Therese Wiedmer, Ph.D.

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.