D. Joseph Jerry

Professor of Veterinary and Animal Sciences, University of Massachusetts

Email: jjerry@vasci.umass.edu
J. Jerry Vet & Animal Sciences Web Site
J. Jerry PVLSI Web Site

Ph.D.: Pennsylvania State University
Postdoctoral Training: Jackson Laboratory; Baylor College of Medicine

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.

Representative publications:

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.

Dunphy, K.A., Blackburn, A.C., Yan, H., OConnell, L.R., and Jerry, D.J. 2008. Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice. Br. Cancer Res. 12;10(3):R43.

Bappaditya Samanta, Haoheng Yan, Nicholas O. Fischer, Jing Shi, D. Joseph Jerry, Vincent M. Rotello. 2008. Protein-passivated Fe3O4 nanoparticles: low toxicity and rapid heating for thermal therapy. J. Materials Chem. 18:1204-1206 Cover image.

Koch, J.G., Gu, X.., Han, Y., El-Naggar, A.K., Olson, M.V., Medina, D., Jerry, D.J., Blackburn, A.C., Peltz, G., Amos, C.I., and Lozano, G. 2007.  Mammary tumor modifiers in BALB/cJ mice heterozygous for p53. Mamm. Genome 18(5):300-9.

Jerry, D.J. 2007. Roles for estrogen and progesterone in breast cancer prevention. Br. Cancer Res. 9(2):102. (Invited editorial)

Blackburn, A.C., Hill, L.Z., Roberts, A.L., Wang, J., Aud, D., Jung, J., Nikolcheva, T., Allard, J., Peltz, G. Otis, C.N., Cao, Q. J., Ricketts, R. St. J., Naber, S.P., Mollenhauer, J., Poustka, A., Malamud, D., and Jerry, D.J. 2007. Genetic mapping in mice identifies DMBT1 as a candidate modifier of breast cancer risk. Am. J. Pathol. 170:2030-41.

Tu, Yifan, Jerry, D.J., Pazik, B. And Schneider, S.S. 2005. Sensitivity to DNA damage is a common component of hormone based strategies for protection of the mammary gland. Mol. Cancer Res. 3:435-442.

Becker, K.A., Lu, S.L., Dickinson, E.S., Dunphy, K.A., Mathews, L., Schneider, S.S. and Jerry, D.J. 2005. Estrogen and progesterone regulate radiation-induced p53 activity through TGF-? dependent pathways. Oncogene 24:6345-6353.

Blackburn, A.C., McLary, S.C., Naeem, R., Luszcz, J., Stockton, D.W., Donehower, L.A., Mohammed, M., Mailhes, J.B., Soferr, T., Naber, S.P., Otis, C.N., and Jerry, D.J. 2004. Loss of heterozygosity occurs via mitotic recombination in Trp53+/- mice and associates with mammary tumor susceptibility of the BALB/c strain. Cancer Res. 64:5140-5147.

Blackburn, A.C., Brown, J.S., Naber, S.P., Otis, C.N. Wood, J.T., and Jerry, D.J. 2003. BALB/c alleles for Prkdc and Cdkn2a interact to modify tumor susceptibility in Trp53+/- mice. Cancer Res. 63:2364-2368, 2003.

Minter L.M., Kuperwasser C.K., Dickinson E.S., and D.J. Jerry (2002) Cell-cycling status of mammary epithelial cells predicts p53 responsiveness to gamma-radiation. Development 129:2997-3008. Pub Med Abstract

Jerry D.J., Minter L.M., Becker K.A., and A.C. Blackburn (2002) Hormonal control of p53 and chemoprevention. Br. Cancer Res. 4:91-94. PubMed Abstract

Poothapillai K, Knott J.G., Wang Z., Jerry D. J., and J.M. Robl (2001) Production of calves from G1 fibroblasts. Nat. Biotechn. 19:1176-1178. PubMed Abstract

Kuperwasser C., Hurlbut G.D., Kittrell F.S., Medina D., Dickinson E.S., Naber S.P. and D.J. Jerry (2000) Development of spontaneous mammary tumors in BALB/c p53-heterozygous mice: A model for Li-Fraumeni syndrome. Am. J. Pathol. 157:2151-2159. PubMed Abstract

Kuperwasser C., Pinkas J., Hurlbut G.D., Naber S.P., and D.J. Jerry (2000) Cytoplasmic sequestration and functional repression of p53 in mammary epithelium is reversed by hormonal treatment. Cancer Res. 60:2723-2729. PubMed Abstract

Jerry D.J., Kittrell F.S., Kuperwasser C., Laucirica R., Dickinson E.S., Bonilla P.J., Butel J.S., and D. Medina (2000) A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development. Oncogene 19:1052-1058. PubMed Abstract

Pinkas J., Butel J.S., Medina D. and D.J. Jerry (1999) Alternative splicing of the p53-binding domain in mdm2 during mammary tumorigenesis in the mouse. Int. J. Cancer 81:292-298. PubMed Abstract

Jerry D.J., Kuperwasser C., Downing S., Pinkas J., He C., Dickinson E.S., Marconi S., and S.P. Naber (1998) Delayed involution of the mammary epithelium in BALB/c-p53null mice. Oncogene 17:2305-2312. PubMed Abstract