2025 Highlights
Two New Grants Were Awarded:
- A Phase 2 Study of Elafin in PAH
The NIH/NHLBI has awarded Stanford CVI Professors Marlene Rabinovitch and Roham Zamanian a 5-year, $12.5M grant for their proposal for “A Phase 2 Study of Elafin (Tiprelestat) for the Treatment of Pulmonary Arterial Hypertension (PAH)”. The Data Coordinating Center for the trial, led by Dr. Cathie Spino at the SABER unit at the University of Michigan, was funded by a companion application.
PAH is a disease of progressive obliteration of the lung vasculature that results from elastase mediated degradation of elastin, endothelial dysfunction, smooth muscle cell proliferation and chronic peri- and intravascular inflammation. There is an unmet need to find a therapy that is disease modifying in that it addresses these underlying cellular and molecular features of PAH. This proposal tests the safety and efficacy of human recombinant Elafin (tiprelestat) as a treatment for PAH in a randomized placebo-controlled clinical trial across 10 centers. Elafin is ideally suited for this role as it inhibits neutrophil elastase, suppresses cytokine mediated inflammation, and activates BMPR2 receptor signaling resulting in favorable profile of gene expression in hereditary and other forms of PAH. Beyond the primary endpoint of pulmonary vascular resistance (PVR) and numerous secondary endpoints, the study will evaluate the potential for disease modification – a “first-ever” in the field in PAH Clinical Trials. Beyond the clinical study enrolling centers, the study involves collaborations with three major cores: Harvard University for non-invasive pulmonary vascular imaging and blood volume quantification, UCSF for PK/PD modeling & assessments, and Temple University as the investigational pharmacy.
What makes this proposal even more special is that it is based on the life-long work of Dr. Marlene Rabinovitch and her leadership in investigating the role of elastase inhibitors in vascular diseases and their pleotropic impact on beneficial BMPR2 mediated gene regulation, combined with the leadership of Dr. Roham Zamanian in clinical investigation and clinical trials for new and promising PAH therapies.
- A Program Project Grant (PPG) to Identify Causal Gene Programs for Vascular Disease Using High Throughput CRISPR Genomics
The NIH/NHLBI has awarded an $11.7M Program Project Grant to Dr, Tom Quertermous and his team of investigators. This program leverages the innovative tools the team has developed to systematically study large numbers of candidate disease genes, define how they integrate into gene programs in vascular cells, test how these programs differ across cell types, vascular beds, disease conditions, and biological sex and thus, identify new genes and pathways that influence risk for vascular diseases.
Dr. Rabinovitch directs Project 3 that focuses on pulmonary arterial hypertension (PAH), a condition attributed to known and unknown genetic factors that is also a complication of many medical conditions including congenital heart disease. Her project aims to identify a shared PAH gene program that is disrupted by many different genetic and environmental factors and that can be targeted to effectively treat PAH. Collaborations with Project 1 focusing on endothelial cells in coronary artery and cerebrovascular disease and with Project 3 focusing on smooth muscle cells in atherosclerosis, will determine differences in gene programs in response to the same perturbation in lung, aortic, coronary and brain endothelial and aortic smooth muscle cells explaining different propensities to PAH and systemic vascular disease. These collaborative studies will be important in informing risk and emerging therapies for different conditions affecting the blood vessel wall.
Postdoctoral Fellow Dr. Mauro Lago-Docampo presented his findings on "Loss of TBX4 Alters Smooth Muscle Contractility and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension" at the TBX4life Conference in San Francisco on March 25–26, 2025. The same abstract was also selected for an oral presentation at Stanford's Heart Center Research Day on March 18, 2025.
In April, Dr. Rabinovitch attended the Amgen 2025 Cardiometabolic Scientific Advisory Board in Chicago.
Dr. Rabinovitch participated in several high-profile events this year. At the 61st Annual Meeting of the Japanese Society of Pediatric Cardiology and Cardiac Surgery in Mie, Japan, she delivered a Special Lecturetitled "The Dawn and the Future Direction of Pediatric Cardiology and Cardiovascular Surgery Research" on Friday, July 11, 2025 at the Mie Center for the Arts. Additionally, she was as Keynote Speaker during the Presidential Symposium on Thursday, July 10, 2025, presenting "Translational Impact of Basic Research in Pulmonary Arterial Hypertension".
She also participated at the 19th International Workshop on Scleroderma Research in Cambridge, UK on July 26–30, 2025, where she presented on “Emerging Therapies in PAH”
2024 Highlights
Dr. Sarasa Isobe is the recipient of the Stanford CVI 2023 Manuscript Award for her manuscript “Reduced FOXF1 Links Unrepaired DNA Damage to Pulmonary Arterial Hypertension” in Nature Communications. Dr. Isobe recently accepted a faculty position at the National Defense Medical College in Japan.
Postdoctoral research fellow, Mauro Lago Docampo, PhD, presented his project “TBX4 Deletion in IPSC Derived Smooth Muscle Cells Causes Impaired Contractility and Apoptosis Resistance, and the Induction of EndMT that in Turn Increases Their Proliferation“ at the Stanford Heart Center Research Day (March 2024), the Department of Pediatrics Research Retreat (June 2024), the Stanford-Arizona-Morehouse-UAB Cardiovascular Research Symposium (August 2024). Dr. Docampo was invited to present his research at the Stanford Pediatrics Pulmonary Division seminar series in October 2024.
Dr. Docampo and Dr. Chongyang Zhang presented posters at the Annual meeting of the American Thoracic Society Annual meeting in San Diego, (May 2024). Dr. Zhang’s presentation was titled ”SOX17 Deficiency is Additive to High Shear Stress in Compromising Endothelial Integrity”.
Dr. Chongyang Zhang and Dr. Mir Adil’s abstracts were selected for moderated digital poster presentations at the American Heart Association’s Scientific Sessions 2024, in Chicago, IL. Dr. Adil discussed “Reduced BMPR2 in Monocytes De-represses HERV-K and Sustains Inflammation in Pulmonary Arterial Hypertension”, and Dr. Zhang, “SOX17 Deficiency is Additive to High Shear Stress in Reducing Endothelial Genes Linked to BMPR2 and NOTCH and Promoting Inflammation in Pulmonary Arterial Hypertension”.
Dr. Rabinovitch presented the lab’s research at national and international meetings this year. At the Pfizer Cardiovascular Symposium, she discussed “Relating Genetics to Pathology of Pulmonary Hypertension to Inform Therapeutic Development” (February 2024); presented the Emory University Pediatric Research Grand Rounds on “Pursuing a Cure for Pulmonary Arterial Hypertension” (March 2024). In April, she spoke on “Linking Genetic Perturbations to Vascular and Myeloid Cell Dysfunction to Find Therapies for Pulmonary Arterial Hypertension” at the University of Pennsylvania. Dr. Rabinovitch was a speaker at the 7th World Symposium On Pulmonary Hypertension in Barcelona, Spain (June 2024), where she was on a Task Force for Pathobiology and mechanisms of disease. Dr. Rabinovitch presented a Special Lecture at Vasculata 2024: Novel insights in Vascular Biology – from Bench to Bedside meeting, hosted by the Stanford Cardiovascular Institute in July 2024, “From integrating pathways to developing novel therapies in pulmonary hypertension“. This Fall, she presented an invited talk on “Single-Cell Imaging Maps Inflammatory Cell Subsets to Pulmonary Hypertension Vasculopathy” at the American Heart Association’s Scientific Sessions 2024, in Chicago, IL.
At Stanford, Dr. Rabinovitch discussed “Linking Genetics to Pathology to Therapy for Pulmonary Arterial Hypertension” at the Stanford CVI’s Frontiers in Cardiovascular Science series (March 2024); and “The Journey to Finding a Cure for Pulmonary Arterial Hypertension“ at the Stanford Heart Center Grand Rounds in August.

