Marlene Rabinovitch, M.D.
June 1, 2020
Dwight and Vera Dunlevie Professor of Pediatrics (Cardiology)
Stanford University School of Medicine
Our research program seeks to identify the cellular and molecular programs that are dysregulated in vascular disease with a focus on pulmonary arterial hypertension (PAH). This condition can be a fatal complication in children with heart defects, but can also arise as a complications of pulmonary and hepatic disorders, sickle cell disease, including infectious and autoimmune disease, and drugs and toxins. It cab also occur as a potentially fatal disease of unknown etiology affecting all age groups but seen with 2:1 ratio in young women compared to men. The familial form of PAH has been attributed largely to a mutation in BMPR2. PAH is characterized by progressive loss and occlusion of the distal pulmonary microcirculation, and is associated with endothelial dysfunction, exuberant proliferation of de-differentiated smooth muscle-like cells, and chronic perivascular inflammation, all contributing to increased resistance to flow and culminating in heart failure. There are treatments for PAH that improve survival and quality of life. However these therapies primarily dilate blood vessels and do not cure PAH because they do not alter the underlying pathological mechanisms that cause the obliteration of the lung blood vessels. Our studies use high throughput genomic technologies, a variety of cell biology platforms including confocal and videomicroscopy, genetically modified mouse models of human disease, human tissue samples from lung and blood and induced pluripotent stem cells differentiated to vascular cells to learn how we can activate molecular programs to regenerate lost microvessels and to reverse the obliterative changes. Over the past decade our research has led to two novel compounds in clinical trial, the elastase inhibitor human recombinant elafin has successfully completed a Phase I clinical trial and low dose FK-506 is slated for an expanded Phase II clinical trial.
Laboratory Website: http://med.stanford.edu/rabinovitchbland.html
Members of the laboratory:
Jen Lingli Wang, MD - Senior Scientist, Lab Manager
Aiqin Cao, PhD - Basic Life Science Research Associate
Jan-Renier Moonen, MD, PhD - Postdoc
Shalina Taylor, PhD - Postdoc
Shoichiro Otsuki, MD - Postdoc
Dan Li, PhD - Postdoc
Sarasa Isobe, MD - Postdoc
Marcy Martin, PhD - Postdoc
David Marciano, PhD - Postdoc
Rebecca Harper, PhD - Postdoc
Tstuomu Shinohara, MD - Visiting Clinical Professor
Michelle Fox: Project Director
Michal Roof, PhD: Academic Program Officer
- Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension. Reyes-Palomares A, Gu M, Grubert F, Berest I, Sa S, Kasowski M, Arnold C, Shuai M, Srivas R, Miao S, Li D, Snyder MP, Rabinovitch M, Zaugg JB.Nat Commun. 2020 Apr 3;11(1):1673. doi: 10.1038/s41467-020-15463-x.
- PPARγ Interaction with UBR5/ATMIN Promotes DNA Repair to Maintain Endothelial Homeostasis. Li CG, Mahon C, Sweeney NM, Verschueren E, Kantamani V, Li D, Hennigs JK, Marciano DP, Diebold I, Abu-Halawa O, Elliott M, Sa S, Guo F, Wang L, Cao A, Guignabert C, Sollier J, Nickel NP, Kaschwich M, Cimprich KA, Rabinovitch M.Cell Rep. 2019 Jan 29;26(5):1333-1343.e7. doi: 10.1016/j.celrep.2019.01.013.PMID: 30699358
- Smooth Muscle Contact Drives Endothelial Regeneration by BMPR2-Notch1-Mediated Metabolic and Epigenetic Changes. Miyagawa K, Shi M, Chen PI, Hennigs JK, Zhao Z, Wang M, Li CG, Saito T, Taylor S, Sa S, Cao A, Wang L, Snyder MP, Rabinovitch M.Circ Res. 2019 Jan 18;124(2):211-224. doi: 10.1161/CIRCRESAHA.118.313374.PMID: 30582451