Research

Our research aims to create novel therapeutic combinations for head and neck cancer, with a focus on enhancing the anti-tumor immune response and decreasing treatment-related toxicity. We are also interested in repurposing drugs that are FDA-approved for other indications in order to create low-cost, well-tolerated therapeutic combinations for head and neck squamous cell carcinoma (HNSCC).

1. Drugs that block inhibitor of apoptosis protein (IAP) pathways are under active study as radiosensitizing drugs for HNSCC. Our lab has shown that that IAP antagonists, when paired with radiation, activate multiple facets of the anti-tumor immune response. We continue to evaluate the immune mechanisms of this promising combination in orthotopic mouse models and in biospecimens from a first-in-human clinical trial of radiation + tolinapant.
2. Statin drugs (used for hyperlipidemia) are associated with enhanced survival in HNSCC patients, for reasons that are not entirely understood. Our work suggests that some statin drugs can enhance the activity of T cells, especially when combined with immune checkpoint blockade. In collaboration with Dr. Cheng Zhu at Georgia Tech, we are working to better understand how statin therapy impacts the biophysical aspects of T cell receptor signaling.
3. In head and neck cancer, resistance to immunotherapy is largely driven by deficiencies in the machinery needed to process and present antigens to cytotoxic T lymphocytes. In collaboration with Dr. Gabriel Kwong at Georgia Tech, we are investigating innovative ways to restore the expression of this antigen processing machinery and in turn restore responses to immune checkpoint blockade and other forms of immunotherapy.
4. Chemoprevention of oral/laryngeal cancer is another area of interest. The presence of premalignant or “dysplastic” lesions represents an opportunity to intervene before these lesions progress into invasive carcinoma. We are currently studying whether blueberry extract, alone or with other promising chemoprevention agents, can slow or halt carcinogenesis or disease relapse in murine models of oral cancer.

A subset of effector memory cells (CD45RA+ or TEMRA cells) lacking costimulatory receptors appear to accumulate in cancer patients with age and with exposure to viral infection. Although these cells are frequently called “senescent” T cells, our work suggests that they maintain an ability to proliferate. We are working to better understand the origin, antigen specificity, and prognostic significance of these cells, which has growing importance as our population of older patients with cancer continues to increase.