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Sherry L. Spinelli, Ph.D.

Research Assistant Professor
of Pathology and Laboratory Medicine

Investigation of Platelets as Mediators of Inflammation

URMC Labs
601 Elmwood Ave., Rm 1-6429
Rochester, NY 14642-8608
Tel: (585) 273-3762
Fax: (585) 273-3637

Sherry_Spinelli@urmc.rochester.edu

Qualifications

Ph.D., University of Rochester 1999
Postdoctoral Fellow, Biochemistry/Biophysics, University of Rochester 1999-2000
Postdoctoral Fellow, Chemistry and Center for Human Genetics and Molecular Pediatrics, University of Rochester 2000-2003

Professional Activities

American Cancer Society Postdoctoral Fellowship 2001-2003

Research Overview

Platelets are enucleate cells released from megakaryocytes that circulate in the vascular system. Their importance and function in hemostasis is well known. Our (Drs. Neil Blumberg, Richard Phipps and myself) research interests lie in the emerging concept that platelets have a significant role in the mediation of inflammation and immunoregulation. Of particular interest is the nuclear hormone receptor, peroxisome proliferator-activated receptor gamma (PPARγ), part of a superfamily of ligand-activated receptors involved in transcriptional regulation of genes in energy metabolism and adipocyte differentiation. Several cell types including lymphocytes, fibroblasts, and endothelial cells express PPARγ. Interestingly, our laboratory has recently demonstrated that human platelets also express PPARγ and receptor binding of PPARγ by PPARγ agonists reduces platelet release of proinflammatory mediators. This is of major significance as platelet activation is linked to several diseases including atherosclerosis, insulin resistance in type II diabetes, and cancer. My goal is to understand the role of platelet PPARγ in inflammation. This research is conducted in collaboration with the laboratory of Dr. Richard Phipps.

Platelet transfusion can cause a life-threatening inflammatory response. Upon activation, platelets undergo rapid morphological changes, and release bioactive mediators including chemokines, prostaglandins and growth factors that elicit a variety of responses. We will investigate the role of platelet-released proinflammatory mediators in transfusion-associated inflammation and multi-organ failure. Our goal is to develop a therapeutic strategy to reduce the risk of inflammatory responses in patients transfused with platelets.

Publications

Ray DM, Spinelli SL, Pollock SJ, Murant TI, O'Brien JJ, Blumberg N, Francis CW, Taubman MB, Phipps RP. Peroxisome proliferator-activated receptor gamma and retinoid X receptor transcription factors are released from activated human platelets and shed in microparticles. Thromb Haemost. 2008 Jan;99(1):86-95.

Spinelli SL, O'Brien JJ, Bancos S, Lehmann GM, Springer D, Blumberg N, Francis CW, Taubman MB, Phipps RP. The PPAR-platelet connection: modulators of inflammation and potential cardiovascular effects. PPAR Research 2008, Article ID 328172, 16 pages.

Kaufman J, Spinelli SL, Schultz E, Blumberg N, Phipps RP. Release of biologically active CD154 during collection and storage of platelet concentrates prepared for transfusion. J Thromb Haemost. 2007 Apr;5(4):788-96.

O'Brien JJ, Ray DM, Spinelli SL, Blumberg N, Taubman MB, Francis CW, Wittlin SD, Phipps RP. The platelet as a therapeutic target for treating vascular diseases and the role of eicosanoid and synthetic PPARgamma ligands. Prostaglandins Other Lipid Mediat. 2007 Jan;82(1-4):68-76.

Ray DM, Spinelli SL, O'Brien JJ, Blumberg N, Phipps RP. Platelets as a novel target for PPARgamma ligands : implications for inflammation, diabetes, and cardiovascular disease. BioDrugs. 2006;20(4):231-41.

Shull NP, Spinelli SL, Phizicky EM. A highly specific phosphatase that acts on ADP-ribose 1''-phosphate, a metabolite of tRNA splicing in Saccharomyces cerevisiae. Nucleic Acids Res. 2005 Jan 31;33(2):650-60. Print 2005.

Ruschak AM, Mathews DH, Bibillo A, Spinelli SL, Childs JL, Eickbush TH, Turner DH. Secondary structure models of the 3' untranslated regions of diverse R2 RNAs. RNA. 2004 Jun;10(6):978-87.

Phizicky EM, Martzen MR, McCraith SM, Spinelli SL, Xing F, Shull NP, Van Slyke C, Montagne RK, Torres FM, Fields S, Grayhack EJ. Biochemical genomics approach to map activities to genes. Methods Enzymol. 2002;350:546-59.

Kierzek R, Steiger MA, Spinelli SL, Turner DH, Phizicky EM. The chemical synthesis of oligoribonucleotides with selectively placed 2'-O-phosphates. Nucleosides Nucleotides Nucleic Acids. 2000 May-Jun;19(5-6):917-33.

Martzen MR, McCraith SM, Spinelli SL, Torres FM, Fields S, Grayhack EJ, Phizicky EM. A biochemical genomics approach for identifying genes by the activity of their products. Science. 1999 Nov 5;286(5442):1153-5.

Spinelli SL, Kierzek R, Turner DH, Phizicky EM. Transient ADP-ribosylation of a 2'-phosphate implicated in its removal from ligated tRNA during splicing in yeast. J Biol Chem. 1999 Jan 29;274(5):2637-44.

Spinelli SL, Malik HS, Consaul SA, Phizicky EM. A functional homolog of a yeast tRNA splicing enzyme is conserved in higher eukaryotes and in Escherichia coli. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14136-41.

Spinelli SL, Consaul SA, Phizicky EM. A conditional lethal yeast phosphotransferase (tpt1) mutant accumulates tRNAs with a 2'-phosphate and an undermodified base at the splice junction. RNA. 1997 Dec;3(12):1388-400.

Sowden M, Hamm JK, Spinelli S, Smith HC. Determinants involved in regulating the proportion of edited apolipoprotein B RNAs. RNA. 1996 Mar;2(3):274-88.