|Institution||College of Medicine|
|Address||500 University Drive Hershey PA 17033|
B.S., Millersville University, 1995
Ph.D., Pennsylvania State University College of Medicine, 2002
Postdoctoral Studies, Pennsylvania State University College of Medicine, 2008
Development of small-molecule sphingosine kinase inhibitors, role of sphingosine kinase in development/progression of tobacco-carcinogen induced lung cancer.
The primary research interest of our laboratory is focused on the identification of mechanisms involved in the oncogenic role of sphingosine kinase (SK). In cancer cells, dysregulation of cell growth and/or apoptosis is closely linked to the sphingolipid metabolites, ceramide and sphingosine-l-phosphate (S-1-P). Ceramide induces cell growth arrest and apoptosis whereas S-1-P, a further metabolite of ceramide, promotes cell growth and/or protects from apoptosis. Ample evidence indicates that S-1-P, formed by activation of SK, can serve as an intracellular second messenger which modulates signaling pathways critical for cancer cell growth and survival. In fact, S-1-P antagonizes apoptosis mediated by ceramide, a stress-induced sphingolipid metabolite, suggesting that the intracellular ratio of these two sphingolipid metabolites and consequent regulation of opposing signaling pathways, are important factors that determine the fate of cancer cells. It is our hypothesis that SK, which catalyzes formation of S-1-P, plays a pivotal role in regulation of cancer cell proliferation and/or survival. Currently, we are developing/optimizing small-molecule inhibitors of SK as anti-cancer therapeutic agents. Additionally, we are exploring the role of SK in the development and/or progression of lung cancer caused by carcinogens present in tobacco smoke. Understanding the role of SK in this process will allow us to validate our novel small-molecule SK inhibitors as potential anti-lung cancer therapeutic agents.
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