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Mohamad Bouhamdan, Ph.D.
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RESEARCH INTERESTS:
During the last decade, Regulator of G protein Signaling (RGS) proteins have emerged as important regulators of cell to cell signaling. Work to date has identified more than 30 RGS proteins which can be classified in at least 9 groups based upon sequence and domain structure. These proteins are expressed in most mammalian tissues but are particularly well expressed in the CNS where they are presumed to regulate neuronal signaling.
Our investigations focus on understanding the role and function of one of the RGS family member, the RGS9-2, which is expressed in the brain. We study the subcellular localization of RGS9-2 by using immunofluorescence, immunohistochemistry, biololistic approaches, and western blotting techniques. Using the yeast two hybrid system, we identify some candidates which interact with RGS9-2. This screen identified a strong interaction between RGS9-2 and a-actinin-2 and suggests a potential novel role for RGS9-2 in the regulation of NMDA receptor function. The variety of interactions with RGS9-2 mediated by these candidates may explain the different effects this RGS9-2 protein have on cellular functions.
We also are using viral vectors like AAV and HSV as a tool to deliver genes of interest into different regions of the brain. We showed that GFP and beta-gal could be expressed in different regions of the brain by using the AAV and HSV delivery systems respectively. Further investigations in understanding the role of RGS9-2 in neuropsychiatric conditions (including Parkinson’s disease, schizophrenia, attention deficit disorder and drug abuse) thought to involve dysfunction of forebrain dopamine neurotransmission have also been undertaken.
Transfection of striatal MSNs using an HSV viral vector. A. Low power photomicrograph illustrating a striatal transfection using an HSV virus expressing LacZ. Blue product indicates robust cellular β-galactosidase expression (including darker labeled somata-arrows) after reaction with Xgal. Calibration bar: 250 mm. * corticofugal fiber bundle. B. Immunolocalization of DARPP32 and β-galactosidase in striatum. B1, DARPP32 immunoreactivity visualized using confocal microscopy. B2, β-galactosidase immunoreactivity in the same section. B3, overlay of the sections illustrated in B1 and B2.
Selected Publications:
Mohamad Bouhamdan, Hai-Dun Yan, Xiu-Hua Yan, Michael Bannon, and Rodrigo Andrade. Brain-specific RGS9-2 selectively interacts with a-actinin-2 to regulate calcium-dependent inactivation of NMDA receptors. (2006) Journal of Neuroscience. 26 (9): 2522-2530.
Michelhaugh SK, Vaitkevicius H, Wang J, Bouhamdan M, Krieg AR, Walker JL, Mendiratta V, Bannon MJ. Dopamine neurons express multiple isoforms of the nuclear receptor nurr1 with diminished transcriptional activity. (2005) J. Neurochem. 95(5):1342-50.
Sin M, Walker PD, Bouhamdan M, Quinn JP, Bannon MJ. Preferential expression of an AAV-2 construct in NOS-positive interneurons following intrastriatal injection. (2005) Brain Res Mol Brain Res. 141(1):74-82.
Mukhtar M, Acheampong E, Khan MA, Bouhamdan M, Pomerantz RJ. Down-modulation of the CXCR4 co-receptor by intracellular expression of a single chain variable fragment (SFv) inhibits HIV-1 entry into primary human brain microvascular endothelial cells and post-mitotic neurons. Brain Res Mol Brain Res. 2005 Apr 27;135(1-2):48-57.
Mohamad Bouhamdan, Sharon K. Michelhaugh, Irina Calin-Jageman, Shawn Ahern-Djamali and Michael J. Bannon. Brain-Specific RGS9-2 is Localized to the Nucleus Via Its Unique Proline-Rich Domain (2004). Biochem. Biophys. Acta- Mol. Cell Res. 1691, 141-150.
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