Stanley R. Terlecky, Ph.D.
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 as a postdoctoral fellow with Dr. Daniel Klionsky. She then joined Genomic Solutions in Ann Arbor as a staff scientist. Currently, she is Senior Research Associate in the Department of Orthopedics at the Children’s Hospital of Michigan. After graduating, Dr. Koepke joined EXT Life Sciences, Inc., a biotechnology company in Detroit. Currently, he is Professor of Biology at Edison State College in Naples, Florida. 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.
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.
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, 128: 2606-2614.
Koepke, J.I., Wood, C.S., Terlecky, L.J., Walton, P.A., and Terlecky, S.R. (2008) Progeric effects of catalase inactivation in human cells. Toxicology and Applied Pharmacology, 232: 99-108.
Price, M., Terlecky, S.R., and Kessel, D. (2009) A role for hydrogen peroxide in the pro-apoptotic effects of photodynamic therapy. Photochemistry and Photobiology, 85: 1491-1496.
Zhong, Q., Terlecky, S.R., and Lash, L.H. (2009) Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury. Toxicology and Applied Pharmacology, 241: 1-13.
Terlecky, S.R. and Walton, P.A. (Inventors); Wayne State University (Owner). Promotion of Peroxisomal Catalase Function in Cells. United States patent issued in 2009 (#7601366). European Union patent approved; Singapore patent issued; New Zealand patent approved.