Research Initiation Awards provide support for junior and mid-career faculty at Historically Black Colleges and Universities who are building new research programs or redirecting and rebuilding existing research programs. It is expected that the award will (1) further the faculty member's research capability and effectiveness, (2) improve research and teaching at the home institution, and (3) engage more undergraduate students from underrepresented groups in research experiences. The project from Texas Southern University, a Historically Black College/University (HBCU), seeks to study the non-apoptotic functions of the Fas-associated protein with death domain (FADD) protein in osteosarcoma (OS) biology. The specific objectives include the investigation of (1) the mechanism of action responsible for death ligand-induced cell death; and (2) the role of FADD in cellular homeostatic activities. The project includes mentoring two Texas Southern University undergraduate students in research experience.
Fas-associated protein with death domain was initially discovered as an adaptor protein that facilitates Fas-mediated apoptosis. Subsequent studies reported non-apoptotic functions of FADD in immune cells. Non-apoptotic functions of FADD have not been extensively studied in cancer, and no reports are available on non-apoptotic functions of FADD in osteosarcoma (OS). Osteosarcoma is the most common type of bone cancer found in children and teens. The Principle Investigator has previously reported that decreased FADD expression sensitizes OS to death ligand-induced cell death, indicating that FADD protects OS against death ligand-induced cell death. The aim of this study is to investigate the non-apoptotic functions of FADD as well as the signaling pathways associated with the non-apoptotic functions of FADD in cancer, specifically OS. The specific objectives of this research are: 1) to determine the mechanism of action responsible for death ligand-induced cell death in OS with altered FADD status and 2) to elucidate the function of FADD in cell homeostasis to include regulation of oxidative stress, cell proliferation and regulation of cell cycle. Level of FADD expression, cellular localization of FADD and FADD phosphorylation affects FADD function. To investigate the non-apoptotic functions of FADD, three OS cell models will be used: 1) cells with reduced expression of FADD, 2) cells with impaired nuclear localization of FADD, and 3) cells with inhibited FADD phosphorylation. The experimental approach presented investigates the different cellular states of FADD that affect FADD function. Assessment of pro-survival and pro-death signaling pathways and expression of pro-survival and pro-death molecules will elucidate mechanisms responsible for death ligand-induced cell death in OS with altered FADD status. Cell growth, cell viability, metabolic activity, and cell cycle regulation in the three OS cell models will be assessed to determine the impact of altered FADD status on cell homeostasis. The results generated from this investigation will contribute to a better understanding of FADD function in OS and will serve as a basis for the direction of research on the biological function of FADD in other cancers.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.