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Department of Cell Biology Faculty

Dr. Mohamed Boutjdir

Mohamed Boutjdir, Ph.D.

Professor, SUNY Downstate

Associate Chief of Staff for Research & Development

New York Harbor Health Care System (VAMC)

Tel: (718) 630-3645 • Fax: (718) 630-3796

e-mail: mohamed.boutjdir@med.va.gov

1. Pathogenesis of Autoimmune Associated Congenital Heart Block
2. Autonomic Control of Cardiac Function

Congenital heart block (CHB) is a heart conduction defect that affects fetuses and infants of mothers with autoimmune disease. The ultimate goal of our research program is to understand the electrophysiologic mechanisms of CHB and develop novel therapeutic approaches, which may reverse or prevent CHB through fundamental observations at the bench. In addition, our research interest expands to the pathophysiology of central nervous system control of cardiac function through complex signaling cascades. Experiments are conducted in transgenic animal models, isolated single cardiac myocytes and heterologous expression systems. State of the art electrophysiological, biochemical, imaging and molecular techniques are used.

Project#1
CHB is strongly associated with the intracellular soluble ribonucleoproteins 48kD SSB/La, 52kD SSA/Ro, and 60kD SSA/Ro. CHB is presumed to be due to the transplacental passage of autoantibodies from the mother into the fetal circulation. CHB carries substantial mortality and morbidity, with > 60% of affected children requiring lifelong pacemakers. Curiously, the mother's heart is almost never affected despite exposure to identical circulating autoantibodies. We have established an animal model of CHB and reproduced the human complete AV block in an isolated Langendorff perfused fetal heart. These findings were correlated with maternal anti-Ro/La antibodies' inhibition of L-type Ca channel. Alterations in Ca channel function often lead to abnormal electrical activity and arrhythmias.

Project#2
In the heart, sarcolemmal ion channels are responsible for the generation and control of the action potential. Thus, alterations in channel function often lead to abnormal electrical activity and arrhythmias. Three major voltage-gated ion channels, Ca, Na, and K channels are under the control of autonomic nervous system.

Our efforts are directed at characterizing the pathways involved in this control and dissecting the exact signaling mechanisms responsible for this modulation. To date we have been able to pinpoint to the functional role of individual PKC isozymes in the regulation of ion channels by the use of highly specific peptides PKC isozyme activators and inhibitors.


SELECTED RECENT PUBLICATIONS

1. Qu Y, Baroudi G, Yue Y, Boutjdir M: A Novel Mechanism Involving alpha-1D (Cav1.3) L-type Ca Channel in Autoimmune-Associated Sinus Bradycardia. Circulation. Jun 14; 111(23):3034-41. Epub 2005.

2. Qu Y, Baroudi G, Yue Y, Boutjdir M: Localization and Modulation of Alpha1D (Cav1.3) L-type Ca Channel by Protein Kinase. A. Am J Physiol Heart Circ Physiol. May; 288(5):H2123-30, 2005.

3. Hu K, Qu Y, Boutjdir M: Functional Basis of Sinus Bradycardia in Congenital Heart Block. Circ Res 94: E32-8, 2004.

4. Vijayaragavan S, Boutjdir M and Chahine M: Modulation of Nav1.7 and Nav1.8 Nerve Sodium Channels by Protein Kinase A and Protein Kinase C. J Neurophysiol. 91: 1556-69, 2004.

5.Chie L, Qu Y, Chung D, Boutjdir M, Pincus RM: Oncogenic and Activated Wild-Type ras-p21 Proteins Induce Different Isoforms of Protein Kinase C in Mitogenic Signal Transduction. Protein Chemistry 22: 625-9, 2003.

6. Xiao G, Daria Mochly-Rosen, Boutjdir M: Up regulation of cloned human Delayed rectifier K channel by PKC isoforms. Biochem Biophys Res Commun. Jul 11; 306(4):1019-25, 2003.

7. Buyon J, Di Donato F, Miranda E, Askanase AD, Garcia J, Chan EKL, Boutjdir M: Cardiac 5-HT4 Serotoninergic Receptors, 52kD SSA/Ro and Autoimmune-Associated Congenital Heart Block. J Autoimmun. Aug; 19(1-2):79, 2002.

8. Xiao G, Hu K, Boutjdir M: Evidence for functional role of ePKC isozyme in the regulation of Cloned Human cardiac Na channels. Am J Physiol Cell Physiol. Nov; 281(5):C1477-86, 2001.

9. Qu Y, Boutjdir M: Gene Expression of SERCA2, L- and T-type Ca channels during Development in Human Fetal Heart. Pediatr Res. Nov; 50(5):569-74, 2001.

10. Qu YX, Chen L, Xiao G, Boutjdir M: Autoantibodies from Mothers of Children with Congenital Heart Block Directly Crossreact and Downregulate Cardiac L-Type Ca channels. J Mol Cell Cardiol. Jun; 33(6):1153-63, 2001.

11. Qu YX, Chen L, Xiao G, Boutjdir M: Autoantibodies from Mothers of Children with Congenital Heart Block Directly Crossreact and Downregulate Cardiac L-Type Ca channels. J Mol Cell Cardiol. Jun; 33(6):1153-63, 2001.

List of Publications (Pub Med)

* Holds primary appointment in other department.