Research Interests: 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 the disease. These observations emphasize the important contributions of both genetic background and hormonal exposures in determining the risk of 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 the p53 protein are responsive to hormonal stimuli and vary across different stages of mammary gland development. Therefore, a major focus of the laboratory is to discover the normal cellular mechanisms that regulate p53 function and determine whether sustained elevation in p53 activity may prevent mammary tumors. We also use genetic mapping strategies in mice to identify low-penetrance modifiers of mammary tumor susceptibility. 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 a cellular basis for susceptibility to breast cancer.
In addition, we are identifying the genetic signature for women with atypical hyperplasia of the breast, who are at highest risk for developing breast cancer. There is an immediate need for this type of diagnostic tool, as routine mammography produces approximately 286,000 biopsy diagnosed cases of atypia in the United States, each year. Of these women, approximately 54,000 will go on to develop breast cancer. However, oncologists are currently unable to identify these high-risk women, who should receive some sort of preventative/interventional therapy. Instead, they are prescribed "watchful waiting."
Rays of Hope Center for Breast Cancer Research (Co-Director)
Center of Excellence in Apoptosis Research
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 KA, Blackburn AC, Yan H, O'Connell LR, Jerry DJ. Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice. Br Cancer Res. 2008;10(3):R43.
Samanta B, Yan H, Fischer NO, Shi J, Jerry DJ, et al. Protein-passivated Fe3O4 nanoparticles: low toxicity and rapid heating for thermal therapy. J Materials Chem. 2008;18:1204-1206.
Koch JG, Gu X, Han Y, El-Naggar A, Medina D, Jerry DJ, et al. Mammary tumor modifiers in BALB/cJ mice heterozygous for p53. Mamm Genome. 2007;18(5):300-309.
Blackburn AC, Hill LZ, Roberts AL, Wang J, Aud D, Jung J, Nikolcheva T, Allard J, Peltz G, Otis CN, Cao QJ, Ricketts R, Naber SP, Mollenhauer J, Poustka A, Malamud D, Jerry DJ. Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk. Am J Pathol. 2007;170:2030-2041.
Becker KA, Lu SL, Dickinson ES, Dunphy KA, Mathews L, Schneider SS, Jerry DJ. Estrogen and progesterone regulate radiation-induced p53 activity through TGF-β dependent pathways. Oncogene. 2005;24:6345-6353.
Blackburn AC, McLary SC, Naeem R, Luszcz J, Stockton DW, Donehower LA, Mohammed M, Mailhes JB, Soferr T, Naber SP, Otis CN, Jerry DJ. Loss of heterozygosity occurs via mitotic recombination in Trp53+/- mice and associates with mammary tumor susceptibility of the BALB/c strain. Cancer Res. 2004;64:5140-5147.
Blackburn AC, Brown JS, Naber SP, Otis CN, Wood JT, Jerry DJ. BALB/c alleles for Prkdc and Cdkn2a interact to modify tumor susceptibility in Trp53+/- mice. Cancer Res. 2003;63:2364-2368.
Minter LM, Dickinson ES, Naber SP, Jerry DJ. Epithelial cell cycling predicts p53 responsiveness to g-irradiation during post-natal mammary gland development. Development. 2002;129:2997-3008.
Jerry DJ, Kittrell FS, Kuperwasser C, et al. A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development. Oncogene. 2000;19:1052-1058.
Kuperwasser C, Hurlbut GD, Kittrell FS, Medina D, Dickinson ES, Naber SP, Jerry DJ. Development of spontaneous mammary tumors in BALB/c p53-heterozygous mice: a model for Li-Fraumeni syndrome. Am J Pathol. 2000;157:2151-2159.
Jerry DJ, Kuperwasser C, Downing S, et al. Delayed involution of the mammary epithelium in BALB/c-p53null mice. Oncogene. 1998;17:2305-2312.
Milestone Award for 5th Patent, University of Massachusetts Amherst