Victor Velculescu, M.D., Ph.D.
Associate Professor of Oncology
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Room 5M05, Cancer Research Building
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It is now widely accepted that cancer is a genetic disease mediated by alterations in specific genes. However, many of the key suppressor genes and oncogenes responsible for cancer initiation and progression remain to be identified. Our laboratory is focused on developing and applying genome-wide approaches for identification of molecular differences between human cancer cells and normal cells. These alterations can exist at the level of the genome, involving mutations of specific genes underlying tumorigenesis, or at the level of the transcriptome, involving differential expression of genes in cancer cells. Using genomic tools we have developed over the past several years, including high throughput sequencing approaches, serial analysis of gene expression (SAGE), and a novel method called Digital Karyotyping, we have begun to elucidate the genetic and gene expression differences important in neoplasia. Future work will focus on systematically using these technologies to identify previously undiscovered oncogenes and suppressor genes involved in colorectal cancer. The identification of such genetic alterations will provide insight into the pathogenesis of cancer and open up new possibilities for diagnostic and therapeutic intervention.
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- Velculescu V.E., Madden S.L., Zhang L., Lash A.E., Yu J., Rago C., Lal A., Wang C.J., Beaudry G.A., Ciriello K.M., Cook B.P., Dufault M.R., Ferguson A.T., Gao Y., He T.C., Hermeking H., Hiraldo S.K., Hwang P.M., Lopez M.A., Luderer H.F., Mathews B., Petroziello J.M., Polyak K., Zawel L., Zhang W., Zhang X., Zhou W., Haluska F.G., Jen J., Sukumar S., Landes G.M., Riggins G.J., Vogelstein B., Kinzler K.W. Analysis of human transcriptomes. Nature Genetics 23: 387-8, 1999.
- Saha S, Sparks AB, Rago C, Akmaev V, Wang CJ, Vogelstein B, Kinzler KW, Velculescu VE. Using the transcriptome to annotate the genome. Nature Biotechnology 20:508-12, 2002.
- Wang TL, Maierhofer C, Speicher MR, Lengauer C, Vogelstein B, Kinzler KW, Velculescu VE. Digital karyotyping. Proceedings of the National Academy of Sciences, USA 99:16156-16161, 2002
- Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S, Saha S, Markowitz S, Willson JK, Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE. Mutational analysis of the tyrosine kinome. Science 300:949, 2003
- Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE. High frequency of mutations of the PIK3CA gene in human cancers. Science 304: 554, 2004.
- Wang Z, Shen D, Parsons DW, Bardelli A, Sager J, Szabo S, Ptak J, Silliman N, Peters BA, Van Der Heijden MS, Parmigiani G, Yan H, Wang TL, Riggins G, Powell SM, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE. Mutational analysis of the tyrosine phosphatome in colorectal cancers. Science 304:1164-6, 2004.
- Samuels Y, Diaz LA Jr, Schmidt-Kittler O, Cummins JM, Delong L, Cheong I, Rago C, Huso DL, Lengauer C, Kinzler KW, Vogelstein B, Velculescu VE. Mutant PIK3CA promotes cell growth and invasion of human cancer cells. Cancer Cell 7(6):561-73, 2005.
- Parsons DW, Wang TL, Samuels Y, Bardelli A, Cummins JM, DeLong L, Silliman N, Ptak J, Szabo S, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Lengauer C, Velculescu VE. Colorectal cancer: mutations in a signalling pathway. Nature 436(7052):792, 2005.
- Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber T, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE. The Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science. 314(5797):268-74, 2006.