Sphingolipid Program Project Grant

group photo of sphingolipid ppg team members

The overall goal of this multidisciplinary and clinically significant program project funded by the National Cancer Institute is to develop novel cancer therapeutics by targeting sphingolipid signaling. Researchers will determine common signaling mechanisms regulated by sphingosine-1-phosphate (S1P) that induce cancer cell proliferation, resistance to therapy, and metastasis in solid tumors.

Besim Ogretmen

Principal Investigator Besim Ogretmen, Ph.D., leads the program project grant along with project leaders, core leaders, and both internal and external advisory board members from leading academic institutions. The therapeutic goal is to use the information gained from these studies to develop novel treatments for patients with solid tumors, such as prostate, urinary, and/or liver cancers, by targeting pro-survival S1P signaling.

This program is designed to test the novel overall hypothesis through three unique projects, including a Phase II clinical trial, integrating four essential cores. The program’s three projects focus on overcoming therapeutic resistance and preventing relapse in solid tumors, inhibiting the cancer’s spread to other parts of the body, and uncovering how sphingosine kinase (SK) inhibitors can best be used for treating liver cancer.

These projects are led by a multidisciplinary team with expertise spanning microbiology, immunology, biochemistry, molecular biology, surgery, biostatistics, and more. Learn more about the program’s current studies and leadership team.

Program Goals

  • Dissect the mechanisms by which induction of SK1/S1P in response to acid ceramidase activation mediates resistance to radiation and/or chemotherapy via AKT/PTEN signaling.
  • Define how cancer cells communicate with the host organism and induce tumor metastasis via S1P/S1PR and C5a/C5aR-complement signaling.
  • Determine the mechanisms of nuclear SK2/S1P signaling to induce c-Myc stability and cancer cell proliferation.