Faculty

Jeffrey Friedman 
Assistant Professor
Department of Molecular and Experimental Medicine
TSRI - 2003

Education 
M.D. Stanford University, 1993

Ph.D. Stanford University, 1993

Awards & Activities 
Ellison Medical Foundation New Scholar in Aging

Research Focus 
Oxidative Stress as a Contributing Factor in Anemia and Aging
Our lab is interested in how cells respond to oxidative stress, and how alterations in that response can result in specific pathologies or affect aspects of "normal" aging. We currently focus upon two genes: superoxide dismutase 2 (sod2) and p66Shc. Sod2 is involved in detoxification of reactive oxygen produced in mitochondria, while p66Shc is a component of a signaling pathway that mediates cell death in response to oxidant stress. Lack of Sod2 results in severe mitochondrial dysfunction--when this deficiency is restricted to blood cells (in mice) the result is a hemolytic anemia that models the human disorder Sideroblastic anemia, in which iron accumulates in erythroid cells. Using proteomic and gene array approaches, we identify and study proteins/genes affected by oxidative damage and characterize the therapeutic mechanism of catalytic antioxidants in Sod2 deficient cells.

The p66shc project focuses upon characterization of a signaling pathway that acts like a rheostat in setting the level of sensitivity of a cell to oxidant stress. Indirect evidence places p66shc downstream from the tumor suppressor protein p53 and upstream of the forkhead transcription factor FOXO3a in a pathway that results in cell death upon oxidant stress. We are interested in identifying components of this signaling pathway using both direct biochemical techniques and indirect screens that depend upon alterations in sensitivity to oxidants. We are also interested in determining whether recently described mutant p53 proteins (that accelerate the rate of aging in mice) require p66 function.

Selected References 
Martin, F. M., Friedman, J.S. (2004). Aging Fast or Aging Slow: Through Shc Must You Go? Science SAGEKE, published online August 2004.

Friedman, J. S., Alpdogan, O., van den Brink, M. R., Liu, C., Hurwitz, D., Boyd, A., Kupper, T. S., and Burakoff, S. J. (2004a). Increasing T-cell age reduces effector activity but preserves proliferative capacity in a murine allogeneic major histocompatibility complex-mismatched bone marrow transplant model. Biol Blood Marrow Transplant 10, 448-460.

Friedman, J. S., Lopez, M. F., Fleming, M. D., Rivera, A., Martin, F. M., Welsh, M. L., Boyd, A. S., Doctrow, S. R., and Burakoff, S. J. (2004b). SOD2 Deficiency Anemia: Protein Oxidation and Altered Protein Expression Reveal Targets of Damage, Stress Response and Anti-oxidant Responsiveness. Prepublished online as Blood First Edition Paper, June 17, 2004 Blood.

Friedman, J. S., Rebel, V. I., Derby, R., Bell, K., Huang, T. T., Kuypers, F. A., Epstein, C. J., and Burakoff, S. J. (2001). Absence of mitochondrial superoxide dismutase results in a murine hemolytic anemia responsive to therapy with a catalytic antioxidant. J Exp Med 193, 925-934.