S105-14
  • Morrish F, Hockenbery D (Jan-Feb 2003) Myc's mastery of mitochondrial mischief, Cell Cycle (georgetown, Tex.), 2 (1), 11-3
  • Seewaldt VL, Mrozek K, Sigle R, Dietze EC, Heine K, Hockenbery DM, Hobbs KB, Caldwell LE, Suppression of p53 function in normal human mammary epithelial cells increases sensitivity to extracellular matrix-induced apoptosis, Journal of Cell Biology, 155(3), 471-486, 29 Oct 2001
  • Kim KM, Giedt CD, Basanez G, O'Neill JW, Hill JJ, Han YH, Tzung SP, Zimmerberg J, Hockenbery DM, Zhang KY, Biophysical characterization of recombinant human Bcl-2 and its interactions with an inhibitory ligand, antimycin A, Biochemistry, 40(16), 4911-22, 2001 Abstract
  • Tzung SP, Kim KM, Basanez G, Giedt CD, Simon J, Zimmerberg J, Zhang KY, Hockenbery DM, Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3, Nature Cell Biology, 3(2), 183-91, February 2001 Abstract
  • Wright ME, Han DK, Hockenbery DM, Caspase-3 and inhibitor of apoptosis protein(s) interactions in Saccharomyces cerevisiae and mammalian cells, Febs Letters, 481(1), 13-8, September 2000 Abstract
  • Welters CF, Piersma FE, Hockenbery DM, Heineman E, The role of apoptosis during intestinal adaptation after small bowel resection, Journal of Pediatric Surgery, 35(1), 20-4, Jan 2000 Abstract
  • Mostafapour SP, Hockenbery DM, Rubel EW, Life and death in otolaryngology: mechanisms of apoptosis and its role in the pathology and treatment of disease., Archives of Otolaryngology -- Head and Neck Surgery, 125(7), 729-37, July 1999 Abstract
  • Wright ME, Han DK, Carter L, Fields S, Schwartz SM, Hockenbery DM, Caspase-3 inhibits growth in Saccharomyces cerevisiae without causing cell death, Febs Letters, 446(1), 9-14, March 1999 Abstract
  • Knowlton K, Mancini M, Creason S, Morales C, Hockenbery D, Anderson B O, Bcl-2 slows in vitro breast cancer growth despite its antiapoptotic effect., Journal of Surgical Research, 76(1), 22-6, April 1998 Abstract
  • Mancini M, Sedghinasab M, Knowlton K, Tam A, Hockenbery D, Anderson B O, Flow cytometric measurement of mitochondrial mass and function: a novel method for assessing chemoresistance., Annals of Surgical Oncology, 5(3), 287-95, April 1998 Abstract
  • Camilleri-Broet S, Vanderwerff H, Caldwell E, Hockenbery D, Distinct alterations in mitochondrial mass and function characterize different models of apoptosis., Experimental Cell Research, 239(2), 277-92, 15 Mar 1998 Abstract
  • Mancini M, Anderson B O, Caldwell E, Sedghinasab M, Paty P B, Hockenbery D M, Mitochondrial proliferation and paradoxical membrane depolarization during terminal differentiation and apoptosis in a human colon carcinoma cell line., Journal of Cell Biology, 138(2), 449-69, 28 Jul 1997 Abstract
  • Tzung S P, Fausto N, Hockenbery D M, Expression of Bcl-2 family during liver regeneration and identification of Bcl-x as a delayed early response gene., American Journal of Pathology, 150(6), 1985-95, June 1997 Abstract
  • Robertson K A, Hill D P, Xu Y, Liu L, Van Epps S, Hockenbery D M, Park J R, Wilson T M, Kelley M R, Down-regulation of apurinic/apyrimidinic endonuclease expression is associated with the induction of apoptosis in differentiating myeloid leukemia cells., Cell Growth and Differentiation, 8(4), 443-9, April 1997 Abstract
  • Hirose K, Hockenbery D M, Rubel E W, Reactive oxygen species in chick hair cells after gentamicin exposure in vitro., Hearing Research, 104(1-2), 1-14, February 1997 Abstract
  • Park J R, Hockenbery D M, BCL-2, a novel regulator of apoptosis., Journal of Cellular Biochemistry, 60(1), 12-7, January 1996 Abstract
  • Hong D S, Beckham C, Huss R, Lee J W, Hockenbery D, Ledbetter J A, Deeg H J, Major histocompatibility complex class II-mediated inhibition of hematopoiesis in long-term marrow cultures involves apoptosis and is prevented by c-kit ligand [see comments], Blood, 86(9), 3341-52, 1 Nov 1995 Abstract
  • Park J R, Bernstein I D, Hockenbery D M, Primitive human hematopoietic precursors express Bcl-x but not Bcl-2., Blood, 86(3), 868-76, 1 Aug 1995 Abstract
  • Hockenbery D M, bcl-2, a novel regulator of cell death., Bioessays, 17(7), 631-8, July 1995 Abstract
  • Hockenbery D, Defining apoptosis [comment] [see comments], American Journal of Pathology, 146(1), 16-9, January 1995 Abstract
  • Park J R, Robertson K, Hickstein D D, Tsai S, Hockenbery D M, Collins S J, Dysregulated bcl-2 expression inhibits apoptosis but not differentiation of retinoic acid-induced HL-60 granulocytes., Blood, 84(2), 440-5, 15 Jul 1994 Abstract
  • Hockenbery D M, bcl-2 in cancer, development and apoptosis., Journal of Cell science. Supplement, 18, 51-5, 1994 Abstract
  • Hockenbery D M, Oltvai Z N, Yin X M, Milliman C L, Korsmeyer S J, Bcl-2 functions in an antioxidant pathway to prevent apoptosis., Cell, 75(2), 241-51, 22 Oct 1993 Abstract
  • Walton M I, Whysong D, O'Connor P M, Hockenbery D, Korsmeyer S J, Kohn K W, Constitutive expression of human Bcl-2 modulates nitrogen mustard and camptothecin induced apoptosis., Cancer Research, 53(8), 1853-61, 15 Apr 1993 Abstract
  • Hockenbery D M, The bcl-2 oncogene and apoptosis., Seminars In Immunology, 4(6), 413-20, December 1992 Abstract
  • Rao L, Debbas M, Sabbatini P, Hockenbery D, Korsmeyer S, White E, The adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins [published erratum appears in Proc Natl Acad Sci U S A 1992 Oct 15;89(20):9974], Proceedings of the National Academy of Sciences (USA), 89(16), 7742-6, 15 Aug 1992 Abstract
  • Sentman C L, Shutter J R, Hockenbery D, Kanagawa O, Korsmeyer S J, bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes., Cell, 67(5), 879-88, 29 Nov 1991 Abstract
  • Nunez G, Hockenbery D, McDonnell T J, Sorensen C M, Korsmeyer S J, Bcl-2 maintains B cell memory., Nature, 353(6339), 71-3, 5 Sep 1991 Abstract
  • Hockenbery D M, Zutter M, Hickey W, Nahm M, Korsmeyer S J, BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death., Proceedings of the National Academy of Sciences (USA), 88(16), 6961-5, 15 Aug 1991 Abstract
  • Zutter M, Hockenbery D, Silverman G A, Korsmeyer S J, Immunolocalization of the Bcl-2 protein within hematopoietic neoplasms., Blood, 78(4), 1062-8, 15 Aug 1991 Abstract
  • Hockenbery D, Nunez G, Milliman C, Schreiber R D, Korsmeyer S J, Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death., Nature, 348(6299), 334-6, 22 Nov 1990 Abstract
  • Nunez G, London L, Hockenbery D, Alexander M, McKearn J P, Korsmeyer S J, Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines., Journal of Immunology, 144(9), 3602-10, 1 May 1990 Abstract
  • Korsmeyer S J, McDonnell T J, Nunez G, Hockenbery D, Young R, Bcl-2: B cell life, death and neoplasia., Current Topics In Microbiology and Immunology, 166, 203-7, 1990 Abstract

Profile Details

Last Updated: 8/29/2006

COS Expertise ID #135194
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