Platelets are anucleate 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 (PPARgamma), 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 PPARgamma. Interestingly, our laboratory has recently demonstrated that human platelets also express PPARgamma and receptor binding of PPARgamma by PPARgamma 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 PPARgamma 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.

• Sahler J, Woeller C, Spinelli S, Blumberg N, Phipps R. A novel method for overexpression of peroxisome proliferator-activated receptor-? in megakaryocyte and platelet microparticles achieves transcellular signaling. J Thromb Haemost. 2012 Dec; 10(12):2563-72.
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• Lannan KL, Sahler J, Spinelli SL, Phipps RP, Blumberg N. Transfusion immunomodulation - the case for leukoreduced and (perhaps) washed transfusions. Blood Cells Mol Dis. 2013 Jan; 50(1):61-8.
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• Sahler J, Spinelli S, Phipps R, Blumberg N. CD40 ligand (CD154) involvement in platelet transfusion reactions. Transfus Clin Biol. 2012 Jun; 19(3):98-103.
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• Refaai MA, Carter J, Henrichs KF, Davidson DC, Pollock SJ, Casey AE, Spinelli SL, Phipps RP, Francis CW, Blumberg N. Alterations of platelet function and clot formation kinetics after in vitro exposure to anti-A and -B. Transfusion. 2013 Feb; 53(2):382-93.
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• Cholette JM, Henrichs KF, Alfieris GM, Powers KS, Phipps R, Spinelli SL, Swartz M, Gensini F, Daugherty LE, Nazarian E, Rubenstein JS, Sweeney D, Eaton M, Lerner NB, Blumberg N. Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: Results of a prospective, randomized, controlled clinical trial*. Pediatr Crit Care Med. 2012 May; 13(3):290-9.
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• Grimshaw K, Sahler J, Spinelli SL, Phipps RP, Blumberg N. New frontiers in transfusion biology: identification and significance of mediators of morbidity and mortality in stored red blood cells. Transfusion. 2011 Apr; 51(4):874-80.
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• Refaai MA, Fialkow LB, Heal JM, Henrichs KF, Spinelli SL, Phipps RP, Masel E, Smith BH, Corsetti JP, Francis CW, Bankey PE, Blumberg N. An association of ABO non-identical platelet and cryoprecipitate transfusions with altered red cell transfusion needs in surgical patients. Vox Sang. 2011 Jul; 101(1):55-60.
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• Sahler J, Bernard JJ, Spinelli SL, Blumberg N, Phipps RP. The Feverfew plant-derived compound, parthenolide enhances platelet production and attenuates platelet activation through NF-?B inhibition. Thromb Res. 2011 May; 127(5):426-34.
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• Davidson DC, Hirschman MP, Spinelli SL, Morrell CN, Schifitto G, Phipps RP, Maggirwar SB. Antiplatelet activity of valproic acid contributes to decreased soluble CD40 ligand production in HIV type 1-infected individuals. J Immunol. 2011 Jan 1; 186(1):584-91.
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• Refaai MA, Phipps RP, Spinelli SL, Blumberg N. Platelet transfusions: impact on hemostasis, thrombosis, inflammation and clinical outcomes. Thromb Res. 2011 Apr; 127(4):287-91.
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• Spinelli SL, Maggirwar SB, Blumberg N, Phipps RP. Nuclear emancipation: a platelet tour de force. Sci Signal. 2010; 3(144):pe37.
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• Simpson-Haidaris PJ, Seweryniak KE, Spinelli SL, Garcia-Bates TM, Murant TI, Pollock SJ, Sime PJ, Phipps RP. A putative role for platelet-derived PPAR? in vascular homeostasis demonstrated by anti-PPAR? induction of bleeding, thrombocytopenia and compensatory megakaryocytopoiesis. J Biotechnol. 2010 Nov; 150(3):417-27.
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• Spinelli SL, Casey AE, Pollock SJ, Gertz JM, McMillan DH, Narasipura SD, Mody NA, King MR, Maggirwar SB, Francis CW, Taubman MB, Blumberg N, Phipps RP. Platelets and megakaryocytes contain functional nuclear factor-kappaB. Arterioscler Thromb Vasc Biol. 2010 Mar; 30(3):591-8.
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• Bernard JJ, Seweryniak KE, Koniski AD, Spinelli SL, Blumberg N, Francis CW, Taubman MB, Palis J, Phipps RP. Foxp3 regulates megakaryopoiesis and platelet function. Arterioscler Thromb Vasc Biol. 2009 Nov; 29(11):1874-82.
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• Springer DL, Miller JH, Spinelli SL, Pasa-Tolic L, Purvine SO, Daly DS, Zangar RC, Jin S, Blumberg N, Francis CW, Taubman MB, Casey AE, Wittlin SD, Phipps RP. Platelet proteome changes associated with diabetes and during platelet storage for transfusion. J Proteome Res. 2009 May; 8(5):2261-72.
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• Blumberg N, Spinelli SL, Francis CW, Taubman MB, Phipps RP. The platelet as an immune cell-CD40 ligand and transfusion immunomodulation. Immunol Res. 2009; 45(2-3):251-60.
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• O'Brien JJ, Spinelli SL, Tober J, Blumberg N, Francis CW, Taubman MB, Palis J, Seweryniak KE, Gertz JM, Phipps RP. 15-deoxy-delta12,14-PGJ2 enhances platelet production from megakaryocytes. Blood. 2008 Nov 15; 112(10):4051-60.
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• Spinelli SL, O'Brien JJ, Bancos S, Lehmann GM, Springer DL, Blumberg N, Francis CW, Taubman MB, Phipps RP. The PPAR-Platelet Connection: Modulators of Inflammation and Potential Cardiovascular Effects. PPAR Res. 2008; 2008:328172.
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• 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.
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• 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.
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• 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.
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• 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.
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• Shull NP, Spinelli SL, Phizicky EM. We are writing to express our concerns regarding the recently published article by Kumaran et al. Protein Sci. 2005 Dec; 14(12):3145; author reply 3145.
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• 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; 33(2):650-60.
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• 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.
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• 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.
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• 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.
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• 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.
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• 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.
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• 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.
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• 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.
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• Qian M, Spinelli S, Driguez H, Payan F. Structure of a pancreatic alpha-amylase bound to a substrate analogue at 2.03 A resolution. Protein Sci. 1997 Nov; 6(11):2285-96.
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• 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.
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• Dominguez R, Souchon H, Spinelli S, Dauter Z, Wilson KS, Chauvaux S, Béguin P, Alzari PM. A common protein fold and similar active site in two distinct families of beta-glycanases. Nat Struct Biol. 1995 Jul; 2(7):569-76.
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