The University of Texas MD Anderson Cancer Center
Department of Genomic Medicine
- Cancer genomics/epigenomics
- Functional genomics
- System biology
- Tumor microenvironment
- Mouse models
Dr. Chin's research program focuses on the molecular biology and (epi)genetics/(epi)genomics of cancer genesis, maintenance and progression in multiple tumor types, with an emphasis on glioblastoma and melanoma. Major efforts to characterize the oncogenome in humans and mice are complemented by the development of refined mouse models of human cancers for use in genetic screens and functional genomic studies. Some areas of research include:
Cancer genomics and epigenomics. In addition to array-based comparative genomic hybridization (CGH) technology, Next-generation sequencing technologies are utilized to characterize mouse and human cancer genomes. As a data generation center of TCGA, the team is responsible for generating low-pass whole-genome sequencing data for copy number and structural arrangements. As a data analysis center, in collaboration with colleagues at the Broad Institute, the group is actively developing analytical pipelines for TCGA data processing and analyses. In addition to developing systematic approaches to integrate data across species (e.g., comparison of mouse and human tumors) 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 development in order to further expand our view of the oncogenome with increasing accuracy and sensitivity.
Functional genomics. Beyond generation and gathering of genomic data, our goal is to rapidly functionalize such data for translation into the clinic. Based on the integration of genomic data with developmental or cancer biological insights, we are performing genome-wide RNAi screens and focused gain-of-function genetic screens using in vitro and in vivo model systems. These studies are allowing us to quickly and efficiently apply a functional filter to genomic datasets and thus identify the most promising cancer-relevant genes for detailed mechanistic studies.
System biology. Leveraging genomic technology, computational network modeling and genetically engineered mouse models, there is increasing emphasis on system biology studies to understand complex signaling/pathways in metastasis and therapeutic responses/resistance.
Genetics and biology of metastasis. One of the major areas of emphasis in our functional genomics program is metastasis. 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; (2) identifying progression drivers that are keys to enabling dissemination to distal organ sites and investigating the molecular mechanisms mediating melanoma metastasis.
Tumor microenvironment. Leveraging human tissues, mouse models, and genomic technology, there is a focus effort in characterizing and exploiting the tumor microenvironment in understanding progression, therapeutic response and resistance.
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.
Kim MJ, Gans J, Nogueira CN, Wang A, Paik JH, Feng B, Brennan C, Hahn W, Cordon-Cardo C, Wagner SN, Flotte T, Duncan L, Granter SR and Chin L. Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Cell, 2006. 125, 1269-1281.
The Cancer Genome Atlas Research Network "Comprehensive genomic characterization defines human glioblastoma genes and core pathways." Nature AOP 5 Sept 2008. #Corresponding authors: Chin L and Meyerson M. PMID: 18772890
Scott KL, Kabbarah O, Liang M-C, Ivanova E, Anagnostou V, Wu J, Dhakal S, Wu M, Chen S, Feinberg T, Huang J, Saci A, Widlund HR, Fisher DE, Xiao YH, Rimm DL, Protopopov A, Wong KK, Chin L. GOLPH3 modulates mTOR signaling and sensitivity in rapamycin in cancer. Nature 2009; 459(7250):1085-90. PMID: 19553991
Scott KL, Nogueira C, Heffernan TP, van Doorn R, Dhakal S, Hanna JA, Min C, Jaskelioff M, Xiao YH, Wu C-J, Cameron LA, Perry SR, Zeid R, Feinberg R, Kim MJ, Vande Woude G, Granter SR, Bosenberg M, Chu GC, DePinho RA, Rimm DL and Chin L. Pro-invasion metastasis drivers in early stage melanoma are oncogenes. Cancer Cell 2011; 20(1):92-103. PMID: 21741599
Ding Z, Wu CJ, Jaskelioff M, Ivanova E, Kost-Alimova M, Protopopov A, Chu GC, Wang G, Lu X, Labrot ES, Hu J, Wang W, Xiao Y, Zhang H, Zhang J, Zhang J, Gan B, Perry SR, Jiang S, Li L, Homer JW, Wang YA, Chin L, DePinho RA. Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases. Cell. 2012 [Epub ahead of print] PMID: 22341455
Berger MF, Hodis E, Heffernan TP, Lissanu-Deribe Y, Lawrence MS, Protopopov A, Ivanova E, Watson IR, Nickerson E, Ghosh P, Zhang H, Zeid R, Ren X, Cibulskis K, Sivachenko AY, Wagle N, Sucker A, Sougnez C, Onofrio R, Ambrogio L, Auclair D, Fennell T, Carter SL, Drier Y, Stojanov P, Singer MA, Voet D, Jing R, Saksena G, Barretina J, Ramos AH, Pugh TJ, Parkin M, Winckler W, Mahan S, Ardlie K, Baldwin J, Wargo J, Schadendorf D, Meyerson M, Gabriel SB, Golub TR, Wagner SN, Lander ES, Getz G, Chin L#, Garraway LA# (# = co-corresponding authors) Melanoma genome sequencing reveals frequent PREX2 mutations. Nature (in press)