Our lab is dedicated to understanding the mechanisms that underlie the growth, development, and spread of head and neck cancers and to determine how these mechanisms may be targeted to develop new diagnostics and therapeutics for this devastating disease. Please see our research vision for a broad overview of our overarching goals. Briefly, we aim to expand the field of head and neck oncology through several major lines of research:
Characterize expression and epigenetic heterogeneity in head and neck cancer
Using cutting edge single cell techniques, which our lab has pioneered, we will investigate diversity present at the level of diverse individual cells, including malignant, stromal, and immune subpopulations. Although we have begun the difficult work of studying heterogeneity in oral cavity tumors, other subsite of HNSCC as well as other pathologies could greatly benefit from these studies. Future work will extend to deep analyses of epigenetic heterogeneity to complement studies of expression heterogeneity.
Develop in vitro and in vivo models to study head and neck cancer
Despite substantial interest there are few typified and widely accepted models of head and neck cancer. With access to numerous cell lines, we will characterize existing models in new ways using a combination of mutational and expression-based profiling, thereby validating how well these models recapitulate human tumors and their diversity. However, we are interested in developing more sophisticated models of these human cancers through patient-derived xenografts (PDX) and potentially syngeneic models that may better allow the immune system and its influence in head and neck cancer to be more accurately studied.
Define the pathways that drive head and neck cancer metastasis, treatment resistance, self-renewal, and immunotherapy response
Our prior work has identified a role for a partial epithelial-to-mesenchymal program in head and neck tumors, specifically oral cavity head and neck squamous cell carcinoma. We will use this foundational work as a starting point and by leveraging standard genetic and biochemical techniques, study this pathway in greater detail including its role in tumor invasion and locoregional and distant metastasis. In the future, we will investigate additional pathways in head and neck cancer that may define drug resistance, self-renewal capabilities, and immunotherapy response.
Translating findings into new diagnostics and therapeutics
Due in part to Dr. Puram’s clinical interests, we are highly motivated and well positioned to translate findings from our lab into meaningful changes in patient care. Through large scale pathologic studies using ISH and IHC combined with cutting edge technologies such as multiplexed imaging, we can begin to characterize potential biomarkers in head and neck cancer, while simultaneously utilizing traditional tools in drug discovery to identify targets for novel therapeutics. Our ultimate goal is to move our findings into early pre-clinical and clinical trials that will ultimately dramatically influence the way we manage this challenging disease.