Last Updated: 3/28/2007

Terry A Van Dyke, Ph.D. Professor Cancer Genetics

Research Interests
The central goal of the lab is to study and understand the mechanisms of cancer development at many levels, including genetic, molecular, cell and systems biology. Because cancer can develop in over 100 distinct mammalian cell types, and it does so amidst complex cell-cell and cell-environment interactions, we have utilized genetically engineered mice (GEM) as the foundation for our analyses. We have established several preclincal cancer models that have facilitated analyses of the tumor suppressors, p53, pRb, and PTEN, among others, including their contribution to normal growth control and the consequences of their inactivation to multi-step tumorigenesis. This approach enables a detailed examination of the molecular and cellular events in developing tumors - studies that are not possible in humans. We couple in vivo approaches with in vitro primary cell culture approaches to refine our discoveries. Projects in the Van Dyke lab have elucidated mechanisms of aberrant proliferation, apoptosis and migration of cancer cells of multiple lineages in vivo. Studies are underway to characterize the chromosomal and gene expression aberrations that characterize these events. Furthermore, mechanisms of angiogenesis and invasiveness are being explored. In the process of these mechanistic studies, we have developed highly penetrant preclinical models for cancers of breast, prostate, and choroid plexus epithelia, as well as high-grade astrocytoma. These models are also being used to develop live animal imaging approaches to both characterize the disease process and to monitor preclinical therapeutic testing. Thus, the Lab utilizes a "tool box" full of modern technologies to approach the complexities of this aggressive and devastating disease.

Recent Accomplishments and Honors
Editorial Board, The Cancer Journal: The Journal of Principles & Practice of Oncology. 2007
Organizer, Keystone Conference, Mouse Models at the Frontiers of Cancer Discovery 2007
Organizer, 30th Annual Lineberger Symposium, Mouse Models of Human Cancer at the Edge of Discovery 2006
Organizer, Mouse Models of Cancer Symposium, AACR Annual Meeting 2004
Organizer, AACR Special Meeting; Mouse Models of Cancer 2003
Editorial Boards: Cancer Research, Molecular Cancer Research, International Journal of Oncology, Cancer Cell, Carcinogenesis, MCB
ASCB Annual Meeting Symposium Chair - 2002
Mouse Models of Human Cancer Consortium Co-Chair 1999 - 2002
Gordon Conference (Cancer), Chair - 1997
AACR Annual Meeting Symposium Chair - 1997

Training
1981 Ph.D. Medical Sciences; University of Florida, Gainesville

1982-1986 Postdoctoral Research Fellow with Dr. Arnold J. Levine, Microbiology Department, SUNY, Stony Brook and Department of Molecular Biology, Princeton University

Publications

Wu, M. Wade, L. Krall, J. Grisham, Y. Xiong and T. Van Dyke (1996) Targeted in vivo Expression of the Cdk Inhibitor, p21, Halts Hepatocyte Cell Cycle Progression, Postnatal Liver Development and Regeneration, Genes and Development, 10:245.

Bowman, T., Symonds, H., Gu, L., Oren, M., and T. Van Dyke (1996) Tissue-Specific Inactivation of p53 Tumor Suppression in the Mouse, Genes and Development, 10:826-835.

Yin, C., Knudson, M., Korsmeyer, S., and Van Dyke, T., (1997) Bax Suppresses Tumorogenesis and Stimulates Apoptosis in vivo, Nature, 385:637-640

Liao, X. X. Zhang, R. Hill, J. Gao, M. B. Qumsiyeh, W. Nichols, and T. Van Dyke. (1998) No Requirement for V(D)J Recombination in p53-Deficient Thymic Lymphoma. Mol. Cell. Biol. 18: 3495-3501

Pan H, Yin C, Yamaskai L. Dyson N, Harlow E, and Van Dyke T. (1998) Key roles for E2F1 in p53-dependent apoptosis and cell cycle regulation within developing tumors. Molecular Cell. 2:283-292.

Liao M-J, Yin C, Barlow C, Wynshaw-Boris A, and Van Dyke T. (1999) Atm is dispensable for p53 apoptosis and tumor suppression triggered by cell cycle dysfunction. Mol. Cell. Biol. 19: 3095-3102.

Liao M-J and Van Dyke TA. (1999) Critical role for Atm in suppressing VDJ recombination-driven thymic lymphoma. Genes and Development, in press.

Salganik RI, Albright CD, Rodgers J, Kim J, Zeisel SH, Sivanshenskiy MS, and Van Dyke TA. (2000)
Antioxidant depletion: Enhancement of apoptotic tumor cell death and inhibition of brain tumor
growth in transgenic mice. Carcinogenesis, 21:909-914.

Lu, X., G. Magrane, D.N.Louis, J. Gray, and T. Van Dyke. (2001) Selective inactivation of p53 facilitates mouse epithelial tumor Progression without Chromosomal Instability. Mol. and Cell. Biol.,21:6017-6030.

Garciduenas L., Alcaraz, A., Salazar G., Tascareno A., Garcia R., Osnaya N., Calderon A., Devlin R.
and Van Dyke TA. (2001) Nasal Biopsies of Children Exposed to Air Polluntants. Toxicologic
Pathology, 29:558-564.

Tolbert D, Lu X, Yin C, Tantama, M and VanDyke TA. (2002) p19ARF is Dispensible for oncogenic
stress-Induced p53-dependent Apoptosis and Tumor Suppression in vivo. Mol. and Cell. Biol.,
22:370-377.

Perkins EJ, Nair A, Cowley DO, Van Dyke T. Chang Y., Ramsden DA. (2002) Sensing of Intermediates
in V(D)J recombination by ATM. Genes and Dev. 16:159-64.

Xiao A, Wu H, Louis DN, Pandolfi PP, Van Dyke TA. (2002) Astrocyte inactivation of the pRb pathway
predisposes mice to malignant astrocytoma development that is accelerated by PTEN Mutation.
Cancer Cell. 1:157-68.

Weiss, W A, Israel M., Cobbs C., Holland E., James C D, Louis D N, Marks Cheryl, McClatchey A., Roberts T., Van Dyke T. Wetmore C., Chiu I., Giovannini M., Guha A., Higgins R., Marino S.,
Radovanovic I., Reilly K., Aldape K.(2002) Neuropathology of genetically engineered mice.
Oncogene. 21;44

Trotman, L., Niki, M., Dotan,Z., Koutcher, J., Di Cristofano, A, Xiao, A, Khoo, A., Roy-Burman, Greenberg, N. , Van Dyke, T., Cordon-Cardo, C. P.P Pandolfi. (2003) Pten Dose Dictates Cancer Progression in the Prostate. PloS Biology, PloS Biology, 1: 385-396.

Simin, K. H. Wu, L. Lu, D. Pinkel, D. Albertson, R. Cardiff, and Van Dyke TA (2004) pRb Inactivation in Mammary Cells Predisposes to Adenocarcinoma and Reveals Common Mechanisms for Tumor Initiation and Progression in Divergent Epithelia. PloS Biology, 2:194-205.

Albright, C.D., Salganik, R.I., and Van Dyke TA (2004) Dietary Depletion of Vitamin E and Vitamin A Inhibits Mammary Tumor Growth and Metastasis in Transgenic Mice. Journal of Nutrition, in press.

Nister, M., Beeche, M., Zhang, X-Q., Yin, C., Hu, X., Tang, M., Enblad, G., Van Dyke, T., and Wahl, G.M. (2005) p53 must be competent for transcriptional regulation to suppress tumor formation. Oncogene 24, 3563-3573

Van Dyke, T (2005) Cancer biology: sense out of missense. Nature 17;434(7031):287-8. (invited review)

Li, Chengwen, Bowles, D., R. Jude Samulski, and Terry Van Dyke (2005) Adeno-associated virus vectors: potential applications for cancer gene therapy. Cancer Gene Therapy.

Xiao, A, C. Yin, C. Yang, A. Di Cristofano, P. Pandolfi and T. Van Dyke (2005) Somatic Induction of Pten Loss in a Preclinical Astrocytoma Model Reveals Major Roles in Disease Progression and Avenues for Target Discovery and Validation, Cancer Research. 2005 Jun 15; 65(12):5172-80. (Cover story)

Brubaker, L. M., E. Bullitt, C. Yin, T. Van Dyke, W. Lin. (2005) Magnetic resonance angiography visualization of abnormal tumor vasculature in genetically engineered mice. Cancer Research. Sep 15;65(18):8218-23. 2005.

Cowley, D., G. Muse and Van Dyke, T. (2005) A Dominant Interfering Bub1 Mutant is Insufficient to Induce or Alter Tumorigenesis In Vivo, Even in a Sensitized Genetic Background. Mol. Cell. Bio. Sept; 25(17):7796-7802.

Hill, R., Y. Song, R. D. Cardiff, and T. Van Dyke (2005) Heterogeneous Tumor Evolution Initiated by Loss of pRb Function in a preclinical Prostate Cancer Model. Cancer Research. Nov 15;65(22):10243-54.

Hill, R., Y. Song, R.D. Cardiff, and T. Van Dyke (2005) Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis. Cell. Dec 16; 123(6):1001-11. (Cover story)

Elizabeth Bullitt1, P. Anne Wolthousen2 , Lauren Brubaker3, Weili Lin3, Donglin Zeng4 and Terry Van Dyke2. (2006) Malignancy-Associated Vessel Tortuosity: A Computer-Assisted, MRA Study of Choroid Plexus Carcinoma in Genetically Engineered Mice. American Journal of Neuroradiology 27(3):612-9.

Gutmann DH, Maher EA, Van Dyke T. (2006) Mouse Models of Human Cancers Consortium Workshop on Nervous System Tumors. Cancer Res. 66(1):10-3.

K. Simin, R. Hill, Y. Song, Q. Zhang, R. Bash, R.D. Cardiff, C. Yin, A. Xiao, K. McCarthy, T. Van Dyke (2006) Deciphering Cancer Complexities in Genetically Engineered Mice In Cold Spring Harbor Symposia on Quantitative Biology LXX , 2008;70:283-90.

McLear, Julie A., German Garcia-Fresco, Manzoor A. Bhat and Terry A. Van Dyke (2006) In Vivo Inactivation of pRb, p107 and p130 in Murine Neuroprogenitor Cells Leads to Major CNS Developmental Defects Culminating in High Seizure Rates. Mol. Cell. Neurosciences, 33:260-273. (cover article)

Terry A. Van Dyke (2007) p53 and Tumor Suppression. N Engl J Med 356;1.

Bullitt, E., Stephen R Aylward, Terry Van Dyke, and Weili Lin (2007) Computer-Assisted Measurement of Vessel Shape from 3T Magnetic Resonance Angiography of Mouse Brain, Methods, in press.

Submitted or In Preparation:
Cowley, D., J. Rivera-Perez, T. Oliver, L. Lu, R. O’Quinn, E.D. Salmon, T. Magnuson and T. Van Dyke (2007) Mitotic Regulator Aurora-A Kinase: Essential Role in Bipolar Spindle Formation and in Early Development, submitted.

Lu, Xiangdong, Chunyu Yang , M. Christine Hollander, Albert J. Fornace Jr. and Terry Van Dyke (2007) Inactivation of gadd45a gene sensitizes brain epithelial tumors to radiation treatment in vivo. (submitted)

Zhang, Q., Yang, C.Y., McCarthy, K.D., Jacks, T., Louis, D.N., T. Van Dyke (2007) Inducible etiology of high
Grade astrocytic tumors in genetically programmed mice: Mechanistic insight and a path to preclinical
development. (submitted)

Herschkowitz, J.I*, Simin, K*, Weigman, V.J., Mikaelian, I., Hu, Z., Rasmussen, K., Chandrasekharan, S., Backlund, M.G., Glazer, R.I., Yuzhi, Y., Brown, P.H., Green, J. E., Kopelovich, L., Churchill, G .A., Van Dyke, T., Perou, C. M. (2007) Comparison of Murine and Human Mammary Tumors using DNA Microarrays. *These authors contributed equally to this work. (submitted)

Cowley, D., M. Schliekelman, T. Oliver, R. O’Quinn, E.D. Salmon, and T. Van Dyke (2007) Mitotic Regulator Bub 1: A Murine Allelic Series, in preparation.

Zhang L, Allan R, Wu H, and Van Dyke TA (2007) Highly penetrant diabetes induced by targeted expression of cell cycle inhibitors in liver and pancreas (in preparation).

Lu, Xiangdong, Chunyu Yang, Chaoying, Yin, Terry Van Dyke (2007) p53-mediated apoptosis provides the selective pressure for p53 inactivation in carcinoma progression. (in preparation)

Li, Chengwen, Chaoyin Ying, Hongyan Zhao, R. Jude Samulski and Terry Van Dyke (2007) Antiangiogenic Therapy of Tumor with Adeno-Associated Virus Serotype 1 Vectors Encoding Murine Endostatin and Angiostatin. (in preparation)

Yin, C., and Van Dyke, T. (2007) Progression to angiogenesis coincident with somatic inactivation of p53 in a transgenic brain tumor model. (in preparation)

Zhang, Q, T. Jacks and T. Van Dyke (2007) Physiological CNS induction of activated K-Ras perturbs neural precursor differentiation along the rostral migratory stream and predisposes to glioblastoma. (in preparation)

Fogarty, A., Zhang, L and T. Van Dyke (2007) Transgenic expression of Arf in pancreatic islets induces diabetes dependent on p53 function. (in preparation)

E-mail: tvdlab@med.unc.edu
Telephone: (919) 962-2145 / 2148
FAX: (919) 843-3160
Address: 12-044 LCCC, CB# 7295 Chapel Hill, NC 27599
URL: cancer.med.unc.edu/vandykelab/

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