Simon Christopher Robson, PH.D., M.B.CH.B.
|Title||Charlotte F. and Irving W. Rabb Professor of Medicine|
|Institution||Beth Israel Deaconess Medical Center|
|Address||Beth Israel Deaconess Medical Center|
C L S 612
330 Brookline Ave
Boston MA 02215
Available: 10/07/13, Expires: 09/30/14
The research interests in my laboratory are in purinergic signaling and we focus on the vascular and immune ectonucleotidases of the CD39 family. These signaling pathways are crucial in modulating inflammation and immune responses in the liver and gastrointestinal tract, such as in inflammatory bowel disease (IBD), non alcoholic steatohepatitis (NASH) and liver fibrosis.
We have identified ectonucleotidase activity in the vasculature and immunoregulatory cells and confirmed that CD39 has identity with the ATP or nucleoside triphosphate diphosphohydrolase (EC 18.104.22.168; ENTPD1). We have developed Cd39-deficient and CD39 transgenic mice and pigs. Over expression of CD39 in transgenic vasculature and immune cells has demonstrated substantive benefits in allo and xenograft functions. Modulation of CD39 impacts survival and in models of inflammation and hepatic/intestinal fibrogenesis.
Recent work has detailed the functional consequences of plasma membrane expression of CD39 and related family members by dendritic cells, regulatory T cells, T helper type 17 (Th17) and natural killer T (NKT) cells.
The proposed HMS scholarly project will be as follows:
To define the mechanism of purinergic signaling in regulation of macrophage activation and generation of pro-fibrogenic stimuli in mouse liver models of liver injury.
Phenotype of of CD39-deficient and wildtype macrophages will be studied in vitro and in co-culture with hepatic stellate cells in presence of exogenous ATP/adenosine. Identification of ATP receptor which mediate hyper-inflammatory responses in absence of Cd39 will be studied (P2X7) using chemical inhibitors and siRNA screens. Putative fibrogenic/fibrolytic soluble mediators released by macrophages in response to ATP/Adenosine will be identified in macrophage/HSC co-culture system using neutralizing antibodies.
Full details and preliminary data are available on request.
The role of CD39 in the modulation of effector/regulatory cell balance in inflammatory bowel disease
Summer, 06/11/12 - 09/07/12
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