Our research program focuses on the molecular genetics/genomics and biology of cancer genesis, maintenance and progression with emphasis on malignant melanoma and glioblastoma (GBM). Major oncoogenomic efforts in human and mouse are complemented by development of refined mouse models of human cancers for functional genomics and genetic screens, with the goal of accelerating validation and translation of multi-level genomic data, particularly in area of metastasis. Emerging areas of emphasis include development of biomarkers and preclinical therapeutic studies in model systems.

Mouse models of human cancers. Conditional transgenic and knockout technologies are used to engineer cancer relevant mutations in the mouse with the goal of generating cancer-prone conditions that recapitulate aspects of the human disease, particularly melanoma. Inducible tumor model where dominant acting oncogene is regulated in a time- and tissue-specific manner are used to characterize the roles of such oncogenic lesion in tumor genesis and maintenance, as well as to explore the complexity of host-tumor interactions. Introduction of genome instability through telomerase deficiency “humanizes” the mouse cancer genome for comparative oncogenomics. Importantly, these systems are leveraged to establish and optimize in vitro and in vivo genetic screen platforms for gene discovery and pathway dissection.

Oncogenomics. Development of array-based CGH technology and bioinformatic tools has been the early focus of this program, which is now a core component of the US cancer genome project TCGA (The Cancer Genes Atlas). The major goal has been the discovery of cancer-relevant genes. Many novel candidates are being studied on clinicopathological, functional and biological levels. In addition to developing systematic approaches to integrate data across species (e.g. mouse and human comparison) and across platforms (e.g. DNA copy number, mutations, methylation and RNA expression) to identify candidates, we continue to stay at the forefront of technology developing in genomics in order to further expand our view of the oncogenome with increasing accuracy and sensitivity. Moreover, alterations on the proteomic level are also being integrated.

Functional genomics. Beyond generation and gathering of genomic data, our goal is to functionalize such data for translation. Here, leveraging our cancer biology expertise and genetically engineered model systems, we are developing approaches to accelerate validation through high-content genetic screens. These include genome-wide RNAi screens or focused genetic elements screens based on genomic data triangulated with developmental or cancer biological insights using in vitro and in vivo model systems.

Genetics and biology of metastasis. One of the major areas of emphasis in our functional genomics program is metastasis. Utilizing mouse and human systems, our efforts are directed at (1) elucidating early genetic lesions in primary tumors that can drive the very processes of metastatic progression thus can be prognostic of future metastasis risks and (2) identifying progression drivers that are keys to enabling dissemination to distal organ sites.

Genetics and biology of metastasis. One of the major areas of emphasis in our functional genomics program is metastasis. Utilizing mouse and human systems, our efforts are directed at (1) elucidating early genetic lesions in primary tumors that can drive the very processes of metastatic progression thus can be prognostic of future metastasis risks and (2) identifying progression drivers that are keys to enabling dissemination to distal organ sites.