I am a basic scientist with a passion for exploiting the emerging information on dysregulated signaling circuitries and individual genomic and molecular alterations to identify new therapeutic options to prevent and treat cancer. Our basic studies and translational efforts have already made an impact in the development of individualized, mechanism-based molecular-targeted (precision) anticancer treatments and immunotherapeutic strategies.

My laboratory has focused on the study of growth-promoting signal transduction pathways, the nature of the dysregulated signaling networks in cancer with emphasis on head and neck cancer, and the use of genomic, proteomic, and system biology approaches to study cancer progression. The four primary research areas in our laboratory include the study of: 1) G proteins and GPCR signaling in cell growth control and cancer; 2) head and neck cancer (HNSCC); focused on precision prevention and treatment options; 3) immune oncology, with emphasis on the study of multimodal precision immunotherapies for HNSCC and other malignancies; and 4) the role of GPCRs in cancer immune evasion and as novel immunotherapeutic targets.

Specifically, we have shown that human and virally-encoded G proteins and G protein coupled receptors (GPCRs) can display potent oncogenic activity. Emerging evidence from our laboratory has revealed that malignant cells often hijack the normal physiological functions of GPCRs to proliferate autonomously, evade immune detection, enhance their nutrient and oxygen supply, invade their surrounding tissues, and disseminate to other organs. Strikingly, our recent analysis of human cancer genomes revealed an unanticipated high frequency of mutations in G proteins and GPCRs in most tumor types. Indeed, nearly 30% of all human cancers harbor mutations in GPCRs or G proteins. We are now investigating the mechanisms by which genetic mutations in Gαq proteins (encoded by the GNAQ oncogene) initiate uveal and cutaneous melanoma, the role of Gαs (encoded by the GNAS oncogene) and its target, PKA, in cancer, with emphasis on colorectal and pancreatic cancer, and how mutations and autocrine activation of GPCRs contribute to tumor progression, immune evasion, and therapy resistance. We are also harnessing the use of novel computational biology approaches to investigate the role of GPCRs in immunotherapy resistance and as novel immune oncology treatment strategies.

In parallel, we are exploring the role of the mTOR and Hippo pathways in head and neck cancer, a disease that results in 300,000 deaths each year worldwide. Based on our studies, and emerging results from our multi-institutional clinical trial targeting mTOR in oral cancer, we are now investigating the effectiveness and mechanism of action of PI3K/mTOR inhibitors for oral cancer prevention and treatment, as single agents and as part of novel signal transduction-based co-targeting strategies. We are also investigating new oral cancer treatment options targeting key signaling nodes in the Hippo pathway.

I am currently the Chair of the Department of Pharmacology, School of Medicine, and Associate Director of Basic Science, and Co-Director of the Head and Neck Cancer Center at the Moores Cancer Center at UCSD. Over the years, I have been fortunate to have the opportunity to work with a superb team of talented students, post-doctoral fellows, and outstanding collaborators, who share our passion for translating our findings (discoveries) into new, effective, safe, and low-cost precision targeted and immunotherapeutic strategies to prevent and treat human malignancies.