We have utilized genetic, molecular, and cell biological approaches to explore the molecular pathways utilized by these tumor suppressors. These studies have identified some components of the pathway(s) and have shown which of them may or may not act as tumor suppressors, and why. This type of analysis provides validation of mechanisms suggested by in vitro studies, and in addition can reveal previously unknown possibilities. Also under study are the genes and mechanisms involved in tumor progression in each model. Genetic studies of predictable tumor stages form the basis for these projects. For example, in the brain model, loss of the normal p53 allele occurs predictably in all in animals of a p53+/- background, modeling what happens in human cancer. Subsequent to p53 loss, these tumors rapidly progress to highly aggressive states, including extensive angiogenesis and invasiveness. This enables a detailed examination of the molecular and cellular events in developing tumors, a study not possible in human cancers. Studies are underway to determine the chromosomal and gene expression aberrations that characterize these events. Finally, tissue-specific genetic knock-out technology is being applied to the systematic analysis of tumor-specific functions. Reduction of p53-dependent apoptosis in tumor progression.
RECENT PUBLICATIONS:
Johnson CE, Huang YY, Parrish AB, Smith MI, Vaughn AE, Zhang Q, Wright KM, Van Dyke T, Wechsler-Reya RJ, Kornbluth S, Deshmukh M. Differential Apaf-1 levels allow cytochrome c to induce apoptosis in brain tumors but not in normal neural tissues. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20820-5. Epub 2007
Wu Z, Sun J, Zhang T, Yin C, Yin F, Van Dyke T, Samulski RJ, Monahan PE. Optimization of Self-complementary AAV Vectors for Liver-directed Expression Results in Sustained Correction of Hemophilia B at Low Vector Dose. Mol Ther. Epub 2007
Bullitt E, Aylward SR, Van Dyke T, Lin W. Computer-assisted measurement of vessel shape from 3T magnetic resonance angiography of mouse brain. Methods. 2007 Sep;43(1):29-34
Der CJ, Van Dyke T. Stopping ras in its tracks. Cell. 2007 Jun 1;129(5):855-7
Herrmann JM, Bernardo J, Long HJ, Seetoo K, McMenamin ME, Batista EL Jr, Van Dyke TE, Simons ER. Sequential chemotactic and phagocytic activation of human polymorphonuclear neutrophils. Infect Immun. 2007 Aug;75(8):3989-98. Epub 2007
Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, Hu Z, Rasmussen KE, Jones LP, Assefnia S, Chandrasekharan S, Backlund MG, Yin Y, Khramtsov AI, Bastein R, Quackenbush J, Glazer RI, Brown PH, Green JE, Kopelovich L, Furth PA, Palazzo JP, Olopade OI, Bernard PS, Churchill GA, Van Dyke T, Perou CM. Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol. 2007;8(5):R76.
Chai J, Lu X, Godfrey V, Fletcher C, Roberts CW, Van Dyke T, Weissman BE. Tumor-specific cooperation of retinoblastoma protein family and Snf5 inactivation. Cancer Res. 2007 Apr 1;67(7):3002-9
Van Dyke T. p53 and tumor suppression. N Engl J Med. 2007 Jan 4;356(1):79-81
McLear JA, Garcia-Fresco G, Bhat MA, Van Dyke TA. In vivo inactivation of pRb, p107 and p130 in murine neuroprogenitor cells leads to major CNS developmental defects and high seizure rates. Mol Cell Neurosci. 2006 Nov;33(3):260-73. Epub 2006
Dietrich T, Kaye EK, Nunn ME, Van Dyke T, Garcia RI. Gingivitis susceptibility and its relation to periodontitis in men. J Dent Res. 2006 Dec;85(12):1134-7
Simin K, Hill R, Song Y, Zhang Q, Bash R, Cardiff RD, Yin C, Xiao A, McCarthy K, van Dyke T. Deciphering cancer complexities in genetically engineered mice. Cold Spring Harb Symp Quant Biol. 2005;70:283-90
Bullitt E, Wolthusen PA, Brubaker L, Lin W, Zeng D, Van Dyke T. Malignancy-associated vessel tortuosity: a computer-assisted, MR angiographic study of choroid plexus carcinoma in genetically engineered mice. AJNR Am J Neuroradiol. 2006 Mar;27(3):612-9
Dillon S, Agrawal S, Banerjee K, Letterio J, Denning TL, Oswald-Richter K, Kasprowicz DJ, Kellar K, Pare J, van Dyke T, Ziegler S, Unutmaz D, Pulendran B. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance.
Gutmann DH, Maher EA, Van Dyke T. Mouse Models of Human Cancers Consortium Workshop on Nervous System Tumors. Cancer Res. 2006 Jan 1;66(1):10-3
Biochemistry and Biophysics - UNC School of Medicine
