Barbara A. Osborne

Barbara A. Osborne

Professor

Office: 

427F ISB

Office phone: 

413-545-4882

Lab phone: 

413-545-1364

Fax: 

413-545-1446

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

Classes: 

ANIMLSCI 697K - Advanced Immunology

ANIMLSCI 794A - Immunology Journal Club

Research Interests

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.

Lab Personnel

Name Email Phone Office
Lawlor, Rebecca
Research Staff
blawlor [at] vasci.umass.edu 413-545-1364 ISB 470
Pierce, Carl
Undergraduate Student
capierce [at] umass.edu 413-545-1364 ISB 470

Publications

Majumder, S., Crabtree, J. S., Golde, T. E., Minter, L. M., Osborne, B. A., & Miele, L.. (2021). Targeting Notch in oncology: the path forward. Nat Rev Drug Discov, 20(2), 125-144. presented at the 2021 02. doi:10.1038/s41573-020-00091-3
Majumder, S., Crabtree, J. S., Golde, T. E., Minter, L. M., Osborne, B. A., & Miele, L.. (2021). Targeting Notch in oncology: the path forward. Nat Rev Drug Discov, 20(2), 125-144. presented at the 2021 02. doi:10.1038/s41573-020-00091-3
Moyano, D. F., Liu, Y., Ayaz, F., Hou, S., Puangploy, P., Duncan, B., et al.. (2016). Immunomodulatory effects of coated gold nanoparticles in LPS-stimulated and murine model systems. Chem, 1(2), 320-327. presented at the 2016. doi:10.1016/j.chempr.2016.07.007
Ganguly, B. J., Tonomura, N., Benson, R. M., Osborne, B. A., & Granowitz, E. V.. (2002). Hyperbaric oxygen enhances apoptosis in hematopoietic cells. Apoptosis : an international journal on programmed cell death, 7(6), 499-510. presented at the 2002 Dec.
Valavanis, C., Hu, Y., Yang, Y., Osborne, B. A., Chouaib, S., Greene, L., et al.. (2001). Model cell lines for the study of apoptosis in vitro. Methods in cell biology, 66, 417-36. presented at the 2001.
Jeong, Y., Osborne, B. A., & Goldsby, R. A.. (2001). Early Vlambda diversification in sheep. Immunology, 103(1), 26-34. presented at the 2001 May.
Osborne, B. A. (2000). Transcriptional control of T cell development. Current opinion in immunology, 12(3), 301-6. presented at the 2000 Jun.
Jehn, B. M., Bielke, W., Pear, W. S., & Osborne, B. A.. (1999). Cutting edge: protective effects of notch-1 on TCR-induced apoptosis. Journal of immunology (Baltimore, Md. : 1950), 162(2), 635-8. presented at the 1999 Jan 15.
Grimm, L. M., & Osborne, B. A.. (1999). Apoptosis and the proteasome. Results and problems in cell differentiation, 23, 209-28. presented at the 1999.
Lucier, M. R., Thompson, R. E., Waire, J., Lin, A. W., Osborne, B. A., & Goldsby, R. A.. (1998). Multiple sites of V lambda diversification in cattle. Journal of immunology (Baltimore, Md. : 1950), 161(10), 5438-44. presented at the 1998 Nov 15.
Meyer, A., Parng, C. L., Hansal, S. A., Osborne, B. A., & Goldsby, R. A.. (1997). Immunoglobulin gene diversification in cattle. International reviews of immunology, 15(3-4), 165-83. presented at the 1997.
Jehn, B. M., & Osborne, B. A.. (1997). Gene regulation associated with apoptosis. Critical reviews in eukaryotic gene expression, 7(1-2), 179-93. presented at the 1997.
Osborne, B. A. (1996). Apoptosis and the maintenance of homoeostasis in the immune system. Current opinion in immunology, 8(2), 245-54. presented at the 1996 Apr.
McLaughlin, K. A., Osborne, B. A., & Goldsby, R. A.. (1996). The role of oxygen in thymocyte apoptosis. European journal of immunology, 26(5), 1170-4. presented at the 1996 May.
Parng, C. L., Hansal, S., Goldsby, R. A., & Osborne, B. A.. (1996). Gene conversion contributes to Ig light chain diversity in cattle. Journal of immunology (Baltimore, Md. : 1950), 157(12), 5478-86. presented at the 1996 Dec 15.
Osborne, B. A., Smith, S. W., McLaughlin, K. A., Grimm, L., Morgan, G., & Goldsby, R. A.. (1996). Genetic regulation of apoptosis in the mouse thymus. Advances in experimental medicine and biology, 406, 199-207. presented at the 1996.
Osborne, B. A., Smith, S. W., McLaughlin, K. A., Grimm, L., Kallinch, T., Liu, Z., & Schwartz, L. M.. (1996). Genes that regulate apoptosis in the mouse thymus. Journal of cellular biochemistry, 60(1), 18-22. presented at the 1996 Jan.
Osborne, B. A. (1996). Cell death in vertebrates: lessons from the worm. Trends in genetics : TIG, 12(12), 489-91. presented at the 1996 Dec.
Grimm, L. M., Goldberg, A. L., Poirier, G. G., Schwartz, L. M., & Osborne, B. A.. (1996). Proteasomes play an essential role in thymocyte apoptosis. The EMBO journal, 15(15), 3835-44. presented at the 1996 Aug 1.
Osborne, B. A., & Schwartz, L. M.. (1995). Cell death suffers a TKO. BioEssays : news and reviews in molecular, cellular and developmental biology, 17(6), 557-9. presented at the 1995 Jun.
Parng, C. L., Hansal, S., Goldsby, R. A., & Osborne, B. A.. (1995). Diversification of bovine lambda-light chain genes. Annals of the New York Academy of Sciences, 764, 155-7. presented at the 1995 Sep 29.
Osborne, B. A. (1995). Induction of genes during apoptosis: examples from the immune system. Seminars in cancer biology, 6(1), 27-33. presented at the 1995 Feb.
Smith, S. W., McLaughlin, K. A., & Osborne, B. A.. (1995). Molecular events in thymocyte apoptosis. Current topics in microbiology and immunology, 200, 147-62. presented at the 1995.
Osborne, B. A., & Schwartz, L. M.. (1994). Essential genes that regulate apoptosis. Trends in cell biology, 4(11), 394-9. presented at the 1994 Nov.
Schwartz, L. M., & Osborne, B. A.. (1994). Ced-3/ICE: evolutionarily conserved regulation of cell death. BioEssays : news and reviews in molecular, cellular and developmental biology, 16(6), 387-9. presented at the 1994 Jun.
Schwartz, L. M., Smith, S. W., Jones, M. E., & Osborne, B. A.. (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. presented at the 1993 Feb 1.
Schwartz, L. M., & Osborne, B. A.. (1993). Programmed cell death, apoptosis and killer genes. Immunology today, 14(12), 582-90. presented at the 1993 Dec.
Ravichandran, K. S., Semproni, A. R., Goldsby, R. A., & Osborne, B. A.. (1992). Immunoglobulin VH usage analysis by fluorescent in situ hybridization and flow cytometry. Journal of immunological methods, 153(1-2), 249-59. presented at the 1992 Aug 30.
Ferguson, S. E., Rudikoff, S., & Osborne, B. A.. (1988). Interaction and sequence diversity among T15 VH genes in CBA/J mice. The Journal of experimental medicine, 168(4), 1339-49. presented at the 1988 Oct 1.
Osborne, B. A., Golde, T. E., Schwartz, R. L., & Rudikoff, S.. (1988). Evolution of the IgA heavy chain gene in the genus Mus. Genetics, 119(4), 925-31. presented at the 1988 Aug.