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Structural and Computational Biology and Molecular Biophysics

Houston, Texas

A BCM research lab.
Structural and Computational Biology & Molecular Biophysics
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Lynda Chin, M.D.

Professor and Chair, Department of Genomic Medicine

Scientific Director, Institute for Applied Cancer Science

University of Texas M.D. Anderson Cancer Center

Education:

B.S., Brown University, 1988
M.D., Albert Einstein College of Medicine, 1993
Internship, Columbia Presbyterian Medical Center, 1994
Residency, Albert Einstein College of Medicine, 1997

Research Interests:

My research program focuses on the molecular biology and (epi) genetics/(epi) genomics of cancer gensis, maintenance, and progression in multiple tumor types, with strong emphasis on translation to enable the practice of genomic medicine. Major effects to characterize the oncogenome in humans and mice are complemented by the development of refined mouse and human cell models of human cancers, functional genomics studies, and computational modeling to address important questions in a systems biology manner. Some areas of research include:

Cancer genomics and epigenomics
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 rearrangements. 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 indentify 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. Areas of interest include epigenomic profiling to understand the DNA promoter methylation, chromatin modification, and higher order structure.

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 targeted functional genomic screens using RNAi and cDNA ORFs in a context-specific manner. 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 engineering mouse models, there is increasing emphasis on system biology studies to understand complex signaling/pathways in metastasis and therapeutic responses/resistance, with an interest in development of co-extinction strategies.

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 metastic 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.

Selected Publications:

  • Kwong, L.N, Costello, J.C., Liu, H., Genovese, G., Jiang, S., Jeong, J.H., Bender, R.P., Collins, J.J., and Chin, L. RAS acts as a multi-state rheostat to differentially regulate survival and proliferation in cancer. Nature Medicine, (2012).
  • Hodis, E., Watson, I.R., Kryukov, G.V., Arold, S.T., Imielinski, M., Cibulskis, K., Sivachenko, A., Voet, D., Saksena, G., Stransky, N., Onofrio, R.C., Winckler, W., Ardlie, K., Wagle, N., Wargo, J., Chong, K., Morton, D.L., Stemke-Hale, K., Chen, G., Noble, M., Meyerson, M., Ladbury, J.E., Davies, M.A., Gershenwald, J.E., Wagner, S.N., Hoon, D.S., Schadendorf, D., Lander, E.S., Gabriel, S.B., Getz, G., Garraway, L.A.*, and Chin, L.* (*co-corresponding authors). A landscape of driver mutations in melanoma. Cell, 150:251-263, (2012). PubMed
  • Genovese, G., Ergun, A., Shukla, S.A., Campos, B., Hanna, J., Ghosh, P., Quayle, S.N., Rai, K., Colla, S., Ying, H., Wu, C.J., Sarkar, S., Xiao, Y., Zhang, J., Zhang, H., Kwong, L., Dunn, K., Wiedemeyer, W.R., Brennan, C., Zheng, H., Rimm, D.L., Collins, J.J., and Chin, L. microRNA regulatory network inference identifies miR-34a as a novel regulator of TGF beta signaling in GBM. Cancer Discov., [Epub ahead of print], 2012. PubMed
  • Berger, M.F., Hodis, E., Heffernan, T.P., Lissanu-Deribe, Y., Lawrence, M.S., Alexei Protopopov, A., Ivanova, E., Watson, I.R., Nickerson, E., Ghosh, P., Zhang, H., Zeid, R., Ren, X., Cibulskis, K., Sivachenko, A.Y., Wagle, N., Sucker, A., Sougnez, C., Onofrio, R., Ambrogio, L., Auclair, D., Fennell, T., Carter, S.L., Drier, Y., Stojanov, P., Singer, M.A., Voet, D., Jing, R., Saksena, G., Barretina, J., Ramos, A.H., Pugh, T.J., Parkin, M., Winckler, W., Mahan, S., Ardlie, K., Baldwin, J., Wargo, J., Schadendorf, D., Meyerson, M., Gabriel, S.B., Golub, T.R., Wagner, S.N., Lander, E.S., Getz, G., Chin, L.*, and Garraway, L.A.* (*co-corresponding authors). Melanoma genome sequencing reveals frequent PREX2 mutations. Nature, 485:502-506, (2012). PubMed
  • Ding, Z., Wu, C.J., Jaskelioff, M., Ivanova, E., Kost-Alimova, M., Protopopov, A., Chu, G.C., Wang, G., Lu, X., Labrot, E.S., Hu, J., Wang, W., Xiao, Y., Zhang, H., Zhang, J., Gan, B., Perry, S.R., Jiang, S., Li, L, Horner, J.W., Wang, Y.A., Chin, L.*, and DePinho, R.A.* (*co-corresponding authors). Telemorase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases. Cell, 148:896-907, (2012). PubMed
  • Scott, K.L., Nogueira, C., Heffernan, T.P., van Doorn, R., Dhakal, S., Hanna, J.A., Min, C., Jaskelioff, M., Xiao, Y.H., Wu, C-J, Cameron, L.A., Perry, S.R., Zeid, R., Feinberg, R., Kim, M.J., Vande Woude, G., Granter, S.R., Bosenberg, M., Chu, G.C., DePinho, R.A., Rimm, D.L., and Chin, L. Pro-invasion metastasis drivers in early stage melanoma are oncogenes. Cancer Cell, 20:92-103, (2011). PubMed
  • Scott, K.L, Kabbarah, O., Liang, M-C, Ivanova, E., Anagnostou, V., Wu, J., Dhakal, S., Wu, M., Chen, S., Feinberg, T., Huang, J., Saci, A., Widlund, H.R., Fisher, D.E., Xiao, Y.H., Rimm, D.L., Protopopov, A., Wong, K.K., and Chin, L. GOLPH3 modulates mTOR signaling and sensitivity to rapamycin in cancer. Nature, 459:1085-1090, (2009). PubMed

For more publications, see listing on PubMed.

Contact Information:

Department: Genomic Medicine
Address: 1901 East Road
Houston, TX 77054
Phone: 713-792-6876
Fax: 713-792-6870
E-mail: lchin@mdanderson.org
Additional Links: Executive Assistant: Debra Shears-Green, dshears@mdanderson.org

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