Sharon Nahill
Genzyme
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Publication
Featured researches published by Sharon Nahill.
Transplantation | 2009
Gina Lacorcia; Mark Swistak; Carla Lawendowski; Su Duan; Tim Weeden; Sharon Nahill; John M. Williams; John Lyle Dzuris
Background. Polyclonal antithymocyte globulins (ATGs) are used clinically to prevent and treat acute allograft rejection and are believed to modulate the immune response primarily by depleting T cells. However, nondepleting mechanisms may also be important mediators of graft survival. In the present study, 14 lots of thymoglobulin (rabbit ATG) were analyzed and compared for nondepletive immunomodulatory activities in vitro. Methods. Coincubation of human peripheral blood mononuclear cells with thymoglobulin induces CD4+CD25highFoxp3+ regulatory T cells, which were evaluated for consistent ability to suppress T-cell activation in mixed lymphocyte reactions. The consistency of CD2, CD3, CD11a, and CD45 antigen specificities in thymoglobulin was determined using flow cytometry to measure inhibition of fluorescent monoclonal antibody binding to Jurkat T cells. A transwell chemotaxis assay was established and used to evaluate ATG-mediated inhibition of stromal cell-derived factor (SDF)-1α-driven Jurkat T-cell migration. Results. Physiologic levels of thymoglobulin produced nondepletive immunomodulatory activities, which were consistent from batch to batch. All lots of thymoglobulin induced functionally immunosuppressive regulatory T cells and inhibited monoclonal antibody binding to key T-cell surface antigens. In addition, these studies provide the first demonstration that thymoglobulin effectively inhibits CXCR4/SDF-1α-driven T-cell chemotaxis. Conclusions. This novel, systematic in vitro analysis of 14 different manufactured lots of thymoglobulin demonstrates the overall consistency of this product and provides further insights into nondepletive mechanisms by which thymoglobulin may generate durable immunoregulation and allograft survival.
Transplantation | 2007
Melanie Ruzek; John Lyle Dzuris; Lan Gao; Russell Bigelow; James Waire; Abraham Scaria; Sharon Nahill; John M. Williams
A murine anti-thymocyte globulin, which was made in rabbits using the same manufacturing protocol used in production of Thymoglobulin (Genzyme Transplant, Cambridge, MA), was used to explore the biology and mechanism of action of Thymoglobulin. These preclinical studies suggest that determining optimal dosing and timing of Thymoglobulin can contribute to maximizing protection against allograft rejection. The murine anti-thymocyte globulin has a demonstrated ability to induce cells in vitro with a T-regulatory phenotype and was also shown to be effective in vivo in protecting mice against acute GVHD and in reversing overt diabetes in nonobese diabetic mice. The mechanistic rationale for Thymoglobulin as a therapeutic agent for the treatment of systemic lupus erythematosus, multiple myeloma, and myelodysplastic syndrome was also explored.
Bioorganic & Medicinal Chemistry Letters | 2003
John L. Kane; Bradford Hirth; Beirong Liang; Brian B. Gourlie; Sharon Nahill; Gary Barsomian
Blood | 2007
Melanie Ruzek; James Waire; Deborah A. Hopkins; Gina Lacorcia; Jennifer Sullivan; Bruce L. Roberts; Susan M. Richards; Sharon Nahill; John M. Williams; Abraham Scaria; John Lyle Dzuris; Srinivas Shankara; Richard D. Garman
International Immunology | 2007
Denise T. Chung; Thomas Korn; Julie Richard; Melanie Ruzek; Adam P. Kohm; Stephen D. Miller; Sharon Nahill; Mohamed Oukka
Archive | 2001
Scott F. Sneddon; John L. Kane; Bradford Hirth; Frederic Vinick; Shuang Qiao; Sharon Nahill; John M. Williams; Hans-Peter Biemann
Clinical Immunology | 2007
Denise Chung; Thomas Korn; Julie Richard; Adam P. Kohm; Melanie Ruzek; Mohamed Oukka; Stephen D. Miller; Sharon Nahill; Vijay K. Kuchroo
Archive | 2010
Srinivas Shankara; Richard D. Garman; Susan Richards; Sharon Nahill; John M. Williams; Abraham Scaria; John Lyle Dzuris; Melanie Ruzek; James Waire; Deborah A. Hopkins; Jennifer Sullivan; Laura L. Bruce
Archive | 2001
Scott F. Sneddon; John L. Kane; Bradford Hirth; Fred Vinick; Shuang Qiao; Sharon Nahill; M Williams John; Biemann Hans-Peter
Archive | 2001
John M. Williams; Hans-Peter Biemann; Andrew Janjigian; Scott F. Sneddon; John L. Kane; Bradford Hirth; Fred Vinick; Shuang Qiao; Sharon Nahill