Dr. Jeremy Hengst's research focuses on the development of small-molecule sphingosine kinase inhibitors and the role of sphingosine kinase in development/progression of tobacco-carcinogen-induced lung cancer.

The primary research interest of his laboratory is 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 that 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.

Hengst's lab hypothesizes that SK, which catalyzes formation of S-1-P, plays a pivotal role in regulation of cancer cell proliferation and/or survival. Currently, the lab is developing/optimizing small-molecule inhibitors of SK as anti-cancer therapeutic agents. Additionally, they 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 Dr. Hengst's lab to validate its novel small-molecule SK inhibitors as potential anti-lung cancer therapeutic agents.