Research Interests
Apoptosis, DNA damage, toxicology
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 the genome leads to the activation of cell death pathways. Of particular interest is how DNA damage caused by either antineoplastic topoisomerase II inhibitors or environmental mutagens results in the engagement of the mitochondrial apoptotic pathway. This work is currently focused on understanding how caspase-2 contributes to this process and how cells made resistant to DNA-damaging agents due to an overexpression of bcl-2 or bcl-xL evade death.
Our approach employs both in vitro and in vivo experimental models, as well as various biochemical and molecular techniques, including enzyme assays, Western blotting, measurement of mitochondrial function, recombinant protein expression and purification, high resolution imaging, mammalian cell transfections, and flow cytometry.
Robertson, J.D., Starnes, J.W. and Kehrer J.P. (1997) Cosubstrates involved in the reduction of cytosolic glutathione disulfide in rat heart. Toxicology 124: 11-19.
Robertson, J.D., Datta, K., Biswal, S.S. and Kehrer, J.P. (1999) Heat-shock protein 70 antisense oligomers enhance proteasome inhibitor-induced apoptosis. Biochem. J. 344: 477-485.
Robertson, J.D. and Orrenius, S. (2000) Molecular mechanisms of apoptosis induced by cytotoxic chemicals. Crit. Rev. Toxicol. 30: 609-627.
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.
Samali, A., Robertson, J.D., Peterson, E., Manero, F., van Zeijl, L., Paul, C., Cotgreave, I.A., Arrigo, A-P. and Orrenius, S. (2001) Hsp27 protects mitochondria of thermotolerant cells against apoptotic stimuli. Cell Stress Chaperon. 6: 49-58.
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.
Robertson, J.D. and Orrenius, S. (2001) Biochemical signals that initiate apoptosis. In Comprehensive Toxicology, Volume XIV: Cellular and Molecular Toxicology, Vanden Heuvel, JP, Greenlee WF, Perdew GH, Mattes W, eds., pp. 443-462.
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., Fadeel, B., Zhivotovsky, B. and Orrenius, S. (2002) 'Centennial' Nobel conference on apoptosis and human disease. Cell Death Differ. 9: 468-475.
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.
Robertson, J.D., Zhivotovsky, B., Gogvadze, V. and Orrenius, S. (2003) Outer mitochondrial membrane permeabilization: an open-and-shut case? Cell Death Differ. 10: 485-487.
Robertson, J.D., Orrenius, S. and Zhivotovsky, B. (2003) Mitochondria and oxidation in the regulation of cell death. In When Cells Die II: A Comprehensive Evaluation of Apoptosis and Programmed Cell Death, Lockshin RA, Zakeri, Z, eds., pp. 381-401.
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. doi10.1074/jbc.C400374200
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 08/12/2005
©
The University of Kansas Medical Center