To investigate and measure the functional significance of altered P2Y12 expression in the context of human microglia activation.
We performed in vitro and in situ experiments to measure how P2Y12 expression can influence disease-relevant functional properties of classically activated (M1) and alternatively activated (M2) human microglia in the inflamed brain.
We demonstrated that compared to resting and classically activated (M1) human microglia, P2Y12 expression is increased under alternatively activated (M2) conditions. In response to ADP, the endogenous ligand of P2Y12, M2 microglia have increased ligand-mediated calcium responses, which are blocked by selective P2Y12 antagonism. P2Y12 antagonism was also shown to decrease migratory and inflammatory responses in human microglia upon exposure to nucleotides that are released during CNS injury; no effects were observed in human monocytes or macrophages. In situ experiments confirm that P2Y12 is selectively expressed on human microglia and elevated under neuropathologic conditions that promote T h2 responses, such as parasitic CNS infection.
1) Grand Rounds Einstein Inst. of Medicine October 2014 2) NY Academy of Sciences November 2014 3) University of California, Irvine December 2014
1. Patent on the use of miR-155 inhibitors as a therapy for ALS 2. BWH has filed a patent provisional application to use APOE inhibitors in ALS
MiRagen Therapeutics Research Award (Butovsky, PI)10/15/2013 ? 06/04/2015
NANCY DAVIS FOUNDATION FOR MS (Butovsky PI) 07/01/14 ? 06/30/15 National MS Society RG 5092A1/1 (Butovsky, PI) 10/01/14 ? 09/30/17 ALS Association ALS2087 (Butovsky, PI) 01/15/13 ? 01/14/15
Diogenix, Advisor, Scientific Board, 2008- Ono Pharmacia, Advisor, Scientific Board, 2008- Receptos, Advisor, Scientific Board, 2011 - Roche, Advisor, Scientific Board, 2008- Novartis, Advisor, Scientific Board, 2012- GSK, Advisor 2012 - Guthy Jackson Greater Good Foundation, Scientific Advisor,2008-
Diogenix, Advisor, Scientific Board, 2008- Ono Pharmacia, Advisor, Scientific Board, 2008- Receptos, Advisor, Scientific Board, 2011 - Roche, Advisor, Scientific Board, 2008- Novartis, Advisor, Scientific Board, 2012- GSK, Advisor 2012 -
Neurology, Editorial Board Member, 2008-Clinical and Experimental Neuroimmunology, Editorial Board Member, 2010 -
Diogenix, Advisor, Scientific Board, 2008- Ono Pharmacia, Advisor, Scientific Board, 2008- Receptos, Advisor, Scientific Board, 2011 - Roche, Advisor, Scientific Board, 2008- Novartis, Advisor, Scientific Board, 2012- GSK, Advisor 2012 -
Sanofi Aventis, TEVA Neuroscience, Biogen IDEC, Genzyme,Cleveland Clinic Foundation, Novartis
TEVA Neuroscience - travel to symposium + honorarium Novartis - travel to symposium + honoraraium EMD Serono -travel to symposium + honorarium BiogenIdec - travel to symposium + honorarium
Multiple Sclerosis Journal - editor for the Americas - 2006 GLIA - 1999 Journal Neuroimmunology - 1989 Journal of Neuroscience Research - 1991
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