D. Joseph Jerry

Professor

Phone: 413-545-5335
Fax: 413-545-6326
Email: jjerry@vasci.umass.edu
Classes:
Ansci 672: Molecular Medicine (spring)
Ansci 511: Advanced Genetics (alternate years)

M.S.: Purdue University
Ph.D.: The Pennsylvania State University
Postdoctoral Training:
Jackson Laboratory, Bar Harbor, Maine
Baylor College of Medicine, Houston, Texas

Research Interests

• Regulation of the p53 tumor susceptibility gene and susceptibility to breast cancer.
• Methods for genetic modification of livestock.

Tumor Suppressor Genes and the Cellular Basis for Susceptibility to Breast Cancer

Reproductive factors and family history of breast cancer are the most important predictors of an individual’s risk of developing breast cancer. These observations emphasize the important contributions of both genetic background and hormonal exposures in determining the risk of breast cancer. Mutations in tumor suppressor genes (TP53, BRCA1, BRCA2) render the breast epithelium at increased risk of forming tumors. These genes have pivotal roles in sensing DNA damage and ensuring appropriate cellular responses. Hormones that stimulate proliferation and direct breast development have also been shown to increase risk of breast cancer. However, hormonal exposures accompanying a single full-term pregnancy diminishes lifetime risk of breast cancer by half. It is the goal of our laboratory to define the molecular pathways that mediate susceptibility and resistance to breast cancer and design targeted therapeutics to prevent breast cancer.

Our laboratory has demonstrated an association between activity of the p53 tumor suppressor protein and incidence of mammary tumors. Expression and activity of p53 protein is responsive to hormonal stimuli and varies across different stages of mammary gland development. Therefore, a major focus of the laboratory is to discover the normal cellular mechanisms that regulate p53 expression and function and determine whether sustained elevation in p53 activity may prevent mammary tumors. Genetically engineered mice bearing targeted disruption of tumor suppressor genes and conditional overexpression of oncogenes are being used to identify factors that regulate p53 function. Genetic mapping strategies are also being used to identify low-penetrance modifiers of mammary tumor susceptibility that differ between strains of mice. Genes that regulate p53 function would provide novel targets for prevention and treatment of breast cancer. Through the use of contemporary techniques in molecular and cellular biology with animal models, we are defining the developmental biology of the breast epithelium itself, while providing both a genetic and cellular basis for susceptibility to breast cancer.

The mechanisms by which tumor suppressor genes regulate cancer susceptibility are important to numerous cellular processes. These genes arbitrate decisions of whether cells live or die in response to stress stimuli. They also interact with basic cellular machinery that ensures integrity of genomic DNA. These activities can be modulated to improve the efficiency of genetic modification in somatic cells. These approaches together with nuclear transplantation will make it possible to create genetically engineered animals to produce biomedical compounds and cell-based therapeutics.

Selected Publications

Lu, S., Becker, K.A., Hagen, M.J., Yan, H., Roberts, A.L., Mathews, L.A., Schneider, S.S., Siegelmann, H.T., Tirrell, S.M., MacBeth, K.J., Blanchard, J.L. and Jerry, D.J. 2008. Transcriptional responses to estrogen and progesterone in Mammary gland identify networks regulating p53 activity. Endocrinology. (E-pub on June 12)

Dunphy, K.A., Blackburn, A.C., Yan, H., O’Connell, 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.

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

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

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

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

Reviews and Textbooks

Blackburn A.C. and D.J. Jerry (2002) The use of animal models to study the role of the p53 tumor suppressor in breast cancer. Br. Cancer Res. 4:101-111 PubMed Abstract

Jerry D.J., Dickinson E.S., and A.L. Roberts (2002) Regulation of apoptosis during mammary involution by the p53 tumor suppressor gene. J. Dairy Sci. 85:1103-1110. PubMed Abstract

Jerry D.J. and M.A. Ozbun (2002) TP53 tumor suppressor gene: structure and function. In: Encyclopedia of Cancer, 2nd Edition. Editor: Joseph Bertino. Academic Press, San Diego, California, Volume 4, pages 415-431.

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