Research Summary
I am Professor of Otolaryngology-Head and Neck Surgery and Associate Vice Chancellor for Clinical and Translational Research at UCSF, where I also direct the Clinical and Translational Science Institute (CTSI). My own research efforts are focused on elucidating and targeting key signaling pathways in head and neck cancer. I directed the head and neck cancer program at the University of Pittsburgh Cancer Institute from 1998-2014 and in this capacity facilitated collaborations between clinicians and investigators with an emphasis of developing a robust research infrastructure to support translational cancer studies. I served as PI of the SPORE in Head and Neck Cancer at the University of Pittsburgh from 2002-2014 and now serve as Co-PI of that SPORE in a multi-PI structure. I am a member of the Developmental Therapeutics Program at the HDFCCC and facilitate interactions between the cancer center and the CTSI.

Dr. Grandis's is dedicated to increasing our understanding of the genetic and epigenetic alterations in the upper aerodigestive tract mucosa, which mediate head and neck squamous cell carcinoma (HNSCC) progression. The overall goal is to identify predictive biomarkers, which can serve to select patients for therapies, including molecular targeting approaches. Translational resources developed to support projects include a large collection of patient-derived xenografts (PDXs) and tissue microarrays of over 500 human HNSCCs linked to a professionally curated clinical and pathologic database that includes information on treatment and survival. To date, the have examined the role of the epidermal growth factor receptor (EGFR), it’s ligands coordinate activation of STAT3 (signal transducer and activator of transcription) in head and neck carcinogenesis. Cumulative evidence from her laboratory suggests that TGF-?lpha/EGFR autocrine signaling leading to STAT3 activation is as early event in head and neck carcinogenesis. Strategies aimed at blocking the ligand, receptor or signaling protein demonstrated anti-tumor efficacy in preclinical models. Based on these promising results, they completed a Phase I clinical trial to investigate the toxicity and biologic effects of EGFR antisense gene therapy and a Phase II study was recently closed to accrual. They have developed STAT3 targeting strategies using a decoy oligonucleotide approach and early phase clinical testing demonstrated feasibility without toxicity. Ongoing studies are aimed at identifying the targetable genetic alterations in these cancers with the goal of designing precision medicine approaches. Emerging targets include activating mutations of the PI3K signaling pathway, primarily in HNSCC linked to HPV infection and mutation or promoter hypermethylation of selected PTPRs, which lead to STAT3 activation.

Primary Thematic Area:
Cancer Biology & Cell Signaling
Secondary Thematic Area:
Human Genetics
Research Summary:
Translational Head and Neck Cancer Research