Barbara A. Osborne

Barbara A. Osborne

Professor

Director, MCB

Barbara A. Osborne, Ph.D.

Office phone: 413-545-4882

Lab phone: 413-545-1364

Fax: 413-545-1446

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

Office location: 427F ISB

Ph.D.: Stanford University, 1979
Postdoctoral Training: National Institutes of Health

ANIML SCI 572 - Infection and Immunity

ANIML SCI 697K - Advanced Immunology

ANIML SCI 794A - Immunology Journal Club

The Osborne laboratory focuses on the differentiation and function of mature CD4+ lymphocytes. In particular, we are interested in the role of Notch proteins in CD4+ maturation and function. Over the past several years, we have demonstrated that Notch plays a critical role in the differentiation of the T-helper 1 (Th1) and T-helper17 (Th17) subsets of T cells. Both Th1 and Th17 cells have been implicated in several diseases including experimental autoimmune encephalomyelitis (EAE), a mouse model of Multiple Sclerosis. Using gamma-secretase inhibitors (GSIs), compounds that block the activation of Notch, we have found that we can block the development of EAE in mice, suggesting that GSIs may be a possible therapeutic for the treatment of MS. Our current studies are focused on determining how Notch signaling influences the development of EAE as well as determining which Notch family member is important in the development of disease. In mammals, there are four Notch family members and it is unclear which Notch family member is most important in driving EAE.

Notch signaling is initiated by two enzymatic cleavages.  The first cleavage, driven by ADAM proteases, is required for the second cleavage, mediated by gamma-secretase, which results in the release of the intra-cellular domain of Notch and initiates the Notch signaling cascade.  Notch signaling can be blocked by gamma-secretase inhibitors and our lab, in collaboration with colleagues at UMass, UFlorida and LSU Medical School investigates how gamma secretase inhibition may be used to modulate immune responses.  We also are actively investigating whether Notch signaling in CD4+ T cells is mediated through canonical Notch signaling.  Our data suggest Notch signaling in T cells occurs through a non-canonical pathway and current research is focused on a clearer description of this non-canonical pathway.

Notch graphic

Our studies with gamma-secretase have led to a recognition that this enzyme may play a key role in regulating immune responses through its action on many immune receptors.  Gamma-secretase is a unique intramembranous enzyme that has the ability to cleave numerous Type I membrane proteins.  We are actively investigating the role of this enzyme in regulating the activity of a wide variety of immune receptors.

Additionally, in collaboration with our colleagues in the UMass IALS Center for Bioactive Delivery, we are actively engaged in developing tools that will allow us to selectively inhibit Notch signaling in potentially pathogenic T cells. In these studies, we are exploring how nanogels, carrying a variety of cargos, may be specifically targeted to selected T cell subsets.

Ran Y, Hossain F, Pannuti A, Lessard CB, Ladd GZ, Jung JI, Minter LM, Osborne BA, Miele L, Golde TE.  2017.  γ-Secretase inhibitors in cancer clinical trials are pharmacologically and functionally distinct.. {EMBO} Molecular Medicine. 9:950–966.
Sierra RA, Trillo-Tinoco J, Mohamed E, Yu L, Achyut BR, Arbab A, Bradford JW, Osborne BA, Miele L, Rodriguez PC.  2017.  Anti-Jagged Immunotherapy Inhibits MDSCs and Overcomes Tumor-Induced Tolerance. Cancer Research. 77:5628–5638.
Moyano D F, Liu Y, Ayaz F, Hou S, Puangploy P, Duncan B, Osborne B A, Rotello V M.  2016.  Immunomodulatory Effects of Coated Gold Nanoparticles in LPS-Stimulated In Vitro and In Vivo Murine Model Systems. Chem. 1:320–327.
Ozay EI, Gonzalez-Perez G, Torres JA, Vijayaraghavan J, Lawlor R, Sherman HL, Garrigan DT, Burnside AS, Osborne BA, Tew GN et al..  2016.  Intracellular Delivery of Anti-pPKC0 (Thr538) via Protein Transduction Domain Mimics for Immunomodulation. Molecular Therapy. 24:2118–2130.
Wang Y, Yu S, Huang D, Cui M, Hu H, Zhang L, Wang W, Parameswaran N, Jackson M, Osborne B et al..  2016.  Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1. The American Journal of Pathology. 186:2945–2956.
Gordon MR, Canakci M, Li L, Zhuang J, Osborne B, Thayumanavan S.  2015.  Field Guide to Challenges and Opportunities in Antibody–Drug Conjugates for Chemists. Bioconjugate Chemistry. 26:2198–2215.
Yun J, Espinoza I, Pannuti A, Romero D, Martinez L, Caskey M, Stanculescu A, Bocchetta M, Rizzo P, Band V et al..  2015.  p53 Modulates Notch Signaling in MCF-7 Breast Cancer Cells by Associating With the Notch Transcriptional Complex Via MAML1. Journal of Cellular Physiology. 230:3115–3127.
Prasad P, Molla MR, Cui W, Canakci M, Osborne B, Mager J, Thayumanavan S.  2015.  Polyamide Nanogels from Generally Recognized as Safe Components and Their Toxicity in Mouse Preimplantation Embryos.. Biomacromolecules. 16(11):3491-8.
Navasa N, Mart{\'ı}n I, Iglesias-Pedraz JM, Beraza N, Atondo E{\'ı}baliz, Izadi H, Ayaz F, Fernández-Álvarez S, Hatle K, Som A et al..  2014.  Regulation of Oxidative Stress by Methylation-Controlled J Protein Controls Macrophage Responses to Inflammatory Insults. Journal of Infectious Diseases. 211:135–145.
Ayaz F, Osborne BA.  2014.  Non-Canonical Notch Signaling in Cancer and Immunity. Frontiers in Oncology. 4
Dongre A, Surampudi L, Lawlor RG, Fauq AH, Miele L, Golde TE, Minter LM, Osborne BA.  2014.  Non-Canonical Notch Signaling Drives Activation and Differentiation of Peripheral CD4(+) T Cells.. Front Immunol. 5:54.
Sgolastra F, Minter LM, Osborne BA, Tew GN.  2014.  Importance of sequence specific hydrophobicity in synthetic protein transduction domain mimics.. Biomacromolecules. 15(3):812-20.
Shin HM, Tilahun ME, Cho OH, Chandiran K, Kuksin CA, Keerthivasan S, Fauq AH, Golde TE, Miele L, Thome M et al..  2014.  NOTCH1 Can Initiate NF-κB Activation via Cytosolic Interactions with Components of the T Cell Signalosome.. Front Immunol. 5:249.
Tezgel ÖA, Gonzalez-Perez G, Telfer JC, Osborne BA, Minter LM, Tew GN.  2013.  Novel protein transduction domain mimics as nonviral delivery vectors for siRNA targeting NOTCH1 in primary human T cells.. Mol Ther. 21(1):201-9.
Golde TE, Koo EH, Felsenstein KM, Osborne BA, Miele L.  2013.  γ (gamma)-Secretase inhibitors and modulators. Biochimica et Biophysica Acta ({BBA}) - Biomembranes. 1828:2898–2907.
Minter LM, Osborne BA.  2012.  Canonical and Non-Canonical Notch Signaling in CD4(+) T Cells.. Current topics in microbiology and immunology.
Minter LM, Osborne BA.  2012.  Notch and the survival of regulatory T cells: location is everything!. Science signaling. 5(234):pe31.
Das P, Verbeeck C, Minter L, Chakrabarty P, Felsenstein K, Kukar T, Maharvi G, Fauq A, Osborne BA, Golde TE.  2012.  Transient pharmacologic lowering of Aß production prior to deposition results in sustained reduction of amyloid plaque pathology.. Molecular neurodegeneration. 7(1):39.
Tilahun ME, Kwan A, Natarajan K, Quinn M, Tilahun AY, Xie C, Margulies DH, Osborne BA, Goldsby RA, Rajagopalan G.  2011.  Chimeric anti-staphylococcal enterotoxin B antibodies and lovastatin act synergistically to provide in vivo protection against lethal doses of SEB.. PloS one. 6(11):e27203.
Keerthivasan S, Suleiman R, Lawlor R, Roderick J, Bates T, Minter L, Anguita J, Juncadella I, Nickoloff BJ, Le Poole IC et al..  2011.  Notch signaling regulates mouse and human Th17 differentiation.. J Immunol. 187(2):692-701.
Osborne BA.  2011.  Notch, a T-ALL order.. Blood. 117(10):2749-50.
Juncadella IJ, Bates TC, Suleiman R, Monteagudo-Mera A, Olson CM, Navasa N, Olivera ER, Osborne BA, Anguita J.  2010.  The tick saliva immunosuppressor, Salp15, contributes to Th17-induced pathology during Experimental Autoimmune Encephalomyelitis.. Biochemical and biophysical research communications. 402(1):105-9.
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.
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.
Tilahun ME, Rajagopalan G, Shah-Mahoney N, Lawlor RG, Tilahun AY, Xie C, Natarajan K, Margulies DH, Ratner DI, Osborne BA et al..  2010.  Potent neutralization of staphylococcal enterotoxin B by synergistic action of chimeric antibodies.. Infection and immunity. 78(6):2801-11.
Wang A, Rud J, Olson CM, Anguita J, Osborne BA.  2009.  Phosphorylation of Nur77 by the MEK-ERK-RSK cascade induces mitochondrial translocation and apoptosis in T cells.. Journal of immunology (Baltimore, Md. : 1950). 183(5):3268-77.
Cho OH, Shin HM, Miele L, Golde TE, Fauq A, Minter LM, Osborne BA.  2009.  Notch regulates cytolytic effector function in CD8+ T cells.. Journal of immunology (Baltimore, Md. : 1950). 182(6):3380-9.
Joshi I, Minter LM, Telfer J, Demarest RM, Capobianco AJ, Aster JC, Sicinski P, Fauq A, Golde TE, Osborne BA.  2009.  Notch signaling mediates G1/S cell-cycle progression in T cells via cyclin D3 and its dependent kinases.. Blood. 113(8):1689-98.
Samon JB, Champhekar A, Minter LM, Telfer JC, Miele L, Fauq A, Das P, Golde TE, Osborne BA.  2008.  Notch1 and TGFbeta1 cooperatively regulate Foxp3 expression and the maintenance of peripheral regulatory T cells.. Blood. 112(5):1813-21.
Izadi H, Motameni AT, Bates TC, Olivera ER, Villar-Suarez V, Joshi I, Garg R, Osborne BA, Davis RJ, Rincón M et al..  2007.  c-Jun N-terminal kinase 1 is required for Toll-like receptor 1 gene expression in macrophages.. Infection and immunity. 75(10):5027-34.
Osborne BA, Minter LM.  2007.  Notch signalling during peripheral T-cell activation and differentiation.. Nature reviews. Immunology. 7(1):64-75.
Morgan GA, Guo Q, Chan SL, Gary DS, Osborne BA, Mattson MP.  2007.  Defects of immune regulation in the presenilin-1 mutant knockin mouse.. Neuromolecular medicine. 9(1):35-45.
Shin HM, Minter LM, Cho OH, Gottipati S, Fauq AH, Golde TE, Sonenshein GE, Osborne BA.  2006.  Notch1 augments NF-kappaB activity by facilitating its nuclear retention.. The EMBO journal. 25(1):129-38.
Osborne BA, Kee BL.  2005.  Lymphoid development: it's not 'all Greek to us' any more.. Nature immunology. 6(2):119-23.
Minter LM, Turley DM, Das P, Shin HM, Joshi I, Lawlor RG, Cho OH, Palaga T, Gottipati S, Telfer JC et al..  2005.  Inhibitors of gamma-secretase block in vivo and in vitro T helper type 1 polarization by preventing Notch upregulation of Tbx21.. Nature immunology. 6(7):680-8.
Laws AM, Osborne BA.  2004.  p53 regulates thymic Notch1 activation.. European journal of immunology. 34(3):726-34.
Tonomura N, McLaughlin K, Grimm L, Goldsby RA, Osborne BA.  2003.  Glucocorticoid-induced apoptosis of thymocytes: requirement of proteasome-dependent mitochondrial activity.. Journal of immunology (Baltimore, Md. : 1950). 170(5):2469-78.
Palaga T, Miele L, Golde TE, Osborne BA.  2003.  TCR-mediated Notch signaling regulates proliferation and IFN-gamma production in peripheral T cells.. Journal of immunology (Baltimore, Md. : 1950). 171(6):3019-24.
Minter LM, Osborne BA.  2003.  Cell death in the thymus--it' s all a matter of contacts.. Seminars in immunology. 15(3):135-44.
Ganguly BJ, Tonomura N, Benson RM, Osborne BA, Granowitz EV.  2002.  Hyperbaric oxygen enhances apoptosis in hematopoietic cells.. Apoptosis : an international journal on programmed cell death. 7(6):499-510.
Valavanis C, Hu Y, Yang Y, Osborne BA, Chouaib S, Greene L, Ashwell JD, Schwartz LM.  2001.  Model cell lines for the study of apoptosis in vitro.. Methods in cell biology. 66:417-36.
Jeong Y, Osborne BA, Goldsby RA.  2001.  Early Vlambda diversification in sheep.. Immunology. 103(1):26-34.
Osborne BA.  2000.  Transcriptional control of T cell development.. Current opinion in immunology. 12(3):301-6.
Grimm LM, Osborne BA.  1999.  Apoptosis and the proteasome.. Results and problems in cell differentiation. 23:209-28.
Morgan G, Smith S, Pak J, Marshak-Rothstein A, Fissore R, Osborne B.  1999.  Characterization of a mutant T-cell hybridoma line with defects in the TCR-mediated apoptotic pathway.. Cell death and differentiation. 6(1):36-47.
Jehn BM, Bielke W, Pear WS, Osborne BA.  1999.  Cutting edge: protective effects of notch-1 on TCR-induced apoptosis.. Journal of immunology (Baltimore, Md. : 1950). 162(2):635-8.
Lucier MR, Thompson RE, Waire J, Lin AW, Osborne BA, Goldsby RA.  1998.  Multiple sites of V lambda diversification in cattle.. Journal of immunology (Baltimore, Md. : 1950). 161(10):5438-44.
Meyer A, Parng CL, Hansal SA, Osborne BA, Goldsby RA.  1997.  Immunoglobulin gene diversification in cattle.. International reviews of immunology. 15(3-4):165-83.
Jehn BM, Osborne BA.  1997.  Gene regulation associated with apoptosis.. Critical reviews in eukaryotic gene expression. 7(1-2):179-93.
Grimm LM, Goldberg AL, Poirier GG, Schwartz LM, Osborne BA.  1996.  Proteasomes play an essential role in thymocyte apoptosis.. The EMBO journal. 15(15):3835-44.
Parng CL, Hansal S, Goldsby RA, Osborne BA.  1996.  Gene conversion contributes to Ig light chain diversity in cattle.. Journal of immunology (Baltimore, Md. : 1950). 157(12):5478-86.
Osborne BA, Smith SW, McLaughlin KA, Grimm L, Kallinch T, Liu Z, Schwartz LM.  1996.  Genes that regulate apoptosis in the mouse thymus.. Journal of cellular biochemistry. 60(1):18-22.
Osborne BA.  1996.  Cell death in vertebrates: lessons from the worm.. Trends in genetics : TIG. 12(12):489-91.
Osborne BA.  1996.  Apoptosis and the maintenance of homoeostasis in the immune system.. Current opinion in immunology. 8(2):245-54.
McLaughlin KA, Osborne BA, Goldsby RA.  1996.  The role of oxygen in thymocyte apoptosis.. European journal of immunology. 26(5):1170-4.
Osborne BA, Smith SW, McLaughlin KA, Grimm L, Morgan G, Goldsby RA.  1996.  Genetic regulation of apoptosis in the mouse thymus.. Advances in experimental medicine and biology. 406:199-207.
Osborne BA, Schwartz LM.  1995.  Cell death suffers a TKO.. BioEssays : news and reviews in molecular, cellular and developmental biology. 17(6):557-9.
Osborne BA, Smith SW, Liu ZG, McLaughlin KA, Schwartz LM.  1995.  Transient transfection assays to examine the requirement of putative cell death genes.. Methods in cell biology. 46:99-106.
Osborne BA.  1995.  Induction of genes during apoptosis: examples from the immune system.. Seminars in cancer biology. 6(1):27-33.
Smith SW, McLaughlin KA, Osborne BA.  1995.  Molecular events in thymocyte apoptosis.. Current topics in microbiology and immunology. 200:147-62.
Parng CL, Hansal S, Goldsby RA, Osborne BA.  1995.  Diversification of bovine lambda-light chain genes.. Annals of the New York Academy of Sciences. 764:155-7.
Osborne BA, Smith SW, Liu ZG, McLaughlin KA, Grimm L, Schwartz LM.  1994.  Identification of genes induced during apoptosis in T lymphocytes.. Immunological reviews. 142:301-20.
Schwartz LM, Osborne BA.  1994.  Ced-3/ICE: evolutionarily conserved regulation of cell death.. BioEssays : news and reviews in molecular, cellular and developmental biology. 16(6):387-9.
Osborne BA, Schwartz LM.  1994.  Essential genes that regulate apoptosis.. Trends in cell biology. 4(11):394-9.
Liu ZG, Smith SW, McLaughlin KA, Schwartz LM, Osborne BA.  1994.  Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77.. Nature. 367(6460):281-4.
Schwartz LM, Osborne BA.  1993.  Programmed cell death, apoptosis and killer genes.. Immunology today. 14(12):582-90.
Schwartz LM, Smith SW, Jones ME, Osborne BA.  1993.  Do all programmed cell deaths occur via apoptosis? Proceedings of the National Academy of Sciences of the United States of America. 90(3):980-4.
Ravichandran KS, Semproni AR, Goldsby RA, Osborne BA.  1992.  Immunoglobulin VH usage analysis by fluorescent in situ hybridization and flow cytometry.. Journal of immunological methods. 153(1-2):249-59.
Ferguson SE, Rudikoff S, Osborne BA.  1988.  Interaction and sequence diversity among T15 VH genes in CBA/J mice.. The Journal of experimental medicine. 168(4):1339-49.
Osborne BA, Golde TE, Schwartz RL, Rudikoff S.  1988.  Evolution of the IgA heavy chain gene in the genus Mus.. Genetics. 119(4):925-31.
Name Phone Office
Mitra , Ankita ABBS Graduate Student 413-545-1364 ISB 470
Robinson , Laura Administrative Assistant 413-545-5557 431A
Canakci , Mine OGraduate Student MCB 413-545-1364 ISB 470
Shanthalingam , Sudarvili Postdoctoral Research Associate 413-545-1364 ISB 470
Lawlor , Rebecca Research Staff 413-545-1364 ISB 470
Pierce , Carl Undergraduate Student 413-545-1364 ISB 470