Broadly, our previous and current work focuses on identifying targetable drivers of resistance to radiation. Our laboratory is currently focused on several projects related to this question. We are fortunate to be funded by three separate R01 grants (R01CA16848, R01DE028105, & R01DE028061) as well as generous institutional support.
IMPROVING SYNERGY BETWEEN IMMUNOTHERAPY AND RADIATION
Despite the promise of immunotherapy in solid tumors, the optimal combination of this treatment with standard chemotherapy and radiation is unclear. Previously, we have identified tumor PD-L1 expression as associated with resistance to standard radiation in head and neck cancer, and effect that appears to be associated with T-cell exhaustion. In this project we are utilizing medium-throughput screening and tumor immune profiling to both evaluate how PD-L1 expression leads to resistance to standard radiation as well as identify novel targets to improve response to standard radiation as well as abscopal responses following stereotactic radiation (SBRT)
SYNTHETIC LETHAL TARGETING OF CREBBP/EP300 IN HEAD AND NECK SQUAMOUS CELL CARCINOMA
Recently we have identified mutations in the histone acetyltransferases (HATs) p300 and CBP as associated with resistance to standard radiation. Moreover, tumors harboring these mutations appear to be exquisitely sensitive to the combination of radiation and HAT inhibition. This project seeks to identify the mechanism underlying this observation.
USING INSIGHTS FROM HUMAN PAPILLOMAVIRUS (HPV) POSITIVE HEAD AND NECK CANER TO IMPROVE RESPONSES TO TREATMENT
Human papillomavirus (HPV) positive head and neck cancer (HNSCC) is highly sensitive to DNA- damaging therapy and is characterized by high expression levels of of p16. We have identified a novel pathway linking high levels of p16 expression with impaired homologous recombination following radiation therapy. By further characterizing this pathway we hope to identify targetable signaling nodes, to render HPV negative HNSCC more sensitive to treatment.