Department Affiliation: Oncology
Degree: Ph.D., Johns Hopkins University
Rank: Professor
Telephone Number: 410-955-2928
Fax Number: 410-955-0548
E-mail: kinzlke@jhmi.edu
School of Medicine Address: Room 588, Cancer Research Bldg., 1650 Orleans Street, Baltimore, MD 21231
Molecular genetics of human cancer
Our laboratory is devoted to understanding the genetic changes that underlie the development of human cancer. Our efforts are largely focused on colorectal cancer which is the second leading cause of cancer deaths in the United States. Colorectal tumorigenesis proceeds through several well recognized clinical and histopathological stages ranging from small benign tumors to metastatic carcinoma. This progression is associated with a series of genetic changes affecting at least one oncogene and several tumor suppressor genes. Additionally, two autosomal dominantly inherited predispositions to colon cancer, Familial Adenomatous Polyposis (FAP) and Hereditary Non-Polyposis Colon Cancer (HNPCC), have been described. We have identified numerous mutated genes that underlie sporadic and inherited forms of colon cancer. Current research efforts are focused on 3 areas, (i) systematic searches for additional mutated genes in human cancer, (ii) delineation of the biochemical sequelae of these genetic alterations, and (iii) exploitation of these alterations for the early diagnosis and treatment of cancer.
Representative Publications:
- Morin, P.J., Sparks, A.B., Korinek, V., Barker, N., Clevers, H., Vogelstein, B., and Kinzler, K.W. Activation of b-catenin/Tcf signaling in colon cancer by mutations in b-catenin or APC, Science 275:1787-1790, 1997. Pub Med Reference
- Zhang, L., Zhou, W., Velculescu, V.E., Kern, S.E., Hruban, R.H., Hamilton, S.R., Vogelstein, B., and Kinzler, K.W. Gene expression profiles in normal and cancer cells, Science 276:1268-1272, 1997. Pub Med Reference
- He, T-C., Sparks, A.B., Rago, C., Hermeking, H., Zawel, L., da Costa, L.T., Morin, P.J., Vogelstein, B., and Kinzler, K.W. Identification of c-MYC as a target of the APC pathway, Science 281:1509-1512, 1998. Pub Med Reference
- He, T.-C., Chan, T.A., Vogelstein, B., and Kinzler, K.W. PPARdelta is an APC-regulated targetof nonsteroidal anti-inflammatory drugs, Cell 99:335-345, 1999. Pub Med Reference
- Torrance, C.J., Agrawal, V., Vogelstein, B., and Kinzler, K.W. Use of isogenic human cancer cells for high-throughput screening and drug discovery, Nature Biotechnology 19:940-945, 2001. Pub Med Reference
- Chan, T.A., Wang, Z., Dang, L.H., Vogelstein, B. and Kinzler, K.W. Targeted inactivation of CTNNB1 reveals unexpected effects of b-catenin mutation, Proc. Natl. Acad. Sci. USA 99:8265-8270, 2002. Pub Med Reference
- Yan, H., Yuan, W., Velculescu, V.E., Vogelstein, B. and Kinzler, K.W. Allelic variation in human gene expression, Science 297:1143, 2002. Pub Med Reference
- Wang, Z., Vogelstein, B. and Kinzler, K.W. Phosphorylation of Beta-catenin at S33, or T41 can occur in the absence of phosphorylation at T45 in colon cancer cells, Cancer Research 63:5234-5235, 2003. Pub Med Reference
- Samuels, Y., Wang, Z., Bardelli, A., Silliman, N., Ptak, J., Szabo, S., Yan, H., Gazdar, A., Powell, S.M., Riggins, G.J., Willson, J.K., Markowitz, S., Kinzler, K.W., Vogelstein, B. and Velculescu, V.E. High frequency of mutations of the PIK3CA gene in human cancers, Science 304:554, 2004. Pub Med Reference
- Vogelstein, B. and Kinzler, K.W. Cancer genes and the pathways they control, Nature Medicine 10:789-799, 2004. Pub Med Reference
- Peters, B.A., Diaz, L.A., Polyak, K., Meszler, L., Romans, K., Guinan, E.C., Antin, J.H., Myerson, D., Hamilton, S.R., Vogelstein, B., Kinzler, K.W. and Lengauer C. Contribution of bone marrow-derived endothelial cells to human tumor vasculature, Nature Medicine 3:261-262, 2005. Pub Med Reference
- Diehl, F., Li, M., Dressman, D., He, Y., Shen, D., Szabo, S., Diaz, L.A. Jr., Goodman, S.N., David, K.A., Juhl, H., Kinzler, K.W. and Vogelstein, B. Detection and quantification of mutations in the plasma of patients with colorectal tumors, Proc. Natl. Acad. Sci. USA 102:16968-16373, 2005. Pub Med Reference
- Sjöblom, T., Jones, S., Wood, L.D., Parsons, D.W., Lin, J., Barber, T., Mandelker, D., Leary, R.J., Ptak, J., Silliman, N., Szabo, S., Buckhaults, P., Farrell, C., Meeh, P., Markowitz, S.D., Willis, J., Dawson, D., Willson, J.K.V., Gazdar, A.F., Hartigan, J., Wu, L., Liu, C., Parmigiani, G., Park, B.H., Bachman, K.E., Papadopoulos, N., Vogelstein, B., Kinzler, K.W. and Velculescu, V.E. The Consensus Coding Sequences of Human Breast and Colorectal Cancers. Science 314: 268-274, 2006. Pub Med Reference
- Wood, L.D., Leary, R,J., Shen, D., Boca, S.M., Barber, T., Ptak, J., Silliman, N., Szabo, S., Dezso, Z., Ustyanksky, V., Nikolskaya, T., Nikolsky, T., Karchin, R., Wilson, P.A., Kaminker, J.A., Zhang, Z., Croshaw, R., Willis, J., Dawson, D., Shipitsin, M., Willson, J.K.V., Sukumar, S., Polyak, K., Park, B.H., Pethiyagoda, C.L., Pant, P.V.K., Ballinger, D.G., Sparks, A.B., Hartigan, J., Smith, D. R., Suh, E., Papadopoulos, N., Buckhaults, P., Markowitz,S.D., Parmigiani, G., Kinzler, K.W., Velculescu, V.E. and Vogelstein, B. The genomic landscapes of human breast and colorectal cancers. Science 318: 1108-1113, 2007. Pub Med Reference
Other graduate programs in which Dr. Kinzler participates:
Anti-Cancer Drug Development Program
Program in Human Genetics
