Almost all children born with structural heart/lung disease have only one therapy option — surgery. My group works to give these families more options by developing new therapies for early intervention, before the baby is even born. As an instructor in Pediatric Cardiology since 2016, my overarching research goal is to develop a novel therapy to boost the regeneration of the heart, lung and vasculature in patients with a congenital cardiac and/or pulmonary defect.
Our group conducts leading interdisciplinary research using patient-specific induced pluripotent stem cells (iPSCs), derived cardiovascular cells, vessel and lung organoids, animal models, and single cell RNA/ATAC sequencing for disease modeling and high-throughput drug screening. With an established translational research study set-up, we have access to a large patient cohort that provides human tissue for the generation of iPSCs, organoids and single-cell transcriptomic profiling.
We are also interested in exploring the role of vascular insufficiency in causing cardiopulmonary diseases such as congenital heart defects, pulmonary atresia and pulmonary arterial hypertension. We hope to understand the genetic and epigenetic underpinnings of the variation in disease phenotypes and drug response in a personalized manner. Our team works closely with developmental and stem cell biologists, clinicians, bioengineers, translational scientists and entrepreneurs with the common goal of accelerating discovery and facilitating bench-to-bedside translational science.
I decided to pursue research as a medical student, when I realized that there are too many unanswered questions in our field. For example, why do patients have different clinical expressivity? Why do patients respond to drugs differently? Why does part of the heart fail to grow during development? And if the cardiomyocytes stop proliferating soon after birth, can we find a way to reset the clock and help the heart regenerate?
The drive to answer these questions led me to complete my PhD training in stem cells and regenerative medicine, and I have been highly engaged in clinically driven, basic biomedical research since then. I’m also enthusiastic about the possibility of bringing our benchtop discoveries to clinical trials.
My team and I have made several notable discoveries. To understand more about the application of stem cells, we evaluated the therapeutic efficacy of iPSC-derived vascular and cardiac cells using a variety of animal models (mouse, rat, porcine) with cardiomyopathies and vasculopathies. We further elucidated the molecular mechanism using single-cell transcriptomic profiling (Gu et al., Circulation Research, 2012; Gu et al., European Heart Journal, 2015).
To understand patient-specific phenotypes, we utilized iPSC-derived endothelial cells and integrative omics to identify the modifiers that protected unaffected BMPR2 mutation carriers from developing pulmonary arterial hypertension (PAH) (Gu et al., Cell Stem Cell). Using a similar stem cell platform and single cell transcriptomic analysis, we revealed the endocardial and endothelial abnormalities that lead to the valvular and ventricular hypoplasia in single ventricle congenital heart disease.
I’m proud to have received a number of honors and awards during my career. I was a finalist for the 2019 Stanford Cardiovascular Institute Travel Award, and I received the 8th Annual Stanford Art of Science Competition in 2019. I have also been awarded:
In addition to my research, I enjoy teaching and mentoring. My diverse experience includes mentoring high school students, undergraduates, postdoc fellows and clinical fellows for their research in the lab. I also enjoy traveling nationally and internationally to present my work, build up new collaborations and learn about different cultures all over the world.
I am very excited to continue mentoring and advising young scientists. As a woman in science, it is one of my goals to promote diversity in research by reaching out to underrepresented groups and developing opportunities in which they can thrive.
MD: Peking University, Beijing, China, 2009.
PhD: Peking University and Stanford University (joint-training program), 2013.
Fellowship: Stanford University, Stanford, CA, 2016.
Pediatric cardiology; pulmonary arterial hypertension; single ventricle defects
Development of heart, lung, and vasculature; human induced pluripotent stem cells; organoid; high-throughput drug screening; human genetics
Molecular Cardiovascular Biology, Developmental Biology, Neonatology, Perinatal Biology, Pulmonary Biology
KMT2D-NOTCH Mediates Coronary Abnormalities in Hypoplastic Left Heart Syndrome. Circulation Research. 2022; 131:280-282.
iPSC-endothelial cell phenotypic drug screening and in silico analyses identify tyrphostin-AG1296 for pulmonary arterial hypertension. Science Translational Medicine. 2021; 13.
BMP10 Signaling Promotes the Development of Endocardial Cells from Human Pluripotent Stem Cell-Derived Cardiovascular Progenitors. Cell Stem Cell. 2021; 28:96-111.e7.
Capillary cell-type specialization in the alveolus. Nature. 2020; 586:785-789.
Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome. Cell Stem Cell. 2020; 27:574-589.e8.
Endogenous Retrovirus-Derived lncRNA BANCR Promotes Cardiomyocyte Migration in Humans and Non-human Primates. Developmental Cell. 2020; 54:694-709.e9.
Patient-Specific iPSC-Derived Endothelial Cells Uncover Pathways that Protect against Pulmonary Hypertension in BMPR2 Mutation Carriers. Cell Stem Cell. 2017; 20:490-504.e5.
Pravastatin reverses obesity-induced dysfunction of induced pluripotent stem cell-derived endothelial cells via a nitric oxide-dependent mechanism. European Heart Journal. 2015; 36:806-816.
Mingxia Gu, MD, PhD8/17/2020