D. Joseph Jerry

D. Joseph Jerry

Professor

Science Director, Pioneer Valley Life Sciences Institute
Co-Director, Rays of Hope Center for Breast Cancer Research

Photo of D. Joseph Jerry

Office phone: 413-545-5335

Fax: 413-545-6326

Email: jjerry [at] vasci [dot] umass [dot] edu

Office location: 427P ISB

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

Classes:
ANIML SCI  672: Molecular Medicine (spring, alternate years)
  

 

  • 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.

Sturgeon SR, Arcaro KF, Johnson MA, Balasubramanian R, Zorn M, Jerry JD, Schneider SS.  2014.  DNA methylation in paired breast epithelial and white blood cells from women undergoing reduction mammoplasty.. Anticancer Res. 34(6):2985-90.
Böhringer M, Obermeier K, Griner N, Waldraff D, Dickinson E, Eirich K, Schindler D, Hagen M, Jerry DJ, Wiesmüller L.  2013.  siRNA screening identifies differences in the Fanconi anemia pathway in BALB/c-Trp53+/- with susceptibility versus C57BL/6-Trp53+/- mice with resistance to mammary tumors.. Oncogene.
Yadava N, Schneider SS, Jerry JD, Kim C.  2013.  Impaired mitochondrial metabolism and mammary carcinogenesis.. J Mammary Gland Biol Neoplasia. 18(1):75-87.
Petrocca F, Altschuler G, Tan SM, Mendillo ML, Yan H, Jerry JD, Kung AL, Hide W, Ince TA, Lieberman J.  2013.  A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells.. Cancer Cell. 24(2):182-96.
Dunphy KA, Seo J-H, Kim DJ, Roberts AL, Tao L, Direnzo J, Balboni AL, Crisi GM, Hagen MJ, Chandrasekaran T et al..  2013.  Oncogenic transformation of mammary epithelial cells by transforming growth factor beta independent of mammary stem cell regulation.. Cancer Cell Int. 13(1):74.
Compton S, Kim C, Griner NB, Potluri P, Scheffler IE, Sen S, Jerry JD, Schneider S, Yadava N.  2011.  Mitochondrial dysfunction impairs tumor suppressor p53 expression/function.. J Biol Chem. 286(23):20297-312.
Tao L, Roberts AL, Dunphy KA, Bigelow C, Yan H, Jerry JD.  2011.  Repression of mammary stem/progenitor cells by p53 is mediated by Notch and separable from apoptotic activity.. Stem cells (Dayton, Ohio). 29(1):119-27.
Dunphy KA, Schneyer AL, Hagen MJ, Jerry JD.  2011.  The role of activin in mammary gland development and oncogenesis.. Journal of mammary gland biology and neoplasia. 16(2):117-26.
Nguyen DH, Oketch-Rabah HA, Illa-Bochaca I, Geyer FC, Reis-Filho JS, Mao J-H, Ravani SA, Zavadil J, Borowsky AD, Jerry JD et al..  2011.  Radiation acts on the microenvironment to affect breast carcinogenesis by distinct mechanisms that decrease cancer latency and affect tumor type.. Cancer cell. 19(5):640-51.
Dunphy KA, Schneyer AL, Hagen MJ, Jerry JD.  2011.  The role of activin in mammary gland development and oncogenesis.. J Mammary Gland Biol Neoplasia. 16(2):117-26.
Cellurale C, Weston CR, Reilly J, Garlick DS, Jerry JD, Sluss HK, Davis RJ.  2010.  Role of JNK in a Trp53-dependent mouse model of breast cancer.. PLoS One. 5(8):e12469.
Bajaj A, Miranda OR, Phillips R, Kim I-B, Jerry JD, Bunz UHF, Rotello VM.  2010.  Array-based sensing of normal, cancerous, and metastatic cells using conjugated fluorescent polymers.. J Am Chem Soc. 132(3):1018-22.
Jerry JD, Dunphy KA, Hagen MJ.  2010.  Estrogens, regulation of p53 and breast cancer risk: a balancing act.. Cellular and molecular life sciences : CMLS. 67(7):1017-23.
Yan H, Blackburn AC, McLary CS, Tao L, Roberts AL, Xavier EA, Dickinson ES, Seo JH, Arenas RB, Otis CN et al..  2010.  Pathways contributing to development of spontaneous mammary tumors in BALB/c-Trp53+/- mice.. Am J Pathol. 176(3):1421-32.
Jerry JD, Dunphy KA, Hagen MJ.  2010.  Estrogens, regulation of p53 and breast cancer risk: a balancing act.. Cell Mol Life Sci. 67(7):1017-23.
Dunphy KA, Tao L, Jerry JD.  2010.  Mammary epithelial transplant procedure.. Journal of visualized experiments : JoVE. (40)
Tchatchou S, Riedel A, Lyer S, Schmutzhard J, Strobel-Freidekind O, Gronert-Sum S, Mietag C, D'Amato M, Schlehe B, Hemminki K et al..  2010.  Identification of a DMBT1 polymorphism associated with increased breast cancer risk and decreased promoter activity.. Hum Mutat. 31(1):60-6.
Yan H, Blackburn AC, McLary CS, Tao L, Roberts AL, Xavier EA, Dickinson ES, Seo JH, Arenas RB, Otis CN et al..  2010.  Pathways contributing to development of spontaneous mammary tumors in BALB/c-Trp53+/- mice.. The American journal of pathology. 176(3):1421-32.
Bajaj A, Miranda OR, Phillips R, Kim I-B, Jerry JD, Bunz UHF, Rotello VM.  2010.  Array-based sensing of normal, cancerous, and metastatic cells using conjugated fluorescent polymers.. Journal of the American Chemical Society. 132(3):1018-22.
Bajaj A, Miranda OR, Kim I-B, Phillips RL, Jerry JD, Bunz UHF, Rotello VM.  2009.  Detection and differentiation of normal, cancerous, and metastatic cells using nanoparticle-polymer sensor arrays.. Proceedings of the National Academy of Sciences of the United States of America. 106(27):10912-6.
Roy R, Jerry JD, Thayumanavan S.  2009.  Virus-inspired approach to nonviral gene delivery vehicles.. Biomacromolecules. 10(8):2189-93.
Troester MA, Lee MH, Carter M, Fan C, Cowan DW, Perez ER, Pirone JR, Perou CM, Jerry JD, Schneider SS.  2009.  Activation of host wound responses in breast cancer microenvironment.. Clin Cancer Res. 15(22):7020-8.
Roy R, Jerry JD, Thayumanavan S.  2009.  Virus-inspired approach to nonviral gene delivery vehicles.. Biomacromolecules. 10(8):2189-93.
Bajaj A, Miranda OR, Kim I-B, Phillips RL, Jerry JD, Bunz UHF, Rotello VM.  2009.  Detection and differentiation of normal, cancerous, and metastatic cells using nanoparticle-polymer sensor arrays.. Proc Natl Acad Sci U S A. 106(27):10912-6.
Jerry JD, Tao L, Yan H.  2008.  Regulation of cancer stem cells by p53.. Breast cancer research : BCR. 10(4):304.
Lu S, Becker KA, Hagen MJ, Yan H, Roberts AL, Mathews LA, Schneider SS, Siegelmann HT, MacBeth KJ, Tirrell SM et al..  2008.  Transcriptional responses to estrogen and progesterone in mammary gland identify networks regulating p53 activity.. Endocrinology. 149(10):4809-20.
Dunphy KA, Blackburn AC, Yan H, O'Connell LR, Jerry JD.  2008.  Estrogen and progesterone induce persistent increases in p53-dependent apoptosis and suppress mammary tumors in BALB/c-Trp53+/- mice.. Breast cancer research : BCR. 10(3):R43.
Lu S, Becker KA, Hagen MJ, Yan H, Roberts AL, Mathews LA, Schneider SS, Siegelmann HT, MacBeth KJ, Tirrell SM et al..  2008.  Transcriptional responses to estrogen and progesterone in mammary gland identify networks regulating p53 activity.. Endocrinology. 149(10):4809-20.
Jerry JD, Tao L, Yan H.  2008.  Regulation of cancer stem cells by p53.. Breast Cancer Res. 10(4):304.
Samanta B, Yan H, Fischer NO, Shi J, Jerry JD, Rotello VM.  2008.  Protein-passivated Fe(3)O(4) nanoparticles: low toxicity and rapid heating for thermal therapy.. J Mater Chem. 18(11):1204-1208.
Blackburn AC, Hill LZ, Roberts AL, Wang J, Aud D, Jung J, Nikolcheva T, Allard J, Peltz G, Otis CN et al..  2007.  Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk.. Am J Pathol. 170(6):2030-41.
Blackburn AC, Hill LZ, Roberts AL, Wang J, Aud D, Jung J, Nikolcheva T, Allard J, Peltz G, Otis CN et al..  2007.  Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk.. The American journal of pathology. 170(6):2030-41.
Koch JG, Gu X, Han Y, El-Naggar AK, Olson MV, Medina D, Jerry JD, Blackburn AC, Peltz G, Amos CI et al..  2007.  Mammary tumor modifiers in BALB/cJ mice heterozygous for p53.. Mamm Genome. 18(5):300-9.
Becker KA, Lu S, Dickinson ES, Dunphy KA, Mathews L, Schneider SS, Jerry JD.  2005.  Estrogen and progesterone regulate radiation-induced p53 activity in mammary epithelium through TGF-beta-dependent pathways.. Oncogene. 24(42):6345-53.
Becker KA, Lu S, Dickinson ES, Dunphy KA, Mathews L, Schneider SS, Jerry JD.  2005.  Estrogen and progesterone regulate radiation-induced p53 activity in mammary epithelium through TGF-beta-dependent pathways.. Oncogene. 24(42):6345-53.
Tu Y, Jerry JD, Pazik B, Schneider SS.  2005.  Sensitivity to DNA damage is a common component of hormone-based strategies for protection of the mammary gland.. Molecular cancer research : MCR. 3(8):435-42.
Blackburn AC, McLary CS, Naeem R, Luszcz J, Stockton DW, Donehower LA, Mohammed M, Mailhes JB, Soferr T, Naber SP et al..  2004.  Loss of heterozygosity occurs via mitotic recombination in Trp53+/- mice and associates with mammary tumor susceptibility of the BALB/c strain.. Cancer research. 64(15):5140-7.
Blackburn AC, McLary CS, Naeem R, Luszcz J, Stockton DW, Donehower LA, Mohammed M, Mailhes JB, Soferr T, Naber SP et al..  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(15):5140-7.
Blackburn AC, Brown JS, Naber SP, Otis CN, Wood JT, Jerry JD.  2003.  BALB/c alleles for Prkdc and Cdkn2a interact to modify tumor susceptibility in Trp53+/- mice.. Cancer Res. 63(10):2364-8.
Blackburn AC, Brown JS, Naber SP, Otis CN, Wood JT, Jerry JD.  2003.  BALB/c alleles for Prkdc and Cdkn2a interact to modify tumor susceptibility in Trp53+/- mice.. Cancer research. 63(10):2364-8.
Blackburn AC, Jerry JD.  2002.  Knockout and transgenic mice of Trp53: what have we learned about p53 in breast cancer? Breast cancer research : BCR. 4(3):101-11.
Jerry JD, Minter LM, Becker KA, Blackburn AC.  2002.  Hormonal control of p53 and chemoprevention.. Breast cancer research : BCR. 4(3):91-4.
Jerry JD, Minter LM, Becker KA, Blackburn AC.  2002.  Hormonal control of p53 and chemoprevention.. Breast Cancer Res. 4(3):91-4.
Jerry DJ, Dickinson ES, Roberts AL, Said TK.  2002.  Regulation of apoptosis during mammary involution by the p53 tumor suppressor gene.. J Dairy Sci. 85(5):1103-10.
Minter LM, Dickinson ES, Naber SP, Jerry JD.  2002.  Epithelial cell cycling predicts p53 responsiveness to gamma-irradiation during post-natal mammary gland development.. Development (Cambridge, England). 129(12):2997-3008.
Jerry DJ, Dickinson ES, Roberts AL, Said TK.  2002.  Regulation of apoptosis during mammary involution by the p53 tumor suppressor gene.. Journal of dairy science. 85(5):1103-10.
Kasinathan P, Knott JG, Moreira PN, Burnside AS, Jerry DJ, Robl JM.  2001.  Effect of fibroblast donor cell age and cell cycle on development of bovine nuclear transfer embryos in vitro.. Biology of reproduction. 64(5):1487-93.
Kasinathan P, Knott JG, Wang Z, Jerry DJ, Robl JM.  2001.  Production of calves from G1 fibroblasts.. Nat Biotechnol. 19(12):1176-8.
Kasinathan P, Knott JG, Wang Z, Jerry DJ, Robl JM.  2001.  Production of calves from G1 fibroblasts.. Nature biotechnology. 19(12):1176-8.
Kuperwasser C, Hurlbut GD, Kittrell FS, Dickinson ES, Laucirica R, Medina D, Naber SP, Jerry DJ.  2000.  Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice. A model for Li-Fraumeni syndrome.. The American journal of pathology. 157(6):2151-9.
Jerry DJ, Kittrell FS, Kuperwasser C, Laucirica R, Dickinson ES, Bonilla PJ, Butel JS, Medina D.  2000.  A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development.. Oncogene. 19(8):1052-8.
Kuperwasser C, Pinkas J, Hurlbut GD, Naber SP, Jerry DJ.  2000.  Cytoplasmic sequestration and functional repression of p53 in the mammary epithelium is reversed by hormonal treatment.. Cancer research. 60(10):2723-9.
Jerry DJ, Kittrell FS, Kuperwasser C, Laucirica R, Dickinson ES, Bonilla PJ, Butel JS, Medina D.  2000.  A mammary-specific model demonstrates the role of the p53 tumor suppressor gene in tumor development.. Oncogene. 19(8):1052-8.
Kuperwasser C, Hurlbut GD, Kittrell FS, Dickinson ES, Laucirica R, Medina D, Naber SP, Jerry DJ.  2000.  Development of spontaneous mammary tumors in BALB/c p53 heterozygous mice. A model for Li-Fraumeni syndrome.. Am J Pathol. 157(6):2151-9.
Pinkas J, Naber SP, Butel JS, Medina D, Jerry DJ.  1999.  Expression of MDM2 during mammary tumorigenesis.. International journal of cancer. Journal international du cancer. 81(2):292-8.
Jerry DJ, Pinkas J, Kuperwasser C, Dickinson ES, Naber SP.  1999.  Regulation of p53 and its targets during involution of the mammary gland.. Journal of mammary gland biology and neoplasia. 4(2):177-81.
Pinkas J, Naber SP, Butel JS, Medina D, Jerry DJ.  1999.  Expression of MDM2 during mammary tumorigenesis.. Int J Cancer. 81(2):292-8.
Jerry DJ, Pinkas J, Kuperwasser C, Dickinson ES, Naber SP.  1999.  Regulation of p53 and its targets during involution of the mammary gland.. J Mammary Gland Biol Neoplasia. 4(2):177-81.
Medina D, Stephens LC, Bonilla PJ, Hollmann CA, Schwahn D, Kuperwasser C, Jerry DJ, Butel JS, Meyn RE.  1998.  Radiation-induced tumorigenesis in preneoplastic mouse mammary glands in vivo: significance of p53 status and apoptosis.. Mol Carcinog. 22(3):199-207.
Jerry DJ, Kuperwasser C, Downing SR, Pinkas J, He C, Dickinson E, Marconi S, Naber SP.  1998.  Delayed involution of the mammary epithelium in BALB/c-p53null mice.. Oncogene. 17(18):2305-12.
Zawada WM, Cibelli JB, Choi PK, Clarkson ED, Golueke PJ, Witta SE, Bell KP, Kane J, Ponce de Leon FA, Jerry DJ et al..  1998.  Somatic cell cloned transgenic bovine neurons for transplantation in parkinsonian rats.. Nat Med. 4(5):569-74.
Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, Ponce de León FA, Robl JM.  1998.  Cloned transgenic calves produced from nonquiescent fetal fibroblasts.. Science. 280(5367):1256-8.
Cibelli JB, Stice SL, Golueke PJ, Kane JJ, Jerry J, Blackwell C, Ponce de León FA, Robl JM.  1998.  Transgenic bovine chimeric offspring produced from somatic cell-derived stem-like cells.. Nat Biotechnol. 16(7):642-6.
Jerry DJ, Kuperwasser C, Downing SR, Pinkas J, He C, Dickinson E, Marconi S, Naber SP.  1998.  Delayed involution of the mammary epithelium in BALB/c-p53null mice.. Oncogene. 17(18):2305-12.
Jones FE, Jerry DJ, Guarino BC, Andrews GC, Stern DF.  1996.  Heregulin induces in vivo proliferation and differentiation of mammary epithelium into secretory lobuloalveoli.. Cell Growth Differ. 7(8):1031-8.
Jerry DJ, Medina D, Butel JS.  1994.  p53 mutations in COMMA-D cells.. In Vitro Cell Dev Biol Anim. 30A(2):87-9.
Jerry DJ, Butel JS, Donehower LA, Paulson EJ, Cochran C, Wiseman RW, Medina D.  1994.  Infrequent p53 mutations in 7,12-dimethylbenz[a]anthracene-induced mammary tumors in BALB/c and p53 hemizygous mice.. Mol Carcinog. 9(3):175-83.
Jerry DJ, Ozbun MA, Kittrell FS, Lane DP, Medina D, Butel JS.  1993.  Mutations in p53 are frequent in the preneoplastic stage of mouse mammary tumor development.. Cancer Res. 53(14):3374-81.
Jerry DJ, Griel LC, Kavanaugh JF, Kensinger RS.  1991.  Binding and bioactivity of ovine and porcine prolactins in porcine mammary tissue.. J Endocrinol. 130(1):43-51.
Birkenmeier EH, Gwynn B, Howard S, Jerry J, Gordon JI, Landschulz WH, McKnight SL.  1989.  Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein.. Genes Dev. 3(8):1146-56.
Jerry DJ, Stover RK, Kensinger RS.  1989.  Quantitation of prolactin-dependent responses in porcine mammary explants.. J Anim Sci. 67(4):1013-9.
Name Phone Office
Brown , Margarita ABBS Graduate Student 413-545-1129 465A
Roberts , Amy Lab Technician 413-545-1129 465A ISB
Former Lab Personnel