DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Epigenetic Regulation of Immunogenic Endogenous Retrovirus (ERV) by Histone Demethylase KDM5B in Melanoma

Principal Investigator: ZHANG, SHANG-MIN
Institution Receiving Award: YALE UNIVERSITY
Program: MRP
Proposal Number: ME190335
Award Number: W81XWH-20-1-0360
Funding Mechanism: Concept Award
Partnering Awards:
Award Amount: $125,624.00


PUBLIC ABSTRACT

Immunotherapies have potent efficacy in melanoma patients who respond to the treatments. However, not all melanoma patients respond to current immunotherapies. There is an urgent need to identify and characterize novel drug targets to improve the response rate of immunotherapies. KDM5B demethylase is an attractive drug target, as its inhibition has been shown to induce immune responses. The goal of this proposal is to evaluate whether and how KDM5B regulates endogenous retrovirus in both human and mouse melanoma cells. This proposal will elucidate detailed mechanisms by which KDM5B loss in melanoma cells could induce endogenous retrovirus expression, activate anti-tumor immunity, and prime the host immune system to immunotherapy, thus converting non-responders to responders. In summary, the proposed studies will provide fundamental insights into how therapies directly targeting KDM5B could be a potential strategy to improve the response rates to checkpoint blockades in melanoma patients.