2006 Cell Signaling
Recent studies indicate that some people with lupus get better with a lowering of the number of B cells in their body. Normally, B cells produce antibodies designed to protect against foreign substances.
Working in mice, Dr. Garett-Sinha has found that a particular protein-Ets-1-limits the output of antibodies in B cells, including the kind of self-reactive antibodies that cause so much damage in lupus.
With LRI funding, she will further investigate this protein and hopefully generate findings that help in designing effective and less toxic therapies that control the B cell output of autoantibodies.
Ets-1 regulates plasma cell differentiation by interfering with the activity of the transcription factor Blimp-1. John, S.A., Clements, J.L., Russell, L.M. and Garrett-Sinha, L.A. 2008. J Biol Chem. 283:951-62.
IL-17 and the Th17 lineage in systemic lupus erythematosus. Garrett-Sinha, L.A., John, S.A. and Gaffen, S.L. 2008. Curr Opin Rheumatol. 20:519-25.
Blimp1: A conserved transcriptional repressor critical for differentiation of many tissues. John SA, Garrett-Sinha LA. Exp Cell Res. 2008 Dec 3.
2008 IP3 receptor-mediated Ca++ release in naive CD4 T cells dictates their cytokine program. Nagaleekar V, Diehl S, Juncadella I, Charland C, Garrett-Sinha, LA, Muthusamy N, Anguita J, Rincon M. J Immunol. 181:8315-22.
Dr. Garrett-Sinha is the subcontractor for an Alliance for Lupus Research award given to Dr. Sarah Gaffen at the University of Pittsburgh. As a subcontractor, Dr. Garrett-Sinha receives $6,600 to participate in the study aimed at defining signaling cascades downstream of the IL17R-C subunit, and to explore the possibility of interrupting IL-17 signaling as a therapeutic mechanism to treat lupus.