School of Pharmacy

Rajindar Singh Sohal, PhD

Research Interest

The overarching objective of research in my laboratory is to understand causal mechanisms of aging. The focus is on the oxidative stress hypothesis of aging, utilizing both insect and mammalian model organisms. One line of research, performed in collaboration with Prof. W. C. Orr of Southern Methodist University, involves the development of transgenic fruit flies Drosophila melanogaster, overexpressing various antioxidative enzymes, notably Cu, Zn, and Mn superoxide dismutases, catalase, thioredoxin reductase, glutamate-cysteine ligase and glucose-6-phosphate dehydrogenase. An emerging trend in these studies is that the use of binary GAL4-UAS transgenic systems to target overexpression to specific tissue types can extend the life span. Biochemical and physiological studies of these and other flies include measurements of oxygen consumption at the organismal level (Sable Systems respirometry) and in isolated mitochondria (oxygraph measurements). Additionally, we use immunoblot analysis to detect oxidative damage, including protein carbonylation and modifications by 4-hydroxynonenal and malondialdehyde. We also perform flourimetric assays of mitochondrial hydrogen peroxide release, and spectrophotometric assays of antioxidative enzyme activities and mitochondrial aconitase activity (a sensitive target for oxidative inactivation during aging).

A second line of research, performed in collaboration with Prof. M. Forster of the University of North Texas - Health Sciences Center, examines the effects of caloric restriction on aging in mice and rats. A recent finding is that caloric restriction is not universally beneficial: it does not extend the life span of houseflies or of the DBA/2 strain of mice. Biochemical and physiological characterization of this strain, using methods described above for flies, is currently in progress. An additional project involves dietary supplementation with coenzyme Q, which is believed to have an antioxidative effect. We have found that supplementation leads to increased uptake of the compound, but it does not affect oxidative stress or longevity. High performance liquid chromatography (HPLC) is used in the lab to measure the amounts of oxidized and reduced glutathione, NAD(H), NADP(H), and protein mixed disulfides. These indices of oxidative stress and redox state are of major importance to the projects involving both rodents and flies.

Biography

Dr. Sohal received his B.Sc.H. and M.Sc. degrees from Punjab University (Chandigarh, India) and his Ph.D. in Zoology from Tulane University (New Orleans, LA). Before his arrival at USC in 2000, he was a University Distinguished Professor of Biological Sciences at Southern Methodist University (Dallas, Texas), Visiting Professor at Linkoping University (Sweden), Guest Professor at University of Dusseldorf (Germany), and Senior Scholar in the Department of Zoology, Cambridge University (UK). Dr. Sohal is currently Timothy M. Chan Professor of Pharmacology and Pharmaceutical Sciences.

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Research Support

Principal investigator of 4 RO1 grants from NIH

Selected Projects/Publications

Orr, W.C. and Sohal, R.S. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263: 1128-1130, 1994.

Sohal, R.S. and Weindruch, R. Oxidative stress, caloric restriction, and aging." Science 273(5271): 59-63, 1996.

Sohal, R.S., Mockett, R.J., and Orr, W.C. Mechanisms of aging: An appraisal of the oxidative stress hypothesis. Free Radical Biology & Medicine, 33: 575-586, 2002.