Walter Klimecki

The focus of Dr. Klimecki's research program is the complicated balance between the particular DNA sequence “versions” of genes that we inherit from our ancestors, and the particular environmental exposures that we experience throughout our lives. Viewed broadly, those environmental exposures include many chemicals, some (like prescription drugs) with intentional exposures and some (like environmental toxicants) with unintended exposures. Toxicity resulting from these exposures is often a combination of the particular versions of genes that we inherit that produce our own unique biological systems, together with the underlying mechanisms by which chemicals can damage biological systems. The Klimecki research group studies this complex problem from both vantage points, which Dr. Klimecki summarizes below:

“Because of our interest in diseases resulting from human exposure to arsenic, a toxic exposure important in Arizona, our research has contributed to a better understanding of the inherited genetic differences between people that result in altered chemical processing of arsenic after it enters the body. In all likelihood, much of the arsenic-induced damage happens from chemical forms of arsenic that our bodies create, not the original chemical form that we find in drinking water. Understanding how human genetics determines our particular ways of creating modified chemical forms of arsenic is important to understand how arsenic causes disease, and who is most likely to be particularly sensitive to arsenic.

"At the same time, we are also studying the biological systems that are damaged by arsenic, leading to disease. In particular our recent work has established a novel pathway called autophagy as a target for arsenic-induced damage. Autophagy is a 'cash for clunkers' program in the cell.  Components of the cell that are old and targeted for disposal are delivered to an organelle called the lysosome, where they are broken down to their component parts, and those parts are then recycled to build newer cellular structures that the cell needs. Disruption of this process has been linked to a diverse array of diseases, including cancer, diabetes, and cardiovascular disease. The ability of arsenic to disrupt autophagy offers new explanations of how arsenic makes people sick.”