Our laboratory is focusing on a family of proteins called phospholipid scramblases. We originally cloned phospholipid scramblase 1 (PLSCR1), a Ca2+-binding, endofacial plasma membrane protein, based on its capacity to promote rapid transbilayer movement of phospholipids in response to elevated Ca2+. Such redistribution of phospholipids is normally observed upon platelet activation, and in injured or apoptotic cells. We subsequently identified three additional members of this gene family. Recent data from our laboratory suggest a considerably more complex biology for these proteins than their putative role in mediating transbilayer lipid movement. PLSCR1 -- and possibly other members of the PLSCR gene family -- plays a role in modulating the signal transduction through multiple growth factor receptors, and is itself transcriptionally upregulated through these same growth factor receptor pathways. We also discovered that when transcriptionally induced, a portion of the newly synthesized PLSCR1 translocates to the nucleus, in addition to its usual location at the plasma membrane, where it can increase gene transcription. One such gene identified to be upregulated in presence of PLSCR1 is the IP3-receptor type 1. Our current efforts are aimed at elucidating the role of PLSCRs in diverse signaling pathways underlying proliferation, differentiation, and apoptosis.
BS | Switzerland-Univ of Bern
PhD | Switzerland-Univ of Bern
Merrick Award for scientific Research
Oklahoma Medical Research Foundation
Fellow, American Heart Association
Kassas A, Moura IC, Yamashita Y, Scheffel J, Guérin-Marchand C, Blank U, Sims PJ, Wiedmer T, Monteiro RC, Rivera J, Charles N, Benhamou M. "Regulation of the tyrosine phosphorylation of Phospholipid Scramblase 1 in mast cells that are stimulated through the high-affinity IgE receptor." PloS one.. 2014 9(10):e109800. Epub 2014 Oct 07.
Li D, Yang H, Nan H, Liu P, Pang S, Zhao Q, Karni R, Kamps MP, Xu Y, Zhou J, Wiedmer T, Sims PJ, Wang F. "Identification of key regulatory pathways of myeloid differentiation using an mESC-based karyotypically normal cell model." Blood.. 2012 Dec 6; 120(24):4712-9. Epub 2012 Oct 18.
Chen CW, Sowden M, Zhao Q, Wiedmer T, Sims PJ. "Nuclear phospholipid scramblase 1 prolongs the mitotic expansion of granulocyte precursors during G-CSF-induced granulopoiesis." Journal of leukocyte biology.. 2011 Aug; 90(2):221-33. Epub 2011 Mar 29.
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