Marlene Rabinovitch
Academic Appointments
- Professor, Pediatrics - Cardiology
- Member, Bio-X
Key Documents
Contact Information
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Clinical Offices
Stanford University School of Medicine 269 Campus Drive CCSR, Room 1215A, MC: 5162 Stanford, CA 94305 Tel Work (650) 723-8239 Fax (650) 723-6700Practices at Stanford Hospital and Clinics and Lucile Packard Children's Hospital
- Academic Offices
Personal Information EmailAlternate Contact Administrative Associate Email Tel Work 723-8239Not for medical emergencies or patient use
Professional Overview
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
- Louis and Artur Lucian Award for Research in Circulatory Diseases, McGill University (2010)
- 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
| Residency: | University of Colorado Health Science Center CO (1973) |
| Board Certification: | Pediatric Cardiology, American Board of Pediatrics (1979) |
| Fellowship: | Children's Hospital, Harvard Medical School MA (1977) |
| Board Certification: | General Pediatrics, American Board of Pediatrics (1976) |
| Internship: | University of Colorado Health Science Center CO (1972) |
| Medical Education: | McGill University, Canada (1971) |
Postdoctoral Advisees
Pin-I Chen, Isabel Diebold, Nancy Ferreira Tojais, Jan Hennigs, Caiyun Li, Nils Nickel, Toshie Saito
Graduate & Fellowship Program Affiliations
Community and 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, International
- Burroughs Wellcome Fund, Translational Research Advisory Committee, International
- Pulmonary Hypertension Association, Scientific Advisory Board, US
Internet Links
Scientific Focus
Current 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 are utilizing transgenic mice, RNAi, and transcriptional profiling by DNA microarray approaches to investigate the impact of LC3-dependent mRNA translation on cell function.
We have also cloned a novel chymase that mediates enhanced experimental hypertension through processing angiotensin II, endothelin 1, and transforming growth factor beta.
Our research program harmonizes with that of Dr. Richard Bland who investigates the regulation, expression and function of genes that coordinate pulmonary alveolar and vascular development, and how they are perturbed by prematurity and mechanical ventilation, leading to chronic lung disease.
Publications
- Loss of adenomatous poliposis coli-α3 integrin interaction promotes endothelial apoptosis in mice and humans. Circ Res. 2012; (12): 1551-64
- BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways. J Cell Biol. 2011; (1): 171-88
- Disruption of PPARγ/β-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival. J Clin Invest. 2011; (9): 3735-46
- Inhibition of transforming growth factor β worsens elastin degradation in a murine model of Kawasaki disease. Am J Pathol. 2011; (3): 1210-20
- Neutrophil elastase is produced by pulmonary artery smooth muscle cells and is linked to neointimal lesions. Am J Pathol. 2011; (3): 1560-72
- Bone morphogenetic protein 2 induces pulmonary angiogenesis via Wnt-beta-catenin and Wnt-RhoA-Rac1 pathways. J Cell Biol. 2009; (1): 83-99
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