In March, Dr. Mingxia Gu, Instructor, received the Best Oral Abstract Award at the First Annual Heart Center Research Day for the Betty Irene Moore Children's Heart Center at Lucile Packard Children's Hospital. Her abstract was entitled: High-Throughput Drug Screening of iPSC-Derived Vascular Cells to Reverse Pulmonary Arterial Hypertension Phenotype. (Dr. Gu - left, pictured with Dr. Sharon Paige)
Dr. Rabinovitch served as co-Chair of the Task Force on “Pathology and Pathobiology” at the 6th World Symposium on Pulmonary Hypertension in Nice, France (February 27 – March 1, 2018). This symposium series was started in 1973, and is held every 5 years to mark the progress in pulmonary hypertension science and anticipate future developments. The published conference proceedings constitute a collection of articles among the most cited in this scientific area.
Dr. Rabinovitch is the 2017 AHA Distinguished Scientist Lecturer......
Dr. Rabinovitch was named as the American Heart Association (AHA) Distinguished Scientist Lecturer for the Annual AHA Meeting in Anaheim this year. The AHA Distinguished Scientists are a prominent group of scientists and clinicians whose work has importantly advanced our understanding of cardiovascular diseases and stroke. This award was created over 10 years ago to recognize AHA/ASA members for significant, original and sustained scientific contributions that have advanced the association's mission. “This is a signal acknowledgment, made even more remarkable by her winning the Amberson Lectureship at the ATS last year. These awards reflect the high regard towards Marlene held by academic physicians and physician-scientists.” Said Dr. Mark Nicolls, Professor and Chair of Stanford Pulmonary and Critical Care Medicine and a long-time collaborator. Dr. Rabinovitch was recognized at the Annual AHA Scientific Sessions Opening Session, on November 12, 2017. Her lecture was titled “Genetic and Epigenetic Determinants of the Inflamed Vessel Wall Inform New Treatments for Pulmonary Hypertension and Other Vascular Diseases”.
Also at the 2017 AHA Scientific Session, Dr. Rabinovitch participated in an ATVB Journal Club Session on iPSC derived cell types relevant to atherosclerosis, where she talked about “iPSC-Derived Endothelial Cells”, and presented a talk titled “Patient specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect Against Pulmonary Hypertension in BMPR2 Mutation Carriers” in a session addressing the use of iPSCs to delineate mechanisms of abnormal cardiac development and disease.
Our lab was well-represented at the meeting. Recent lab alum Jan K Hennigs, MD, was selected as a 2017 Cournand and Comroe Young Investigator Award Finalist. He presented a paper on his post-doctoral research project, “Inducible PPARγ-p53 Transcription Factor Complex Preserves Pulmonary Endothelial Homeostasis and Promotes Vascular Regeneration to Reverse Pulmonary Hypertension”.
Mingxia Gu, MD, PhD, talked about “High-Throughput Drug Screening of iPSC-Derived Vascular Cells to Reverse PAH Phenotype”. Dr. Gu received a Travel Award from the Stanford Cardiovascular Institute to attend the meeting. Dan Li. PhD, presented a poster on “ALDH1A3 Regulates Chromatin Remodeling and Smooth Muscle Cell Proliferative Genes in PAH” and Shalina Taylor, PhD on “Neutrophils in Pulmonary Arterial Hypertension Show Heightened Elastase, Propensity to Form Extracellular Traps and an Antiviral Signature”
Other Highlights in 2017:
Three of our post doctoral fellows received competitive post-doctoral awards. Mingxia Gu, MD, PhD, received an NIH Pathway to Independence Award (K99/R00) to carry out research on “Uncovering compensatory mechanisms in family members with disease causing mutations of pulmonary hypertension”. Dr. Gu also received the Stanford Cardiovascular Institute Best Manuscript Award for her paper published in Cell Stem Cell, “Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers” (M Gu et al, Cell Stem Cell 2017; 20:490-504). Dan Li, PhD, was awarded a Senior Research Training Fellowship from the American Lung Association for her research on “The Role of ALDH1A3 in Regulating the Hyperpoliferative Phenotype of Smooth Muscle Cells in PAH”, and Shalina Taylor, PhD was awarded a slot on the NIH/NHLBI Stanford Training Program in Lung Biology, T32 HL129970.
Our lab research was presented nationally and internationally this year. Dr. Rabinovitch talked on “Reduced BMPR2 Promotes Endothelial-to-Mesenchymal Transition via HMGA1 and Its Target Slug” at the 11th PVRI Annual World Congress in Miami, FL. She was a Keynote Lecturer at the 81st Annual Scientific Meeting of the Japanese Circulation Society in Kanazawa, Japan, where she talked on “Smooth Muscle Primes Endothelium for Regeneration by Coordinating Metabolism, Chromatin Remodeling and Gene Expression: Implications for Systemic Vascular Disease and Pulmonary Arterial Hypertension”. Studies on the intersection of inflammation and genetics in pulmonary hypertension were featured at the R.L. Johnson Visiting Professorship at the University of Texas Southwestern, and in Scotland, at the Cardiovascular Symposium at the University of Glasgow Institute of Cardiovascular and Medical Sciences. Dr. Rabinovitch discussed “A BMP-Notch Axis Coordinates Mitochondrial Function, Chromatin Remodeling and Gene Regulation to Regenerate Endothelium in Response to Injury” at the Angiogenesis and Vascular Disease Keystone Symposium in Santa Fe, New Mexico, and participated in the American Thoracic Society (ATS) International Meeting Symposium on “Hemodynamic Stress is NOT the Most Important Driver in the Pathogenesis of Occlusive Neointimal Lesions in PAH” in Washington DC.
Dr. Rabinovitch is a co-organizer of the NAVBO Vascular Biology 2017 Vascular Matrix Biology and Bioengineering Workshop in Monterey, CA, in October 2017. This workshop is designed to promote exchange of ideas between vascular matrix biologists, cardiovascular regenerative medicine, and cardiovascular engineers. It featured talks on vascular tissue engineering, mechanotransduction, vascular mechanics, the extracellular matrix and disease, vascular calcification, vascular imaging and engineering angiogenesis. Mingxia Gu, MD, PhD travelled to Shimane, Japan, to attend The 8th TAKAO International Symposium on Molecular Mechanism of Cardiopulmonary Disease in October 2017. She spoke on “Using Patient-Specific iPSCs to Understand and Treat Pulmonary Arterial Hypertension”.
In addition to the Robert F. Grover Prize from the Assembly on Pulmonary Circulation, Dr. Rabinovitch received what is considered to be the highest honor accorded by the ATS, the J. Burns Amberson Lecture at the American Thoracic Society’s annual meeting in San Francisco on May 15, 2016. The lecture honors the late Dr. Amberson, an international authority on chest disease and tuberculosis, and recognizes “a career of major lifetime contributions to clinical or basic pulmonary research and/or clinical practice.”
Dr. Rabinovitch was the 32nd Annual Laurence H. Green Memorial Lecturer at the Medical Grand Rounds at the Peter Bent Brigham Hospital, Harvard Medical School, Boston
The lecture addressed Crossing the Intersection Between Genetics and Inflammation to Find New Treatments for Pulmonary Arterial Hypertension. During this visit, Dr. Rabinovitch was also invited to present the Cardiovascular Ground Rounds discussing Novel Functions of PPARgamma in the Vascular Response to Injury.
Dr. Rabinovitch presented work from the laboratory at many high profile National and international meetings and conferences. Her lectures introduced novel approaches to therapy for pulmonary hypertension and other cardiovascular disorders based upon basic research from the laboratory.
The themes of the lectures were related to the intersection of inflammation and genetics in the pathobiology of pulmonary hypertension. She spoke at the Joint Symposium of the Excellence Cluster Cardio-Pulmonary System (ECCPS), the 2014 International Conference of the American Thoracic Society (ATS) in San Diego, the Pulmonary Vascular Research Institute (PVRI) in Bad Nauheim, Germany, and the 7th International Neonatal and Childhood Pulmonary Vascular Disease Conference in San Francisco. Additionally, Dr. Rabinovitch gave a State of the Art Review at the NIH 1st Annual Drug Discovery and Development Symposium for Pulmonary Hypertension in Bethesda, MD, and gave Research Rounds at NYU’s Langone Medical Center, the University of California, San Diego, the University of Wisconsin-Madison, and at the CVI seminar series of Boston University. At Stanford, Dr. Rabinovitch received the 2015 Department of Pediatrics Mentor Award of Excellence.
The Journey from the Bench to the Bedside
Dr. Rabinovitch and a team from Stanford and Proteo were invited by the FDA to discuss the development plan for Elafin (Tiprelestat) injection for the treatment of pulmonary arterial hypertension. Elafin, an elastase inhibitor, is being developed by Proteo (http://proteo.us/) in collaboration with Marlene Rabinovitch, M.D., at Stanford University. Elafin received Orphan Drug Designation for treatment of PAH by the FDA and in Europe. The team is preparing a Pre-Investigational New Drug Application (PIND) in 2016.
Our Post Doctoral Fellows Presentations
The lab was once more well represented at the two key conferences of the cardiovascular field. Three of our fellows presented their research as posters at the 2015 International Conference of the American Thoracic Society (ATS) in Denver, CO, in May. Pin-I Chen, PhD, presented “Amphetamine Enhances the Propensity of Pulmonary Arterial Endothelial Cells to Apoptosis and DNA Damage via pAkt-Dependent Pathways” (P-I Chen, A Cao, NF Tojais, CG Li, L Wang, M Rabinovitch); Jan K Hennigs, MD, presented “The Transcriptional PPARÎ³-p53 Complex Represses Osteoprotegerin Expression Upon DNA Damage to Inhibit Pulmonary Arterial Smooth Muscle Cell Proliferation” (Jan K. Hennigs, Matthew Roughley, Pin-I Chen, C. Grace Li and Marlene Rabinovitch); and Nancy F Tojais, PhD, presented “Pulmonary arterial hypertension patients with BMPR2 mutation show impaired vascular elastin fiber assembly” (NF Tojais, A Cao, P-I Chen, RK Hopper, CJ Rhodes, L Wang, M Rabinovitch). In November, at the 2015 American Heart Association (AHA) Scientific Sessions in Orlando, FL, post doctoral fellow Kazuya Miyagawa, MD, PhD presented a poster on “Contact-Mediated Interaction between Pulmonary Artery Endothelial and Smooth Muscle Cells Promotes a BMPR2-Î²-catenin-Notch1 Signal Causing Hyperpolarization of Endothelial Mitochondria and a Stalk Cell-Like Phenotype” (K Miyagawa, CG. Li, JK. Hennigs, S Taylor, JR Moonen, S Sa, L Wang, A Cao, M Rabinovitch).
Lab members also presented their results on work with induced Pluripotent stem cells at the International Society for Stem Cell Research in Stockholm, Sweden, in June 2015. Postdoctoral fellow Mingxia Gu, MD, PhD, presented her work on “Patient-specific IPSC Derived Endothelial Cells Uncover Mechanisms Related to Penetrance of a BMPR2 Mutation in Causing Pulmonary Arterial Hypertension” (M Gu, S Sa, Y Ma, JC Wu, M Rabinovitch) and a poster reported the work of Research Associate Silin Sa, PhD, on “Induced Pluripotent Stem Cell Derived Endothelial Cells as Surrogates for Drug Screening in Idiopathic Pulmonary Arterial Hypertension” (S Sa, A Cao, M Gu, Y Ma, R Fong, CG Li, L Nguyen, JC Wu, M Rabinovitch). In January 2016, postdoctoral fellow Caiyun (Grace) Li, PhD, will present a poster on “PPARgamma controls the DNA damage response by modulating UBR5 interaction with the MRE11-RAD50-NBS1 complex” (CG Li, CS Mahon, E Verschueren, V Kantamani, K Cimprich and M Rabinovitch) at the Keystone Symposium on Nuclear Receptors: Full Throttle in Snowbird, UT.