The candidate, Dr. Lawrence Lash, is an Assistant Professor in the Department of Pharmacology at Wayne State University School of Medicine. Dr. Lash has established an active research program on biochemical mechanisms of nephrotoxicity. His research is currently supported by a FIRST Award from NIH (1988-1993) and he was the recipient of a Pharmaceutical Manufacturers Foundation Association Research Starter Award (1988-1989). During Dr. Lash's research career he has made significant contributions toward our understanding of the roles of renal glutathione in physiological and toxicological processes and of the mechanistic basis of chemical-induced nephrotoxicity. He has established two research collaborations which ave resulted in applications of new techniques in his research program. In the four years since joining the faculty, Dr. Lash has become very active in departmental programs and activities. Dr. Lash's immediate career goals are to continue developing his research program and his professional collaborations and thereby establish himself further as a recognized researcher in the area of biochemical toxicology. In preliminary studies, Dr. Lash's laboratory has established primary cultures of renal proximal tubular cells as an in vitro model system to study chronic toxicity and carcinogenesis. This new methodology provides opportunities for expansion and an increased sophistication in the research program. His long-term career goals are to maintain an active research program, learn new techniques, foster new research collaborations, become more active in the scientific community, and become more involved in the training of students and postdoctoral fellows. Dr. Lash is one of only two Assistant Professors and one of only three non-tenured faculty members in a department of eighteen full- time faculty. Receipt of a Research Career Development Award will provide more job security but more importantly, will allow the candidate to spend more time in development of his research program, in fostering collaborations, and in learning new techniques and research approaches. If given this award, the Department of Pharmacology will support the research development of the candidate by requiring less participation in departmental committees and teaching, reducing non-research obligations to 10 to 15% of effort, and by allowing the candidate to spend brief periods of time (one to four months) at other laboratories learning new methodology. The research that will be performed during the tenure of this proposed award will involve a continuation of studies in freshly isolated renal cells on the biochemical basis of cellular susceptibility to various forms of acute injury produced by toxic chemicals and pathological conditions and new studies on development of primary cultures of renal cells from specific nephron regions and their use in the study of biochemical mechanisms of chronic toxicity.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Modified Research Career Development Award (K04)
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Toxicology Subcommittee 2 (TOX)
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Wayne State University
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United States
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Lash, L H; Putt, D A; Brashear, W T et al. (1999) Identification of S-(1,2-dichlorovinyl)glutathione in the blood of human volunteers exposed to trichloroethylene. J Toxicol Environ Health A 56:1-21
Cummings, B S; Zangar, R C; Novak, R F et al. (1999) Cellular distribution of cytochromes P-450 in the rat kidney. Drug Metab Dispos 27:542-8
Lash, L H; Lipscomb, J C; Putt, D A et al. (1999) Glutathione conjugation of trichloroethylene in human liver and kidney: kinetics and individual variation. Drug Metab Dispos 27:351-9
Lash, L H; Putt, D A (1999) Renal cellular transport of exogenous glutathione: heterogeneity at physiological and pharmacological concentrations. Biochem Pharmacol 58:897-907
Lash, L H; Qian, W; Putt, D A et al. (1998) Glutathione conjugation of trichloroethylene in rats and mice: sex-, species-, and tissue-dependent differences. Drug Metab Dispos 26:12-9
Lash, L H; Putt, D A; Zalups, R K (1998) Role of extracellular thiols in accumulation and distribution of inorganic mercury in rat renal proximal and distal tubular cells. J Pharmacol Exp Ther 285:1039-50
Lash, L H (1998) In vitro methods of assessing renal damage. Toxicol Pathol 26:33-42
Chen, Z; Lash, L H (1998) Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2-oxoglutarate carriers. J Pharmacol Exp Ther 285:608-18
Lash, L H; Qian, W; Putt, D A et al. (1998) Glutathione conjugation of perchloroethylene in rats and mice in vitro: sex-, species-, and tissue-dependent differences. Toxicol Appl Pharmacol 150:49-57
Lash, L H; Visarius, T M; Sall, J M et al. (1998) Cellular and subcellular heterogeneity of glutathione metabolism and transport in rat kidney cells. Toxicology 130:1-15

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