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David Orren, Ph.D

Associate Professor
Graduate Center for Toxicology

Mailing Address:
Graduate Center for Toxicology
1095 V.A. Drive
306 Health Sciences Research Building
Lexington, KY  40536-0305
Office: 356 HSRB
Phone: (859) 323-3612
Fax: (859) 323-1059

Research Interests

Our focus of study is how endogenous processes and environmental agents contribute to genetic changes that, in turn, lead to carcinogenesis and other characteristics of human aging. We are currently using cancer-prone and premature aging diseases as model systems to examine these processes. Of particular interest to our laboratory are hereditary diseases such as Werner syndrome that are caused by deficiencies in RecQ helicase genes. Individuals with Werner syndrome have an early onset and accelerated development of many aging characteristics (including an increased frequency of cancer and atherosclerosis). Intriguingly, all of these changes appear to be the result of defects in a single protein known as WRN. WRN has the ability to unwind double-stranded DNA (helicase) and degrade one strand of a DNA duplex substrate (exonuclease), indicating an (as yet) unknown function in DNA metabolism. The lack of WRN function leads to accumulation of chromosomal abnormalities, accelerated loss of telomeric DNA sequences, and reduced cellular replicative capacity (premature senescence). The phenotypes of Werner syndrome and other RecQ helicase deficiencies solidify the connection between the accumulation of genetic changes during life and the appearance of at least some characteristics of human aging. By examining these connections, we also hope to gain insight into how the normal aging process occurs and possibly design strategies to slow the debilitating processes that occur in later life.

For a list of Dr. Orren's publications, please visit the PubMed web site.

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