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Lawrence H. Lash, Ph.D. |
RESEARCH INTERESTS:
Dr. Lash’s research program over the past nearly three decades has focused on various aspects of determining how chemicals produce injury to the kidneys and how we can design approaches to preventing or correcting such injury. The kidneys are critical for the maintenance of electrolyte and acid-base balance in the body and for reabsorption of nutrients and excretion of waste products. Because of the manner by which these functions are accomplished, the kidneys are very susceptible to injury from many types of chemicals. Consequently, a good understanding of how the kidneys handle and respond to drugs and other chemicals (in physiological, biochemical, and molecular terms) is necessary. Kidney injury can take the form of acute toxicity with failure of organ or cellular function, or chronic toxicity, which may be characterized by decreased organ or cellular function or transformation of kidney cells into tumor cells. Acute toxicity typically occurs with exposures to relatively high doses of chemicals over short periods of time whereas chronic toxicity typically involves exposures to relatively lower doses of chemicals over longer periods of time. The first situation is analogous to overdose exposures to either a drug or environmental chemical or to an accidental exposure to a high amount of an environmental and/or industrial chemical in the workplace. In contrast, the second situation is analogous to a continual or long-term exposure to a relatively low dose of an environmental or industrial chemical.
The chemicals that we have used to produce kidney toxicity fall into one of three categories: 1) Model chemicals that are used to study specific mechanisms of action; 2) pharmacologic agents, such as analgesics or antibiotics; and 3) environmental chemicals, such are trichloroethylene and perchloroethylene. Although some of our studies have been conducted in intact, experimental animals, most of our studies have involved a variety of in vitro systems, including freshly isolated and primary cultures of kidney cells from rats and humans, subcellular fractions, or purified proteins. These type of in vitro model systems have afforded us the opportunity to dissect biochemical and molecular mechanisms of action and to manipulate and specify incubation conditions. Moreover, it is important to note that we have validated these in vitro model systems in terms of their functional integrity and relevance to the normal, in vivo state. More
Selected Recent References.
L.H. Lash, D.A. Putt, S.E. Hueni and B.P. Horwitz: Molecular markers of trichloroethylene-induced toxicity in human kidney cells. Toxicol. Appl. Pharmacol. 206, 157-168 (2005). PubMed
L.H. Lash: Mitochondrial glutathione transport: Physiological, pathological and toxicological implications. Chem.-Biol. Interact. 163, 54-67 (2006). PubMed
L.H. Lash, D.A. Putt and H. Cai: Membrane transport function in primary cultures of human proximal tubular cells. Toxicology 228, 200-218 (2006). PubMed
Q. Zhong and L.H. Lash: Mitochondrial glutathione transport in diabetic nephropathy. Nephroprevention 2, http://www.nephroprevention.org/ (2007).
L.H. Lash, D.A. Putt and H. Cai: Drug metabolism enzyme expression and activity in primary cultures of human proximal tubular cells. Toxicology 244, 56-65 (2008). PubMed
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