Dr. Curtis R. Pickering
The University of Texas MD Anderson Cancer Center
Department of Head and Neck Surgery
My research program is focused on the translational genomics of head and neck cancer. This lethal and debilitating disease is still treated primarily with surgery, chemotherapy and/or radiation. Our goal is to improve the treatment of head and neck cancer by understanding the genomic alterations that drive the disease.
Our translational research process starts with patient samples or data from previous patient studies, i.e. TCGA. We have recently characterized the spectrum of genomic alterations in oral tongue cancer and squamous skin cancer. These studies identified numerous genes of unknown clinical and functional relevance; including NOTCH1, CASP8, FAT1 and AJUBA. These top candidate alterations are now being studied functionally in the laboratory. We are also performing high-throughput functional genomic screens to rapidly detect additional key genes. Finally, pathway analysis has suggested that many of these genes regulate squamous differentiation, and this hypothesis is being investigated in a 3-dimensional organotypic raft culture system.
A rotation project could include initial in vitro validation of a new hit from the screens. The goal would be to generate enough in vitro data to justify in vivo validation, which could potentially be started during the rotation, depending on timing. Another possible rotation project would be to work with a hit that has already been validated in vivo (we have a few genes in various stages of validation). The goal would be to further understand the key pathways related to that hit and how they are controlling tumorigenicity or drug response. Depending on the gene, experiments could also be performed to determine if the gene/pathway is a reasonable therapeutic target. Finally, a more computational project could involve integrated analysis of the screening data with multiplatform genomic data on the cell lines and TCGA HNSCC patients. The goal of this project would be to identify additional screening hits that are linked to key genomic alterations or pathways and could lead to targeted therapeutic interventions or novel biomarkers. All of these rotation projects could involve analysis of shRNA screening data, analysis of cell line and TCGA genomic data, cell and molecular biology techniques related to tumorigenicity and/or drug response, and in vivo mouse xenograft experiments.