Marlene Rabinovitch

Clinical Focus

• Cardiology (Heart), Pediatric
• Pediatric Cardiology

Administrative Appointments

• Director of Research, Vera Moulton Wall Center for Pulmonary Vascular Disease (2003 - present)

Honors and Awards

• Scientific Accomplishment Award, American Thoracic Society (2008)
• Distinguished Scientist Award, American Heart Association (2006)
• Dickinson Richards Lecture, American Heart Association (2005)
• Basic Research Prize, American Heart Association (2004)
• Leadership Award and Prize, CIHR-Institute of Circulatory & Respiratory Health (2004)

Professional Education

Postdoctoral Advisees

Tero-Pekka Alastalo , Yu-Mee Kim , Ying-Ju Lai , Hirofumi Sawada

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Developmental Biology
• Medicine

Community & International Work

• National Heart, Lung, Blood Institute Advisory Council, NIH, Bethesda, MD 
• Executive Committee, Pulmonary Vascular Research Institute (PVRI) 
• Canadian Institutes of Health Research, Circulatory and Respiratory Institute Advisory Board 
• Burroughs Wellcome Fund, Translational Research Advisory Committee 
• Pulmonary Hypertension Association, Scientific Advisory Board 

Web Site Links

• Rabinovich/Bland Lab

Research Interests

Our research focuses on the regulation of genes associated with cardiovascular development and disease. We identified a novel smooth muscle cell elastase that has a pivotal role in the pathobiology of pulmonary hypertension, vein graft atherosclerosis, transplant arteriopathy and rejection, coronary artery disease, restenosis, myocardial ischemia and myocarditis. Inhibition of elastase prevents or reverses the pathology in experimental animals. We are now pursuing fundamental studies which address the transcriptional regulation of elastase by AML1 and how this relates to genetic mechanisms of disease, focusing on polymorphisms in the serotonin transporter, mutations in a bone morphogenetic protein receptor, and overexpression of a calcium binding protein, Mts1. These studies use cultured cells, transgenic mice, gene arrays and gene therapy and are aimed at developing new treatments.

In our studies related to regulation of cell motility, a key feature of vascular pathology, we identified a requisite increase in production of the microtubule-associated protein LC-3, which is highly conserved across species. This protein regulates the efficiency of mRNA translation of genes, including fibronectin and apolipoprotein D. We determined that LC3, through its triple arginine motif, engages an AU rich element in the 3’ untranslated region of fibronectin mRNA, to enhance efficiency of mRNA translation. We are now addressing whether this process is critical to the regulation of a constellation of transcripts necessary for cell motility in development and disease. We are pursuing evidence that LC3 is regulated by nitric oxide, and are currently investigating how this leads to its phosphorylation and binding to mRNA. In addition, we are relating LC-3 to the migration of other cell types, including neural crest cells which regulate cardiac development, as well as neuronal cells, where it is highly expressed in development, and in diseased tissues and cancer cells. We...

Clinical Trials

• Insulin Resistance in Pulmonary Arterial Hypertension Recruiting

Publications

• S100A4 and bone morphogenetic protein-2 codependently induce vascular smooth muscle cell migration via phospho-extracellular signal-regulated kinase and chloride intracellular channel 4. Spiekerkoetter E, Guignabert C, de Jesus Perez V, Alastalo TP, Powers JM, Wang L, Lawrie A, Ambartsumian N, Schmidt AM, Berryman M, Ashley RH, Rabinovitch M. Circ Res. 2009; 105 (7): 639-47, 13 p following 647
• Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt-beta-catenin and Wnt-RhoA-Rac1 pathways. de Jesus Perez VA, Alastalo TP, Wu JC, Axelrod JD, Cooke JP, Amieva M, Rabinovitch M. J Cell Biol. 2009; 184 (1): 83-99
• Tie2-mediated loss of peroxisome proliferator-activated receptor-{gamma} in mice causes PDGF receptor-{beta}-dependent pulmonary arterial muscularization. Guignabert C, Alvira CM, Alastalo TP, Sawada H, Hansmann G, Zhao M, Wang L, El-Bizri N, Rabinovitch M. Am J Physiol Lung Cell Mol Physiol. 2009; 297 (6): L1082-90
• An antiproliferative BMP-2/PPARgamma/apoE axis in human and murine SMCs and its role in pulmonary hypertension. Hansmann G, de Jesus Perez VA, Alastalo TP, Alvira CM, Guignabert C, Bekker JM, Schellong S, Urashima T, Wang L, Morrell NW, Rabinovitch M. J Clin Invest. 2008; 118 (5): 1846-57
• SM22alpha-targeted deletion of bone morphogenetic protein receptor 1A in mice impairs cardiac and vascular development, and influences organogenesis. El-Bizri N, Guignabert C, Wang L, Cheng A, Stankunas K, Chang CP, Mishina Y, Rabinovitch M. Development. 2008; 135 (17): 2981-91