|D. Joseph Jerry
Professor of Veterinary and Animal Sciences, University of Massachusetts
Ph.D.: Pennsylvania State University
Tumor Suppressor Genes and the Cellular Basis for Susceptibility to Breast Cancer
Loss of specific tumor suppressor genes has been demonstrated in both familial and sporadic breast cancers; however, the underlying genetic and cellular basis of susceptibility in breast tissue is poorly understood. Critical phases of breast development have been identified during which susceptibility to breast cancer is increased. In contrast, the differentiation of the breast epithelium that takes place during a single full-term pregnancy diminishes life-time risk of breast cancer by half. It is the goal of my laboratory to define the molecular events that regulate susceptibility of the breast epithelium and develop strategies to intervene in these pathways.
We have observed changes in the expression and function of the p53 tumor suppressor gene in breast tissues at different stages of development. Therefore, a major focus of the laboratory is to discover the normal cellular mechanisms that regulate p53 expression and function. A variety of mammary epithelial cell lines and mice bearing knockout alleles or transgenes are used in studies to identify factors that regulate p53 activities in apoptosis, cell cycle arrest, and suppression of tumors. More recently, we have begun to look at epigenetic changes in tumor cells that can be reversed by nuclear transplantation. Through the combined use of transgenic animals and contemporary techniques in molecular and cellular biology, we are defining the developmental biology of the breast epithelium itself, while providing both a genetic and cellular basis for susceptibility to breast cancer.
Nguyen DH, Oketch HA, Illa-Bochaca I, Geyer FC, Reis-Filho JS, Mao JH, Ravani SA, Zavadil J, Borowsky AD, Jerry DJ, et al. Radiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease breast cancer latency and affect tumor type. Cancer Cell. In press.
Blackburn AC, Jerry DJ. Map making in the 21st century: charting breast cancer susceptibility pathways in rodent models. J. Mammary Gland Biol Neoplasia. In press. doi:10.1007.
Tao L, Roberts AL, Dunphy KA, Bigelow C, Yan H, Jerry DJ. Repression of mammary stem/progenitor cells by p53 is mediated by notch and separable from apoptotic activity. Stem Cells. 2011;29:119-127.
Cellurale C, Weston CR, Reilly J, Garlick DE, Jerry DJ, et al. Role of JNK in a Trp53-dependent mouse model of breast cancer. PLoS One. 2010;305(8):e12469.
Jerry DJ, Griner NB, Tao L. Tumor suppressor pathways and cellular origins of breast cancer: new complexities and new hopes. NanoLife. 2010;1:1-16.
Bajaj A, Oscar M, Phillips R, Kim IB, Jerry DJ, et al. Array based sensing of normal, cancerous and metastatic cells using conjugated fluorescent polymers. J Am Chem Soc. 2010;32(3):1018-1022.
Yan H, Blackburn AC, McLary SC, Tao L, Dickinson ES, Roberts AL, Naber SP, Otis CN, Cao QJ, Lawlor RG, Osborne BA, Kittrell FS, Medina D, Jerry DJ. Multiple pathways contribute to development of spontaneous mammary tumors in BALB/c-Trp53+/- mice. Am J Pathol. 2010;176(3):1421-1432.
Jerry DJ, Dunphy KA, Hagen MJ. Estrogens, regulation of p53 and breast cancer risk: a balancing act. Cell Mol Life Sci. 2010;67(7):1017-1023.
Troester MA, Lee MH, Carter M, Fan C, Pirone JR, Perou CM, Jerry DJ, et al. Activation of host wound responses in breast cancer microenvironment. Clin Cancer Res. 2009;15(22):7020-7028.
Tchatchou S, Lyer S, Schmutzhard J, Freidekind O, Gronert S, Mietag C, D'Amato M, Hemminki K, Sutter C, Wappenschmidt B, Blackburn AC, Hill LZ, Jerry DJ, et al. Identification of DMBT1 alleles associated with increased breast cancer risk and altered function. Hum Mol Genet. 2009;31(1):60-66.
Bajaj A, Miranda O, Kim I-K, Philips R, Jerry DJ, et al. Detection and differentiation of normal, cancerous, and metastatic cells using nanoparticle-polymer sensor arrays. Proc Natl Acad Sci USA. 2009;106(27):10912-10916.
Bajaj A, Samanta B, Yan H, Jerry DJ, et al. Stability, toxicity and differential cellular uptake of protein passivated-Fe3O4 nanoparticles. J Mater Chem. 2009;(19):6328-6331.
Lu S, Becker KA, Hagen MJ, Yan H, Roberts AL, Mathews LA, Schneider SS, Siegelmann HT, Tirrell SM, MacBeth KJ, Blanchard JL, Jerry DJ. Transcriptional responses to estrogen and progesterone in mammary gland identify regulatory networks associated with p53 activity. Endocrinology. 2008;149(10):4809-4820.