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Stanley R. Terlecky, Ph.D.
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RESEARCH INTERESTS:
The long-term goals of our laboratory are to understand peroxisome biogenesis and function in human health, disease, and aging. Peroxisomes are vital intracellular organelles involved in a vast array of biochemical and metabolic processes. The existence of devastating genetic disorders in which peroxisomes fail to import their matrix enzymes and are thus functionally compromised perhaps best illustrates the importance of the organelles in overall human physiology. Importantly, our work has also identified a previously unrecognized role for the organelle in cellular aging events.
In collaboration with Dr. Paul A. Walton from the University of Western Ontario, we employed our expertise in cellular trafficking mechanisms to create a novel protein therapeutic based on a cell-permeable derivative of the peroxisomal antioxidant, catalase. The drug appears to possess broad applicability to a variety of age-related pathologies that result form the accumulation of reactive oxygen species and attendant cellular damage. The patent-pending compound’s efficacy in treating several clinical indications including psoriasis and related skin disease, skin aging, osteoarthritis and degenerative joint disease, ischemia-reperfusion injury to the heart, inflammation, and neurodegenerative disease are currently being explored both in the laboratory here at the School of Medicine and in conjunction with a number of pharmaceutical-, biotechnology-, and life science-based research companies.
Students trained in the laboratory:
Four students have completed their doctoral degrees in the laboratory including, Julie E. Legakis (2003), Jay I. Koepke (2006), Christopher S. Wood (2006), and Chen N. Young (2007). Dr. Legakis went on to the University of Michigan and is now a scientist at Genomic Solutions in Ann Arbor. Dr. Koepke is a staff scientist at EXT Life Sciences, Inc. in Detroit. Dr. Wood is a postdoctoral fellow at the University of Pennsylvania School of Medicine in Philadelphia and Dr. Young is a Health Sciences Specialist at the John D. Dingell VA Medical Center and an Adjunct Assistant Professor in the Department of Dermatology at the Wayne State University School of Medicine.
Recent publications:
Wood, C.S., Koepke, J. I., Teng, H., Boucher, K.K., Katz, S., Chang, P., Terlecky, L.J., Papanyotou, I., Walton, P.A., and Terlecky, S.R. (2006) Hypocatalasemic fibroblasts accumulate hydrogen peroxide and display age-associated pathologies. Traffic, 7: 97-107.
Terlecky, S.R. and Walton, P.A. (2006) Peroxisomes and aging. Biochimica et Biophysica Acta, 1763: 1749-1754.
Koepke, J.I., Nakreiko, K.A., Wood, C.S., Boucher, K.K., Terlecky, L.J., Walton, P.A., and Terlecky, S.R. (2007) Restoration of peroxisomal catalase import in a model of human cellular aging. Traffic, 8: 1590-1600.
Terlecky, S.R. and Koepke, J.I. (2007) Drug delivery to peroxisomes: employing unique trafficking mechanisms to target protein therapeutics. Advanced Drug Delivery Reviews, 59: 739-747.
Chen N. Young, C.N., Koepke, J.I., Terlecky, L.J., Borkin, M.S., Savoy, L.B., and Terlecky, S.R. (2008) Reactive oxygen species in TNF-a-activated primary human keratinocytes: implications for psoriasis and inflammatory skin disease. Journal of Investigative Dermatology, in press. (Epub ahead of print available: PMID: 18463678)
Search PubMed for publications from the Terlecky Lab
Patents:
Terlecky, S.R. and Walton, P.A. (Inventors); Wayne State University (Owner). Promotion of Peroxisomal Catalase Function in Cells. United States patent pending (published application number – 20060141598).
