Investigators within the Cancer Biology are studying mechanisms of tumorigenesis and metastasis both in animal models and through genomic, epigenomic, and proteomic study of primary human cancer. Topics of interest include the identification of novel cancer-promoting pathways through the study of transcriptional control elements, stem cell regulation in carcinogenesis, molecular mechanisms that integrate cell adhesion with tumor invasion and metastasis, and the improved assessment of human disease with respect to prognosis and therapy to optimize initial treatment decisions.
Evidence has now established that aberrant DNA methylation and chromatin remodeling associated with promoters, or first exons of genes, is one mechanism frequently associated with the transcriptional silencing of critical genes in HNSCC and other cancers. One goal of our lab is the genome-wide analysis of aberrant DNA methylation events in head and neck tumor genomes. These “epigenetic signatures” can be used to identify CpG island sequences frequently hypermethylated in HNSCC, and to characterize previously indistinguishable subtypes of this disease. The long-term goal of our research is to identify genetic and epigenetic signatures associated with successful treatment and patient outcome in this disease, as well as those signatures that indicate that drug treatment will not work. This should lead to more unique gene discoveries and, in the future, new targets for anti-tumor drugs.
Cell-cell adhesion is a primary modulator of morphogenetic events during normal embryonic development. Metastatic dissemination of epithelial tumor cells is also strongly influenced by the activity of cell-cell adhesion molecules, in particular members of the cadherin family. My laboratory has shown that N-cadherin, a cadherin involved in dynamic processes such as cell migration and neurite outgrowth, is upregulated in invasive breast cancer cells and promotes metastasis of breast cancer cell lines. My laboratory is currently investigating: 1) the molecular basis for cooperation between N-cadherin and the FGF receptor responsible for epithelial to mesenchymal transition (EMT) and metastasis with the goal of obtaining functional inhibitors of metastasis. 2) Regulation of EMT and metastasis by the MAPK and AKT signaling pathways 3) the relationship between cell cycle progression and tumor metastasis. 4) The mechanism of HER2 therapeutic resistance in breast cancer. 5) Cancer stem cells and their role in breast cancer metastasis.
Our laboratory uses modern genomics to better understand the role of human genetic variations in these processes. Our mission is to lay the groundwork for future development of therapies based on our research.
The Head and Neck Program includes multiple laboratories with research exploring basic mechanisms of tumor behavior, developing biomarkers and identifying molecular classifiers that define distinct subsets of patients. Studies in the Prystowsky Laboratory focus on identifying proteomic signatures that predict tumor behavior.