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Stella  Kourembanas, MD

Stella Kourembanas MD
Department:
Medicine Research
Division
Newborn Medicine Research
Hospital Title:
Chief, Division of Newborn Medicine
Academic Title:
Clement A. Smith Professor of Pediatrics; Academic Chair, Harvard Program in Neonatology
Research Focus Area:
Lung vascular biology
Contact:
617-919-2355
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Research Overview

Dr. Kourembanas’ research program investigates the molecular and cellular basis of lung inflammation, hypoxic signaling, and developmental lung injury. Using various genetically-modified mouse models, her laboratory has been investigating the pathobiology of pulmonary hypertension and the transcriptional and epigenetic mechanisms by which hypoxia induces chemokine gene expression leading to lung inflammation and lung vascular remodeling.  An active area of research in the lab is the study of stem cell-based therapies, and in particular, the biology and application of mesenchymal stem cell exosomes as a novel therapeutic approach to the treatment of lung diseases including pulmonary hypertension and bronchopulmonary dysplasia. As a PI on several previous and current NIH-funded grants including a SCOR program, she has led several collaborative basic and translational studies that have contributed new knowledge to the field of lung biology.  Most notably, her group was among the first to demonstrate that inflammation plays a critical role in the development of pulmonary hypertension, an area that has recently received wide interest and has become a major focus of study by lung biologists investigating mechanisms of disease and therapeutic strategies targeting lung inflammation.  

Dr. Kourembanas has a long track record of mentoring scientists in lung biology for over 20 years, many of whom are successful independent investigators and program leaders in their own right. She also serves as Program Director of a NIH-funded T32 program training physician-scientists in neonatal-perinatal medicine since 2003.  She is an internationally-recognized expert on the biology of hypoxia and the investigation of stem cell therapies for the treatment of developmental and vascular diseases of the lung. She is an elected member to American Society for Clinical Investigation, the Pediatric Academic Societies, and the Society of Perinatal Research. She has given several State-of-the-Art, Keynote lectures, and named lectureships on her research discoveries at National and International Symposia and has served as standing member of NIH study sections on Lung Biology & Pathology (LBPA) and Respiratory Integrative Biology & Translational Research (RIBT), the Hood Foundation, and the Parker B. Francis Fellowship Program.  

About Stella Kourembanas

Dr. Kourembanas was raised in Brooklyn, New York and attended Barnard College.  She received her M.D. from New York University Medical Center and completed her residency in Pediatrics at Massachusetts General Hospital, Boston.  She subsequently completed a Fellowship in Neonatal-Perinatal Medicine in the Joint Program in Neonatology of Harvard Medical School, and was appointed to the Faculty of the same Program.  She rose through the ranks to Professor at Harvard Medical School, and in 2005, she was appointed Chief of Neonatology at Boston Children’s Hospital and Academic Chair of the Harvard Neonatal-Perinatal Medicine Program.

In addition to her teaching and administrative responsibilities, she is a full time clinical attending in the Neonatal Intensive Care Unit providing care to critically-ill infants.  She has also been the recipient of two teaching awards from the Harvard Programs for excellence in clinical teaching and for mentoring the career development of Pediatric Residents (Janeway Award) and Neonatology Fellows (Bernfield Award). In particular, the Charles A. Janeway Teaching Award is considered the most prestigious distinction for teaching at Boston Children’s Hospital.

Key Publications

1.    Morita T and Kourembanas S.  Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide.  J. Clin. Invest. 1995;96:2676-2682.  PMCID: PMC185974.
2.    Liu Y, Christou H, Morita T, Laughner E, Semenza GL and Kourembanas S.  Carbon monoxide and nitric oxide suppress the hypoxic induction of vascular endothelial growth factor gene via the 5' enhancer. J. Biol. Chem. 1998;273(24):15257-15262.
3.    Yet S-F, Perrella M, Layne MD, Hsieh C-H, Maemura K, Kobzik L, Wiesel P, Christou H, Kourembanas S, Lee M-E.  Hypoxia induces severe right ventricular dilatation and infarction in heme oxygenase-1 null mice. J.Clin.Invest. 1999;103:R23-R29.  PMCID: PMC408281.
4.    Minamino T, Mitsialis, SA, Kourembanas S.  Hypoxia extends cell lifespan of vascular smooth muscle cells through telomerase activation. Mol. Cell Biol. 2001;21(10):3336-3342.  PMCID: PMC100255.
5.    Minamino T, Christou H, Hsieh C-M, Liu Y, Dhawan V, Abraham NG, Perrella MA, Mitsialis SA, Kourembanas S.  Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia. Proc. Natl. Acad. Sci. USA 2001;98(15):8798-8803.  PMCID: PMC37515.
6.    Wu X, Chang M S., Mitsialis S.A., Kourembanas S. Hypoxia regulates bone morphogenetic protein signaling in vascular smooth muscle cells through CtBP-1. Circ. Res. 2006; 99:240-247.
7.    Aslam M, Baveja R, Liang OD, Fernandez-Gonzalez A, Lee C, Mitsialis SA, Kourembanas S. Bone   marrow stromal cells attenuate lung injury in a murine model of neonatal chronic lung disease. Am. J. Respir. Crit. Care Med. 2009;180(11):1122-30.  PMCID: PMC2784417.
8.    Liang OD, Mitsialis SA, Chang MS, Vergadi E, Lee C, Aslam M, Fernandez-Gonzalez A, Liu X, Baveja R, Kourembanas S. Mesenchymal stromal cells expressing heme oxygenase-1 reverse pulmonary hypertension. Stem Cells 2011;29(1):99-107.  PMCID:PMC3422740.
9.    Vergadi E, Chang MS, Lee C, Linag OD, Liu X, Fernandez-Gonzalez A, Mitsialis SA, Kourembanas S. Early Macrophage Recruitment and Alternative Activation Are Critical for the Later Development of Hypoxia-induced Pulmonary Hypertension.  Circulation 2011;123(18):1986-95. PMCID: PMC3125055.
10.    Fernandez-Gonzalez A, Mitsialis SA, Liu X, Kourembanas S. Vasculoprotective effects of heme oxygenase-1 in a murine model of hyperoxia-induced bronchopulmonary dysplasia. Am. J. Physiol. Lung Cell Mol. Physiol. 2012;302(8):L775-84.  PMCID:PMC3331581.
11.    Christou H, Reslan OM, Mam V, Tanbe AF, Vitali SH, Touma M, Arons E, Mitsialis SA, Kourembanas S, Khalil RA. Improved Pulmonary Vascular Reactivity and Decreased Hypertrophic Remodeling during Non-Hypercapnic Acidosis in Experimental Pulmonary Hypertension. Am. J. Physiol. Lung Cell Mol. Physiol. 2012;302:L875-90.  PMCID: PMC3362160
12.    Hansmann G, Fernandez-Gonzalez A, Aslam M, Vitali SH, Martin T, Mitsialis SA, Kourembanas S. Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and associated pulmonary hypertension. Pulm. Circ. 2012;2(2):170-81.  PMCID:PMC3401871.
13.    Lee C, Mitsialis SA, Aslam M, Vitali SH, Vergadi E, Konstantinou G, Sdrimas K, Fernandez-Gonzalez A, Kourembanas S.  Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension.  Circulation 2012;126(22):2601-11.  PMCID: PMC3979353.
14.    Xiao Y, Christou H, Liu L, Visner G, Mitsialis SA, Kourembanas S, Liu H. Endothelial indoleamine 2,3-dioxygenase protects against development of pulmonary hypertension. Am J Respir Crit Care Med. 2013;188(4):482-491. PMCID:PMC3778740.
15.    Sdrimas K, Kourembanas S.  MSC Microvesicles for the Treatment of Lung Disease: A New Paradigm for Cell-Free Therapy. .Antioxid Redox Signal. 2014 Feb 24. [Epub ahead of print].
16.    Kourembanas S. Stem Cell-Based Therapy for Newborn Lung and Brain Injury: Feasible, Safe, and the Next Therapeutic Breakthrough? J Pediatr. 2014;164(5):954-6.
17.    Kourembanas S. Expanding the pool of stem cell therapy for lung growth and repair. Circulation.  2014;129(21):2091-3. PMCID: PMC4063347
18.    Hale A, Lee C, Annis S, Min PK, Pande R, Creager MA, Julian CG, Moore LG, Mitsialis SA, Hwang SJ, Kourembanas S, Chan SY.  An Argonaute 2 switch regulates circulating miR-210 to coordinate hypoxic adaptation across cells. Biochim Biophys Acta. 2014;1843(11):2528-2542.

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