The University of Massachusetts Amherst

Barbara A. Osborne

Professor

My 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.

Current Research
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. Additionally, in collaboration with our colleagues in the 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.

Learn more at www.vasci.umass.edu/research-faculty/barbara-a-osborne

Academic Background

  • BA, English, Moravian College, 1970
  • PhD, Genetic & Immunology, Stanford University Medical School, 1979
  • Damon Runyon Postdoctoral fellow, National Institutes of Health, 1979-83
Sierra RA, Trillo-Tinoco J, Mohamed E, Yu L, Achyut BR, Arbab A, Bradford JW, Osborne BA, Miele L, Rodriguez PC. Anti-Jagged Immunotherapy Inhibits MDSCs and Overcomes Tumor-Induced Tolerance. Cancer Res. 2017 Oct 15;77(20):5628-5638. doi: 10.1158/0008-5472.CAN-17-0357. Epub 2017 Sep 13. PubMed PMID: 28904063; PubMed Central PMCID: PMC5679354.
Ran Y, Hossain F, Pannuti A, Lessard CB, Ladd GZ, Jung JI, Minter LM, Osborne BA, Miele L, Golde TE. γ-Secretase inhibitors in cancer clinical trials are pharmacologically and functionally distinct. EMBO Mol Med. 2017 Jul;9(7):950-966. doi: 10.15252/emmm.201607265. PubMed PMID: 28539479; PubMed Central PMCID: PMC5494507.
Ozay EI, Gonzalez-Perez G, Torres JA, Vijayaraghavan J, Lawlor R, Sherman HL, Garrigan DT Jr, Burnside AS, Osborne BA, Tew GN, Minter LM. Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation. Mol Ther. 2016 Dec;24(12):2118-2130. doi: 10.1038/mt.2016.177. Epub 2016 Sep 16. PubMed PMID: 27633441; PubMed Central PMCID: PMC5167783.
Wang Y, Yu S, Huang D, Cui M, Hu H, Zhang L, Wang W, Parameswaran N, Jackson M, Osborne B, Bedogni B, Li C, Sy MS, Xin W, Zhou L. Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1. Am J Pathol. 2016 Nov;186(11):2945-2956. doi: 10.1016/j.ajpath.2016.07.010. Epub 2016 Sep 14. PubMed PMID: 27639164.
Moyano DF, Liu Y, Ayaz F, Hou S, Puangploy P, Duncan B, Osborne BA, Rotello VM. Immunomodulatory effects of coated gold nanoparticles in LPS-stimulated in vitro and in vivo murine model systems. Chem. 2016;1(2):320-327. doi:10.1016/j.chempr.2016.07.007. Epub 2016 Aug 11. PubMed PMID: 28255579; PubMed Central PMCID: PMC5328597.
Wongchana W, Lawlor RG, Osborne BA, Palaga T. Impact of Notch1 Deletion in Macrophages on Proinflammatory Cytokine Production and the Outcome of Experimental Autoimmune Encephalomyelitis. J Immunol. 2015 Dec 1;195(11):5337-46 doi: 10.4049/jimmunol.1401770. Epub 2015 Oct 26. PubMed PMID: 26503951; PubMed Central PMCID: PMC4691704.
Prasad P, Molla MR, Cui W, Canakci M, Osborne B, Mager J, Thayumanavan S. Polyamide Nanogels from Generally Recognized as Safe Components and Their Toxicity in Mouse Preimplantation Embryos. Biomacromolecules. 2015 Nov 9;16(11):3491-8. doi: 10.1021/acs.biomac.5b00900. Epub 2015 Oct 6. PubMed PMID: 26367020; PubMed Central PMCID: PMC4970214.
Gordon MR, Canakci M, Li L, Zhuang J, Osborne B, Thayumanavan S. Field Guide to Challenges and Opportunities in Antibody-Drug Conjugates for Chemists. Bioconjug Chem. 2015 Nov 18;26(11):2198-215. doi: 10.1021/acs.bioconjchem.5b00399. Epub 2015 Sep 10. Review. PubMed PMID: 26308881; PubMed Central PMCID: PMC4933296.
Yun J, Espinoza I, Pannuti A, Romero D, Martinez L, Caskey M, Stanculescu A, Bocchetta M, Rizzo P, Band V, Band H, Kim HM, Park SK, Kang KW, Avantaggiati ML, Gomez CR, Golde T, Osborne B, Miele L. p53 Modulates Notch Signaling in MCF-7 Breast Cancer Cells by Associating With the Notch Transcriptional Complex Via MAML1. J Cell Physiol. 2015 Dec;230(12):3115-27. doi: 10.1002/jcp.25052. PubMed PMID: 26033683; PubMed Central PMCID: PMC4549197.
Ayaz F, Osborne BA. Non-canonical notch signaling in cancer and immunity. Front Oncol. 2014 Dec 4;4:345. doi: 10.3389/fonc.2014.00345. eCollection 2014. Review. PubMed PMID: 25538890; PubMed Central PMCID: PMC4255497.
Shin HM, Tilahun ME, Cho OH, Chandiran K, Kuksin CA, Keerthivasan S, Fauq AH, Golde TE, Miele L, Thome M, Osborne BA, Minter LM. NOTCH1 Can Initiate NF-κB Activation via Cytosolic Interactions with Components of the T Cell Signalosome. Front Immunol. 2014 May 26;5:249. doi: 10.3389/fimmu.2014.00249. eCollection 2014. PubMed PMID: 24904593; PubMed Central PMCID: PMC4033603.
Dongre A, Surampudi L, Lawlor RG, Fauq AH, Miele L, Golde TE, Minter LM, Osborne BA. Non-Canonical Notch Signaling Drives Activation and Differentiation of Peripheral CD4(+) T Cells. Front Immunol. 2014 Feb 12;5:54. doi: 10.3389/fimmu.2014.00054. eCollection 2014. PubMed PMID: 24611064; PubMed Central PMCID: PMC3921607.
Sgolastra F, Minter LM, Osborne BA, Tew GN. Importance of sequence specific hydrophobicity in synthetic protein transduction domain mimics. Biomacromolecules. 2014 Mar 10;15(3):812-20. doi: 10.1021/bm401634r. Epub 2014 Feb 26. PubMed PMID: 24506414.
Golde TE, Koo EH, Felsenstein KM, Osborne BA, Miele L. γ-Secretase inhibitors and modulators. Biochim Biophys Acta. 2013 Dec;1828(12):2898-907. doi: 10.1016/j.bbamem.2013.06.005. Epub 2013 Jun 17. Review. PubMed PMID: 23791707; PubMed Central PMCID: PMC3857966.
Tezgel AÖ, Gonzalez-Perez G, Telfer JC, Osborne BA, Minter LM, Tew GN. Novel protein transduction domain mimics as nonviral delivery vectors for siRNA targeting NOTCH1 in primary human T cells. Mol Ther. 2013 Jan;21(1):201-9. doi: 10.1038/mt.2012.209. Epub 2012 Oct 16. PubMed PMID: 23070119; PubMed Central PMCID: PMC3538314.
 
Contact Info

Department of Veterinary & Animal Sciences
427F Integrated Sciences Building
660 North Pleasant Street
Amherst, MA 01003

(413) 545-4882
osborne@vasci.umass.edu

www.vasci.umass.edu/research-faculty/barbara-a-osborne