Research Interests
Apoptosis, Genotoxic Stress, Heat shock proteins, Cancer
Research in my laboratory focuses on the regulation of apoptotic cell death. Evidence indicates that apoptosis is vital for normal embryonic development and the maintenance of tissue homeostasis. Consequently, disturbances in apoptosis have been implicated in the onset of numerous pathological conditions, including autoimmune disorders, neurodegenerative disease, and cancer. Further, toxicity or carcinogenicity brought about by various environmental exposures appears to result at least partially from a dysregulation of apoptosis.
My research program is generally interested in understanding how chemical or physical damage to a cell causes the activation of cell death pathways. Of particular interest is how DNA damage caused by either anticancer drugs or environmental mutagens results in the engagement of the mitochondrial apoptotic pathway. In collaboration with an investigator on the Lawrence campus, we are also currently interested in understanding how inhibiting heat shock protein 90 function using small molecule inhibitors causes an antiproliferative response in malignant cells.
Our approach mostly employs mammalian cell culture and various biochemical and molecular techniques, including enzyme assays, Western blotting, measurement of mitochondrial function, recombinant protein expression and purification, high resolution imaging, transfections, and flow cytometry.
Robertson, J.D., Gogvadze, V., Zhivotovsky, B. and Orrenius, S. (2000) Distinct pathways for stimulation of cytochrome c release by etoposide. J. Biol. Chem. 275: 32438-32443.
Gogvadze, V., Robertson, J.D., Zhivotovsky, B. and Orrenius, S. (2001) Cytochrome c release occurs via Ca2+-dependent and Ca2+-independent mechanisms that are regulated by Bax. J. Biol. Chem. 276: 19066-19071.
Ott, M.*, Robertson, J.D.*, Gogvadze, V.*, Zhivotovsky, B. and Orrenius, S. (2002) Cytochrome c release involves a two-step process. Proc. Natl. Acad. Sci. U S A 99: 1259-1263. (*contributed equally to this work)
Robertson, J.D., Enoksson, M., Suomela, M., Zhivotovsky, B. and Orrenius, S. (2002) Caspase-2 acts upstream of mitochondria to promote cytochrome c release during etoposide-induced apoptosis. J. Biol. Chem. 277: 29803-29809.
Gogvadze, V., Robertson, J.D., Zhivotovsky, B. and Orrenius, S. (2004) Mitochondrial cytochrome c release may occur by volume-dependent mechanisms not involving permeability transition. Biochem. J. 378: 213-217.
Robertson, J.D., Gogvadze, V., Kropotov, A., Vakifahmetoglu, H., Zhivotovsky, B. and Orrenius, S. (2004) Processed caspase-2 can induce mitochondrial apoptosis independently of its enzymatic activity. EMBO Rep. 5: 643-648.
Enoksson, M., Robertson, J.D., Gogvadze, V., Bu, P., Kropotov, A., Zhivotovsky, B. and Orrenius, S. (2004) Caspase-2 permeabilizes the outer mitochondrial membrane and disrupts the binding of cytochrome c to anionic phospholipids. J. Biol. Chem. 279:49575-49578.
Franklin, E.E. and Robertson, J.D. (2007) Requirement of Apaf-1 for mitochondrial events and the cleavage or activation of all procaspases during genotoxic stress-induced apoptosis. Biochem. J. 405: 115-122.
Shawgo, M.E., Shelton, S.N. and Robertson, J.D. (2008) Caspase-mediated Bak activation and cytochrome C release during intrinsic apoptotic cell death in Jurkat cells. J. Biol. Chem. 283: 35532-35538.
Shelton, S.N., Shawgo, M.E. and Robertson, J.D. (2009) Cleavage of Bid by executioner caspases mediates feed forward amplification of mitochondrial outer membrane permeabilization during genotoxic stress-induced apoptosis in Jurkat cells. J. Biol. Chem. 284: 11246-11255.
John D. Robertson, Ph.D.
Assistant Professor
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
MS 1018
3901 Rainbow Boulevard
Kansas City, Kansas 66160
Office: (913) 588-0383
Fax: (913) 588-7501
Email: jrobertson3@kumc.edu
Updated 4/23/09
©
The University of Kansas Medical Center