Barbara A. Osborne

Barbara A. Osborne

Professor

Director, MCB

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 697K - Advanced Immunology
ANIML SCI 794A - Immunology Journal Club

Induction of apoptosis in lymphocytes

The role of Notch signaling in T cell function

My laboratory studies two aspects of lymphocyte development and diversification. One area of active investigation in my laboratory is elucidation of the molecular events required for the induction of apoptosis in the mouse thymus. Negative selection (the removal of autoreactive T cells) occurs by an active cell death process known as apoptosis. To isolate genes that are required for this process, we constructed a cDNA library from dying thymocytes and isolated several genes that are induced or repressed during apoptosis. We have shown that several of these genes, such as p53 and Nur77, are required for cell death. Using techniques such as yeast two-hybrid analysis, we are now asking how these genes mediate cell death in T cells. Our two hybrid screen with Nur77 revealed that Notch-1 interacts with Nur77 and blocks Nur77 dependent apoptosis. Currently we are investigating the mechanism by which Notch-1 blocks Nur77 induced death.

Spinal cord sections from animals induced to develop EAE in the absence (A, B) oThe identification of Notch as an interaction partner of Nur77 lead us to further explore the role of Notch in T cell function. Recent data from the lab also has shown that signaling through the T cell receptor in peripheral T lymphocytes induces Notch-1 expression and this regulation of Notch expression in T cells plays an important and critical role in the function of various T cell subsets. We have found that Notch signaling is required for the development of Th1 cells. Th1 cells are known to play a role in several autoimmune diseases and in vivo blockade of Notch signaling blocks the induction of EAE, a murine disease with many of the characteristics of multiple sclerosis. Activation of Notch requires the enzyme g-secretase and current work is focused on the use of a g-secretase inhibitor to study how blockade of Notch signaling affects normal immune function.

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.
Osborne BA.  2011.  Notch, a T-ALL order.. Blood. 117(10):2749-50.
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.
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.
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.
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.
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.
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.
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, 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, 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.
Schwartz LM, Osborne BA.  1993.  Programmed cell death, apoptosis and killer genes.. Immunology today. 14(12):582-90.
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
Ayaz , Furkan MCB Graduate Student 413-545-1364 470 ISB
Lawlor , Rebecca Research Staff 413-545-1364 470 ISB
Mitra , Ankita Graduate Student 460 ISB
Munshi , Manit MCB Graduate Student 413-545-1364 470 ISB
Pierce , Carl Undergraduate Student 413-545-1364 470 ISB
Surampudi , Lalitha ABBS Graduate Student 413-545-1364 470 ISB
Former Lab Personnel