Cancer Genomics

Cancer is a genetic disease caused by mutations in individual cells which cause them to no longer be governed by normal processes of growth and death within the organism. At Cold Spring Harbor we are focusing on many aspects of cancer. Our lab focuses on the genetic variants involving the progression of cancer. In doing this we have looked at a number of different types of cancer to better understand the process by which after cancer is initiated, the cancer cells grow and become metastatic. Recently we are focusing on how we can improve the resolution with which we understand the cancer genome. We are doing this with a combination of using long-read sequencing and the analysis of single cells. The long-term goal of this research is to identify steps within this process can be attacked with drugs to treat the cancer.

Selected Publications:

Streppel, M. M. and Lata, S. and Delabastide, M. and Montgomery, E. A. and Wang, J. S. and Canto, M. I. and Macgregor-Das, A. M. and Pai, S. and Morsink, F. H. and Offerhaus, G. J. and Antoniou, E. and Maitra, A. and McCombie, W. R. (2014) Next-generation sequencing of endoscopic biopsies identifies ARID1A as a tumor-suppressor gene in Barrett’s esophagus. Oncogene, 33(3) pp. 347-57.

Navin, N. E. and Kendall, J. T. and Troge, J. E. and Andrews, P. and Rodgers, L. and McIndoo, J. and Cook, K. and Stepansky, A. and Levy, D. and Esposito, D. and Muthuswamy, L. and Krasnitz, A. and McCombie, W. R. and Hicks, J. B. and Wigler, M. H. (2011) Tumour evolution inferred by single-cell sequencing. Nature, 472(7341) pp. 90-94.

Bric, A. and Miething, C. and Bialucha, C. U. and Scuoppo, C. and Zender, L. and Krasnitz, A. and Xuan, Z. and Zuber, J. and Wigler, M. H. and Hicks, J. B. and McCombie, W. R. and Hemann, M. T. and Hannon, G. J. and Powers, S. and Lowe, S. W. (2009) Functional identification of tumor-suppressor genes through an in vivo RNA interference screen in a mouse lymphoma model. Cancer Cell, 16(4) pp. 324-35.

Zender, L. and Xue, W. and Zuber, J. and Semighini, C. P. and Krasnitz, A. and Ma, B. and Zender, P. and Kubicka, S. and Luk, J. M. and Schirmacher, P. and McCombie, W. R. and Wigler, M. H. and Hicks, J. B. and Hannon, G. J. and Powers, S. and Lowe, S. W. (2008) An Oncogenomics-Based In Vivo RNAi Screen Identifies Tumor Suppressors in Liver Cancer. Cell, 135(5) pp. 852-864.

Burgess, D. J. and Doles, J. and Zender, L. and Xue, W. and Ma, B. and McCombie, W. R. and Hannon, G. J. and Lowe, S. W. and Hemann, M. T. (2008) Topoisomerase levels determine chemotherapy response in vitro and in vivo. Proc Natl Acad Sci U S A, 105(25) pp. 9053-9058.

Mu, D. and Chen, L. Y. and Zhang, X. P. and See, L. H. and Koch, C. M. and Yen, C. and Tong, J. J. and Spiegel, L. and Nguyen, K. C. Q. and Servoss, A. and Peng, Y. and Pei, L. and Marks, J. R. and Lowe, S. W. and Hoey, T. and Jan, L. Y. and McCombie, W. R. and Wigler, M. H. and Powers, S. (2003) Genomic amplification and oncogenic properties of the KCNK9 potassium channel gene. Cancer Cell, 3(3) pp. 297-302.

Soengas, M. S. and Capodieci, P. and Polsky, D. and Mora, J. and Esteller, M. and Opitz-Araya, X. and McCombie, R. and Herman, J. G. and Gerald, W. L. and Lazebnik, Y. A. and Cordon-Cardo, C. and Lowe, S. W. (2001) Inactivation of the apoptosis effector Apaf-1 in malignant melanoma. Nature, 409(6817) pp. 207-211.

Li, J. and Yen, C. and Liaw, D. and Podsypanina, K. and Bose, S. and Wang, S. I. and Puc, J. and Miliaresis, C. and Rodgers, L. and McCombie, R. and Bigner, S. H. and Giovanella, B. C. and Ittmann, M. and Tycko, B. and Hibshoosh, H. and Wigler, M. H. and Parsons, R. (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science, 275(5308) pp. 1943-7.