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Dr. Mehendale's research has one main goal: to determine the role of restorative tissue repair that follow initiation of tissue injury in toxic outcomes. Because these mechanisms are not fully understood, we are unable to accurately predict the risk from exposure to toxic chemicals. while the mechanisms of toxicant-initiated tissue injury are largely known, the mechanisms of progression/regression of toxicity that lead to the ultimate outcome of that injury are incompletely understood.

Outcome of injury lies within the two outer bounds of recovery or death. Acute or chronic illnesses, organ or tissue failure, benign or cancerous growth are some examples of the outcomes of injury that lie within these outer bounds. In protecting public health we are interested in preventing injury, but after injury our interest lies in maximizing the chance of recovery without any acute or chronic illnesses. Accurate and reliable prediction of these outcomes at low levels of exposure is a major challenge. Exposure to toxic chemicals may lead to injury initiated by mechanisms that are known. Simultaneously there is a compensatory endogenous response leading to cell division for repair of the injured tissues, thereby restoring the structure and function of the organs such as liver, kidney and lung. while low doses of toxicants stimulate tissue repair thereby overcoming the injury, high doses inhibit it causing an unrestrained progression of injury culminating in organ failure and death. Dose-response studies suggest that instead of measuring only injury as is classically done in dose-response studies, measuring the opposing tissue repair response in the dose-response paradigms might yield more meaningful information for accurate assessment of risk. Animal models of diabetes, obesity, caloric restriction and nonalcoholic steatohepatitis, are used for these investigations. Cell signaling mechanisms, gene expression, and proteomics in stimulation of restorative tissue repair are being investigated using model toxicants.