Ph.D., Columbia University, 1978
Human genetic disorders; population genetics; cancer genomics
Our laboratory has for many years studied the molecular basis of cancer, in particular the genetic mutations that drive the evolution of the cancer cell. In recent years this has been extended to the study of the genetic mutations that underlie devastating genetic diseases such as congenital heart disease and autism. Common to both areas are a set of genome technologies for measuring copy number variation between cells. With this technique, the entire genome of the cell can be scanned at very high resolution (Lucito et al., 2003), and changes in gene copy numbers resulting from deletions and amplifications can be readily detected. We are applying these methods to a large set of clinically annotated breast and ovarian cancers, making correlations with clinical outcome, and discovering new disease causing genes. The same technique has application in the analysis of spontaneous mutations in the germ-line. Hence, we are applying the methodology to finding the lesions causing sporadic genetic disease. The laboratory has a particularly intense need for bioinformatics and algorithmic interpretation from genome-wide experimental data.
Sebat, J., Lakshmi, B., Malhotra, D., Troge, J., Lese-Martin, C., Walsh, T., Yamrom, B., Yoon, S., Krasnitz, A., Kendall, J., Leotta, A., Pai, D., Zhang, R., Lee, Y-H., Hicks, J., Spence, S.J., Lee, A.T., Puura, K., Lehtimäki, T., Ledbetter, D., Gregersen, P.K., Bregman, J., Sutcliffe, J.S., Jobanputra, V., Chung, W., Warburton, D., King, M-C., Skuse, D., Geschwind, D.H., Gilliam, T.C., Ye, K., and Wigler, M. 2007. Strong association of de novo copy number mutations with autism. Science 316: 445–449.
Pelham, R.J., Rodgers, L., Hall, I., Lucito, R., Nquyen, K.C.Q., Navin, N., Hicks, J., Mu, D., Powers, S., Wigler, M., and Botstein, M. 2006. Identification of alterations in DNA copy number in host stromal cells during tumor progression. Proc. Natl. Acad. Sci. USA 103: 19848–19853.
Hicks, J., Krasnitz, A., Lakshmi, B., Navin, N.E., Riggs, M., Leibu, E., Esposito, D., Alexander, J., Troge, J., Grubor,V., Yoon, S., Wigler, M., Ye, K., Børresen-Dale, A-L., Naume, B., Schlicting, E., Norton, L., Hagerstrom, T., Skoog, L., Auer, G., Maner, S., Lundin, P., and Zetterberg, A. 2006. Novel patterns of genomic rearrangement and their association with survival in breast cancer. Genome Res. 16: 1465–1479.
Sebat, J., Lakshmi, B., Troge, J., Alexander, J., Young, J., Lundin, P., Maner, S., Massa, S., Walker, M., Chi, M., Navin, N., Lucito, R., Healy, J., Hicks, J., Ye, K., Reiner, A., Gilliam, T.C., Trask, B., Patterson, N., Zetterberg, A., and Wigler, M. 2003. Large-scale copy number polymorphism in the human genome. Science 305: 525–528.
Lucito, R., Healy, J., Alexander, J., Reiner, A., Esposito, D., Chi, M., Rodgers, L., Brady, A., Sebat, J., Troge, J., West, J., Rostan, S., Nguyen, K.C.Q., Powers, S., Ye, K.Q., Olshen, A., Venkatraman, E., Norton, L., and Wigler, M. 2003. Microarray analysis of genome copy number variation. Genome Res. 13: 2291–2305.