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Name:	Dean P. Jones
Position:	Professor of Medicine
Degree:	Ph.D., Oregon Health Sciences University, 1976
Programs:	NHS, Full Member MSP, Full Member
Phone:	404 727-5970
Address:	4131 Rollins Research Center, 1510 Clifton Rd, 1941/001/1AJ
Email:	dpjones@emory.edu
Research Descriptions:
Short:	Diet and cancer; antioxidants and aging.
Long:	Studies are focused on molecular toxicology, with an emphasis on the role of mitochondria in apoptosis and nutritional approaches to enhance GSH-dependent detoxification systems. Many of these studies are performed in collaboration with members of clinical departments, with the intent to obtain data most relevant to improve treatment or prevent human pathologies and toxicities. Recent studies have addressed mitochondria superoxide production during apoptosis, the antioxidant functions of GSH in the retinal pigment epithelium in association with oxidative injury and the role of ascorbate in protection against hyperoxic injury in the lung. Apoptosis is now recognized to be the central mechanism of cell death induced by a wide range of toxic agents. We have found that mitochondria are central in this signaling pathway and that direct damage to mitochondria induces cytochrome c release and activation of caspases that commits cells to undergo this "programmed" cell death. The release of cytochrome c also switches electron flow to produce superoxide anion and therefore also results in a generalized oxidation in apoptotic cells. Studies of the retinal pigment epithelium are directed toward understanding the etiology and development of preventive strategies for age-related macular degeneration, a leading cause of vision loss in this country. We recently found that oxidants induce apoptosis in the human retinal pigment epithelium by activating the mitochondrial permeability transition. Studies of the mitochondrial genome indicate oxidant-induced deletions and rearrangements increase with aging in these cells. Recent findings as part of a multicenter interventional trial with antioxidants also show that blood plasma GSH declines with aging and that oxidation of this GSH pool is associated with increased risk of the disease. In vitro studies of human retinal pigment cells in culture show that dietary inducers increase GSH and decrease oxidant-induced injury, suggesting that interventions directed toward maintaining GSH may provide a rational approach to prevention. Our studies on antioxidants in the lung show that ascorbate and GSH protect against oxidant-induced apoptosis in primary cultures of lung cells. Of particular interest, ascorbate concentrations that are not scorbutic but just at the low end of normal (individuals in the lower 20th percentile of the normal range) result in increased susceptibility to oxidant-induced injury. Thus, the results indicate that concentrations of ascorbate needed for optimal antioxidant functions are higher than those needed to prevent scurvy. Ongoing collaborations with clinicians and epidemiologists address the roles of antioxidants in prevention of cancer and age-related diseases.