• Genomics
• Tumor biology
• Metabolism
• Molecular & cell biology
• Tumor progression and metastases
• Animal models
• Therapeutics

Our group pursues novel approaches to identify the most treatment-refractory cases  of head and neck cancer prospectively and address their mechanisms of therapy resistance. At the same time, we are working to develop biomarkers that allow de-escalation of therapy and abatement of treatment toxicity for treatment-sensitive patients. Our lab’s efforts span both the  HPV-related subtype of oropharyngeal cancer, which is rapidly growing in incidence, and the generally more aggressive HPV-negative cancers. Our recent work to create experimental cancer models has emphasized the HPV+ cancer subtype. We have partly overcome the poor growth potential of HPV+ oropharyngeal tumors outside patients to establish a unique panel of patient derived xenografts (PDXs) as well as multiple organoid and primary culture models. Our studies with these tools emphasize targeting mechanisms of tumor progression and treatment resistance that depend upon cooperativity among multiple tumor cell states. In the process, we have developed the expertise for analyzing the heterogeneity and phenotypic plasticity within and among HPV+ oropharyngeal cancer cell lines, organoids, PDXs, and primary human cancer samples based on molecular and functional criteria. Using such models, our group seeks precise molecular definition of the tumor cell state dynamics that sustain malignant potential of an aggressive subset of these cancers in the face of therapy. Our recent efforts extend to understanding implications of the widely variable viral oncogene expression levels seen among different HPV+ tumors. We are presently working closely with collaborators with expertise in HPV oncogene function and mitochondrial biology to explore the mechanistic relationships between levels of  viral oncoprotein expression and therapy responses. In addition, we are seeking related prognostic and therapeutic biomarkers in distinct but complementary studies using a large cohort of patients who underwent transoral robotic surgical removal of HPV+ oropharyngeal cancers.