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Postdoctoral Training

Postdoctoral opportunities are available for young scientists interested in pursuing research in pulmonary vascular disease. We pride ourselves on developing outstanding scientists who are positioned to become the next generation of thoughtful leaders in pulmonary vascular disease.

 

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Summer Students

We offer Summer Internships for graduate, undergraduate and high school students interested in a career in medicine or science. The goals of our program include increasing interest in biological sciences and medicine, helping students to understand how scientific research is performed, and increasing diversity of students and researchers in the sciences.

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Our Research Funding

Dr. Rabinovitch supported by the Dwight and Vera Dunlevie endowed Professorship. Our research funding includes grants from the National Institutes of Health, and from research foundations in the USA and abroad.

NIH Funding

Pulmonary Hypertension in Genetically Modified Mice (NIH/NHLBI grant R01 HL074186)

Funding period: 04/2004 – 01/2023

Principal Investigator: Marlene Rabinovitch

Collaborators: Mark R Nicolls and Michael P Snyder

Major goals:  This is the fourth period of this grant.  The application builds upon our recent studies indicating that aldehyde dehydrogenase (ALDH) enzymes can be critical metabolic switches that link chromatin remodeling with gene expression in vascular and inflammatory cells, and that the dysregulation of specific ALDH isoforms is linked in the pathogenesis of pulmonary arterial hypertension (PAH).

The BMP-PPARg Axis and Pulmonary Hypertension (NIH/NHLBI grant R01 HL087118)

Funding period: 12/2006 – 04/2023

Principal Investigator: Marlene Rabinovitch

Collaborator: Michael P Snyder

Major goals:  This third cycle of this grant builds upon our observation that In PAH PAEC, high IL6 levels are directly related to the phosphorylation of PPAR and its impaired interaction with MRN and UBR5, causing elevated ATMIN and impaired DNA damage sensing via phosphoATM.  These studies should provide a major inroad into understanding the molecular and functional sequelae of unrepaired DNA in vascular disease and their potential for reversibility of disease.

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Endothelial Injury, BMPR2 Dysfunction and Macrophage Activation Cause EndMT and PAH (NIH/NHLBI grant R01 HL138473)

Funding period: 07/2017 – 04/2021 (No-cost extension to 04/30/202; Renewal application pending)

Principal Investigators: Marlene Rabinovitch and Mark R Nicolls

Collaborator: Maria Ariza, The Ohio State University

Major Goals: This proposal addresses the hypothesis that injured PAECs with dysfunctional BMPR2 signaling recruit and activate macrophages that amplify LTB4 and HERV-K; these immune factors work in concert to sustain inflammation and promote severe PAH by apoptosis and EndMT.

 

Elafin Therapy for Pulmonary Arterial Hypertension (NIH/NHLBI Grant P01 HL108797)

Funding Period:  08/2011 – 06/2022

Principal Investigator: Marlene Rabinovitch

Clinical Project PI: Roham T Zamanian, MD

Advanced Proteomics Phenotyping Core: Garry P Nolan, PhD and Wendy Fantl, MD

Major goals:  This is a competitive renewal of our Program Project “Elafin Therapy for Lung Diseases”.  This Cycle II translational (t)PPG builds on the success of Cycle I with a focus on PAH, pursuing pre-clinical data indicating that the endogenous neutrophil elastase inhibitor, elafin, is a highly effective therapy for three challenging lung conditions.  Project 1 (Rabinovitch) investigates the mechanism explaining elevation in elastase protein and elastase activity in PAH neutrophils and addresses how recombinant human elafin, an elastase inhibitor with multiple other anti-inflammatory functions interacts with proteins in the intracellular space to suppress aberrant neutrophil function and uses high throughput technology to address the role of neutrophils in the inflammatory and vascular milieu in PAH patient tissues.  Project 3 relates specifically to the preclinical and clinical development of elafin to address toxicity and pharmacokinetics.  An Applied Proteomics Phenotyping Core and an Administrative Core coordinate bioassays, patient database and physiological studies.

 

High Shear Stress Alters Gene Regulation in Pulmonary Arterial Hypertension (NIH/NHLBI grant R01 HL152134)

Funding period: 01/2021-12/2024

Principal Investigator: Marlene Rabinovitch

Collaborators: Jesse Engreitz, Mark Skylar-Scott

Major goals:  This proposal tests the hypothesis that changes in PAEC and PAEC-SMC interaction in response to high shear stress (HSS) adversely impact the enhancer landscape, gene regulation and function, and can be reversed to prevent progressive PAH pathology.  These studies should provide new avenues for intervention to reverse disease by subverting the root cause of HSS mediated-progressive PAH.

 

Stanford Center for Connecting DNA Variants to Function and Phenotype (NIH/NHGRI grant UM1 HG011972)

Funding Period: 09/2021-05/2026

Principal Investigator: Jesse Engreitz

Role: Co-Investigator

Major goals:  The goals of this Impact of Genome Variation on Function (IGVF) Functional Characterization Center are to link genome wide functional variation and enhancer elements to specific genes and to cellular functions and related disease associations. Dr. Rabinovitch will contribute to variant and element selection, collaborate to validate endothelial cell differentiations, and supervise the phenotypic screens in endothelial cells.

 

R38 Stanford Integrated Cardiovascular/Pulmonary Residency Research Training Program (NIH/NHLBI grant R38 HL143615)

Funding Period: 02/2020 - 01/2024

Principal Investigator: Joseph C. Wu

Role: Co-Investigator

Major goals:  This grant seeks to train medical and surgical residents in the areas of cardiovascular and pulmonary research disciplines.

 

Recently completed NIH-funded projects:

Integrative Omics as a Discovery Tool for Pulmonary Hypertension (NIH/NHLBI grant R01 HL122887)

Funding period: 08/2015 – 05/2019

Principal Investigators: Marlene Rabinovitch, Mark R Nicolls and Michael P Snyder

Collaborator: Purvesh Khatri

This project develops and applies innovative bioinformatics methods of analysis to integrate very large publicly available data sets with novel data sets derived from state-of-the-art transcriptomic and metabolomic technologies, to generate a powerful systems biology approach to characterize pulmonary arterial hypertension (PAH).

 

Pulmonary Hypertension Breakthrough Initiative - Stanford Transplant Preparation Center (NIH/NHLBI Grant R24 HL123767)

Funding period: 09/15/14 – 06/30/19 (no-cost extension to 2021)

Principal Investigator: Mark Geraci, Indiana University, Indianapolis, IN (Prime: NIH/NHLBI)

Stanford Principal Investigator: Marlene Rabinovitch

Stanford Center co-Director: Roham Zamanian, MD

This project is to leverage the resources and unique expertise developed by the Pulmonary Hypertension Breakthrough Initiative (PHBI) Network under funding by the AHA-CMREF, into an NIH-supported initiative to accrue specimens of disease-specific groups, which was highly integrated with pathologic, genetic, and genomic sub-phenotypes pertaining to lung and blood specimens, and expanding to the failing pulmonary arterial hypertension (PAH) heart. Since its establishment in 2006, the PHBI successfully developed a novel and unique infrastructure, whose success relied on the active participation of a highly integrated network of university-based sites with extensive expertise in each of the spheres of competency: excellence in clinical care of PAH (including patient accruals), lung transplantation, pathology, genetics, genomics, and cell isolation. The Stanford Transplant Preparation Center was charged with the harvest and preparation of the explanted lung and heart for processing in accordance with the Network’s protocols, in such a manner that it will be useful to investigators of the PHBI Network for the broadest spectrum of studies.

 

Research Training Award:  Stanford Career Development Program in the Omics of Lung Diseases  (NIH/NHLBI grant K12 HL120001)

Funding period: 09/2013 – 05/2019

Principal Investigators: Marlene Rabinovitch, Mark R Nicolls, Michael P Snyder

This is a Career Development Program (CDP) in ‘Omics’ of lung diseases with a major focus on pulmonary arterial hypertension (PAH).  This is an extension of the successful Stanford K12 CDP on the “Genetics and Genomics of Lung Diseases” that focuses on PAH. The new CDP proposal allows us to equip the next cadre of MD and PhD scientists with interdisciplinary and bioinformatic skills to integrate new high throughput genomic, proteomic and metabolomic platforms to gain a better understanding of disease pathophysiology.

 

iPSC Derived EC as Surrogates Using Pulmonary Hypertension as a Prototype Disease (NIH/NHLBI grant U01 HL107393)

Funding period: 07/2011 06/2017

Principal Investigators: Marlene Rabinovitch, Michael P Snyder, Joseph C Wu

This project compared native pulmonary arterial PAECs from idiopathic pulmonary hypertensive (PAH) vs. control lungs to ECs transformed from induced pluripotent stem cells (iPSCs) that were derived from skin fibroblasts. We investigated gene variants by Exome and whole genome sequencing, DNA methylation by Methyl-Seq and RNA expression by RNA-Seq.  We then related these data to cell phenotype as assessed by angiogenesis assays. This study showed the efficacy of fibroblast-iPSC-ECs as surrogates for native pulmonary arterial endothelial cells (PAEC) in that they showed similar abnormalities when derived from patients with PAH. We then used the fibroblast iPSC-ECs to study correction of function by gene therapy or pharmaceutical agents identified by high throughput screening. They were also used to study the mechanism protecting subjects that were carriers of the BMPR2 mutation from developing PAH.

 

Other Funding for Current Research Projects

Our post doctoral fellows and visiting professors are supported by various agencies, with supplemental funding from the respective NIH/NHLBI grants above.

Sarasa Isobe, MD, PhD is supported by a Research Fellowship from the Japan Society for the Promotion of Science. She was previously supported by a postdoctoral fellowship from the American Heart Association (AHA), and by the MSD Life Science Foundation, Public Interest Incorporated Foundation Fellowship Program.

David Marciano, PhD, is funded by an NIH/NHLBI K99 Pathway to Independence award and was previously supported by an Individual NRSA post-doctoral fellowship (grant F32 HL132452).

Jan-Renier (JR) A J Moonen, MD, PhD is funded by a fellowship from the Tobacco-Related Disease Research Program (TRDRP). He was previously funded by The Netherlands Heart Foundation Grant 2013T116

Jason Szafron, PhD, is supported by the Parker B. Francis Fellowship for pulmonary and critical care research.

Funding for our Summer Interns is provided by various sources, including the Stanford Institutes for Summer Research (SIMR), the American Heart Association (AHA), the NIH/NHLBI, and the students’ undergraduate institutions (eg, in the past few years, Claremont McKenna College, Whitman College, SURF program at UC San Diego)

 

 

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