The Rabinovitch/Bland Lab Rabinovitch/Bland Cardiopulmonary Research Laboratory Hirofumi Sawada, MD, PhD, receives the 2011 AHA Cournand and Comroe Young Investigator Award in Cardiopulmonary and Critical Care Hirofumi Sawada, MD, PhD, is the 2011 recipient of the American Heart Association Cournand and Comroe Young Investigator Award for his work conducted during his post-doctoral fellowship with Dr Rabinovitch and entitled, “Reduced BMPR2 Increases GM-CSF mRNA Translation by Inhibiting eIF2α Mediated Stress Granule Formation and Propensity to Pulmonary Vascular Disease”. The co-authors are Drs. Alastalo, Glotzbach, Fuchs, Januszyk, Ms. R. Chan, Drs. Lai, de Jesus Perez, Saito, Spiekerkoetter, Wang, Gurtner, Sarnow, and Rabinovitch. Also at the 2011 AHA Annual Meeting, Dr. Marlene Rabinovitch was an invited speaker in a cardiovascular seminar on Emerging Therapeutic Targets in Pulmonary Hypertension, delivering a talk on “Inflammation as a Therapeutic Target for PAH”. Dr. Rabinovitch delivers the Inaugural Lois Taylor Ellison, MD, Lectureship in Physiology Dr Marlene Rabinovitch was the inaugural Lois Taylor Ellison, MD, Lecturer at the Georgia Health Sciences University in Augusta, GA on November 3, 2011. The lectureship was established by the Department of Physiology as a lasting tribute to Dr. Lois Taylor Ellison, a pioneer in Cardiopulmonary Medicine whose 60-plus-year affiliation with Georgia Health Sciences University has left a lasting legacy on the institution and on health care in general. The Lectureship will bring distinguished leaders in physiology to the Augusta campus, to exchange work and ideas with MCG researchers, while inspiring students and young investigators Summer 2011 Updates: NHLBI Translational Program Project Grant "Elafin Therapy of Lung Diseases" Awarded to a Team Led by Dr. Rabinovitch A research team led by Marlene Rabinovitch, MD, has been awarded a five-year, $10.8 million grant from the National Heart, Lung and Blood Institute for the study of a novel drug therapy’s ability to treat three distinct lung problems. The project was sparked by exciting preclinical data indicating that the elastase inhibitor elafin can be used to treat three of the most challenging lung conditions: pulmonary hypertension (project led by Dr Rabinovitch), ventilator-induced injury of the immature lung (led by Dr Bland) and lung transplant rejection (led by Dr. Mark Nicolls). A Biomarker Core, directed by Drs. Carlos Milla and Roham Zamanian, will develop bioassays to assess treatment efficacy for these diseases in humans and help stratify patients for future clinical trials. Read more: Inside Stanford Medicine story NHLBI Grant Awarded to Fund Use of iPS Cells to Study Pulmonary Hypertension Marlene Rabinovitch, Michael Snyder (Genetics) and Joe Wu (CV Medicine) were awarded $9.1 million over five years to study the inherited causes of pulmonary hypertension, using induced pluripotent stem cells (iPSCs) as surrogates for the disease. The team will create blood vessel cells from patients with pulmonary hypertension to explore the hereditary causes of the condition. Key to the study is a collaboration with the Pulmonary Hypertension Breakthrough National Network, which will enable the Stanford team to work with cells from diseased lungs that were removed during a transplant operation. The studies proposed will not only help uncover the genetic basis for pulmonary hypertension but will improve our understanding of the biological basis of the disease, which is necessary to develop diagnostic tools and personalized treatment strategies. Read more: Inside Stanford Medicine story Recently Featured Research - Commentaries, Covers, Media: Targeting elastase in Bronchopulmonary Dysplasia: The article "Inhibiting Lung Elastase Activity Enables Lung Growth in Mechanically Ventilated Newborn Mice" from the laboratory of Dr Richard Bland, was featured in an editorial in the American Journal of Respiratory and Critical Care Medicine. The author, Rory E. Morty, PhD, said: "In this issue of the Journal (pp. 537) Hilgendorff and coworkers (8) make the exciting observation that intratracheal administration of elafin ... concomitantly with mechanical ventilation of 5-day old full-term mouse pups with oxygen-rich (40% O2) gas protected against the deleterious effects of mechanical ventilation with oxygen-rich gas on alveolar development. The beauty of the experimental model ...is the extent of recapitulation of the clinical scenario: the mechanical ventilation of neonates during a critical phase of late lung development (in this case, the saccular stage), with relatively moderate levels of normobaric oxygen, compared with, for example, classical hyperoxia-based animal models of BPD, in which oxygen concentrations of 85 to 95% O2 are employed, without mechanical ventilation." BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways: The article was featured in the January 10, 2011 edition of Biobytes (The Rockefeller University Press). Vinicio de Jesus Perez and Marlene Rabinovitch describe the signaling pathways that regulate blood vessel repair. The article presents a novel cell-signaling paradigm in which bone morphogenetic protein 2 (BMP-2) consecutively and interdependently activates the wingless (Wnt)–ß-catenin and Wnt–planar cell polarity (PCP) signaling pathways to facilitate vascular smooth muscle motility while simultaneously suppressing growth. de Jesus Perez VA, et al., Journal of Cell Biology 2010; 192 (1): 171-188. Listen to the podcast: http://jcb.rupress.org/content/192/1/171/suppl/DC2 BMP-2 recruits the PDZ and DEP domains of Dvl to activate RhoA and Rac1 and induce hPAEC motility:
Mutations in the bone morphogenetic protein receptor (BMPRII) are associated with idiopathic pulmonary hypertension, which is characterized by a loss of pulmonary artery endothelial cells (PAECs). Bmpr1a deletion assessed by whole-mount LacZ staining: Cover Figure, Circulation Research, Vol. 102(3), February 15, 2008:
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Disruption of PPARgamma /ß-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival. Inhibiting Lung Elastase Activity Enables Lung Growth in Mechanically Ventilated Newborn Mice. Neutrophil elastase is produced by pulmonary artery smooth muscle cells and is linked to neointimal lesions. Inhibition of transforming growth factor ? worsens elastin degradation in a murine model of Kawasaki disease. BMP promotes motility and represses growth of smooth muscle cells by activation of tandem Wnt pathways.
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Patchy LacZ staining shown in pulmonary lobar vessels (left) and aorta (upper right) of the
SM22a;TRE-Cre;R26R; Bmpr1a flox/flox adult mutant mouse. This patchy staining was also seen in cardiovascular tissues of E11.5 mutant embryo as seen in the right atrium and ventricle of the heart (lower right). Associated with the article "
