Biography
- William G Swartchild, Jr. Distinguished Research Professorship, Ann & Robert H. Lurie Children’s Hospital of Chicago
- Director, Genetic Medicine and Nanotechnology Development Center (GeneMeNDer)
- Head, Section for Injury Repair and Regeneration Research, Stanley Manne Children’s Research Institute
- Professor of Pediatrics (Critical Care), Medicine (Pulmonary and Critical Care), and Pharmacology, Northwestern University Feinberg School of Medicine
Youyang Zhao, PhD, is an expert in vascular endothelial cell biology. He serves as Director of the Pediatrics Genetic Medicine and Nanotechnology Development Center (GeneMeNDer) and Head of the Section of Injury Repair and Regeneration Research at Stanley Manne Children’s Research Institute. He is the William G. Swartchild, Jr. Distinguished Research Professor and Professor of Pediatrics, Medicine, and Pharmacology at Northwestern University Feinberg School of Medicine. His translational research is focused on lung and vascular biology to delineate the molecular mechanisms of acute lung injury/acute respiratory distress syndrome, pulmonary hypertension, and cardiovascular diseases, and provide novel therapeutic approaches for these devastating diseases. Dr. Zhao has published many papers in top-tier journals such as Nature Medicine, Proceedings of the National Academy of Sciences of the United States of America, Journal of Clinical Investigation, Journal of Experimental Medicine, Circulation, American Journal of Respiratory and Critical Care Medicine, and Cell Reports. His lab is well-funded with multiple R01 grants. Dr. Zhao is committed to training the next generation of scientists in vascular biology and translational research.
Education and Background
- Postgraduate research molecular biologist, cardiovascular biology, University of California San Diego 2000
- Senior postdoctoral fellow in molecular and cellular biology, Brigham & Women’s Hospital, Harvard Medical School 1998
- Postdoctoral fellow in molecular biology, Harvard University 1996
- PhD, molecular biology, Shanghai Institute of Biochemistry, Chinese Academy of Sciences 1994
- BS, biochemistry, Fudan University 1989
Research Highlights
NOVEL MECHANISM OF ENDOTHELIAL REGENERATION AND RESOLUTION OF INFLAMMATORY LUNG INJURY
Recovery of endothelial barrier integrity after vascular injury is vital for endothelial homeostasis and resolution of inflammation. The objective of this line of research is to identify critical signaling pathways such as p110gammaPI3K/FoxM1 in mediating the intrinsic endothelial regeneration program and determine how aging and epigenetics regulate these processes (J. Clin. Invest. 2006, 116:2333; J. Exp. Med. 2010, 207:1675; Circulation 2016, 133:2447; Sci. Transl. Med. 2023, 15:eabm5755). Dr. Zhao and the research team are also studying the role of endothelial cells in regulating macrophage functional polarization and resolving inflammatory lung injury. These studies will identify druggable targets leading to novel therapeutic strategies to activate the intrinsic endothelial regeneration program to restore endothelial barrier integrity and reverse edema formation for the prevention and treatment of acute respiratory distress syndrome.
NOVEL MECHANISMS OF ENDOTHELIAL INJURY IN THE PATHOGENESIS OF SEPSIS AND ARDS
The purposes of these studies are to define the molecular mechanisms of endothelial pyroptosis in vivo and its role in promoting severe endothelial injury, and to identify the key signaling molecule(s) in mediating severe endothelial injury in aged lungs following sepsis challenge and thus provide novel therapeutic strategies to prevent or inhibit severe injury in sepsis and pneumonia patient and especially in elderly patient population.
NOVEL MECHANISM OF OBLITERATIVE PULMONARY VASCULAR REMODELING
Pulmonary arterial hypertension is a progressive disease with poor prognosis and high mortality. Dr. Zhao and the research team have recently identified the first mouse model of pulmonary arterial hypertension with obliterative vascular remodeling including vascular occlusion and formation of plexiform-like lesions resembling the pathology of clinical pulmonary arterial hypertension (Circulation 2016, 133:2447). Their previous studies also show the critical role of oxidative/nitrative stress in the pathogenesis of pulmonary arterial hypertension as seen in patients (PNAS 2002, 99:11375; J. Clin. Invest. 2009, 119:2009). With these unique models and lung tissue and cells from idiopathic pulmonary arterial hypertension patients, Dr. Zhao and the research team will define the molecular and cellular mechanisms underlying severe vascular remodeling and provide novel therapeutic approaches for this devastating disease.
RNA MODIFICATIONS IN PULMONARY VASCULAR REMODELING AND PULMONARY ARTERIAL HYPERTENSION
The role of RNA base modifications in health and diseases is a hot area of research. RNA N6-methyladenosine (m6A) modification, the most prevalent internal modification of eukaryotic RNA, is an epigenetic modification of adding a methyl group to the N6 site of adenosine, which controls RNA metabolism, including RNA stability, splicing, transport, localization, and translation. The proposed studies employing novel animal models and integrated molecular, cellular, and pharmacological approaches will define for the first time the fundamental role of m6RNA modifications in the regulation of endothelial dysfunction and smooth muscle cell hyperproliferation leading to vasoconstriction and pulmonary vascular remodeling and thus pulmonary arterial hypertension.
ENDOTHELIAL CELL-TARGETED NANOPARTICLE DELIVERY OF DRUGS AND GENES FOR TREATMENT OF VASCULAR DISEASES AND CANCER METASTASIS
The current drug and gene delivery tools such as lipid nanoparticles, adenoviruses, and adeno-associated viruses are mainly accumulated in the liver with little effect on vascular endothelial cells. The overall goal of this line of research is to develop endothelial cell-targeted nanoparticles for delivery of drugs and genes to prevent and treat various diseases caused by endothelial dysfunction. A recent study by Dr. Zhao and the research team has for the first time shown that poly (lactic-co-glycolic acid)-based nanoparticles could target the vascular endothelial cells including the systemic vasculature and pulmonary vasculature to deliver plasmid DNA expressing the genome editing system for robust gene editing in vivo (Cell Reports 2022, 38:110196). The long-term goal of Dr. Zhao and the research team is to develop novel gene therapy approach to target vascular endothelial dysfunction for vascular diseases and cancer metastasis.
Featured Grants
Novel Intrinsic Endothelial Stem Cells Responsible for Lung Endothelial Regeneration and Vascular Repair in ARDS
National Heart, Lung, and Blood Institute
12/22/2023 → 11/30/2027
Novel Roles of RNA Modifications in the Pathogenesis of Pulmonary Vascular Remodeling and PAH
National Heart, Lung, and Blood Institute
09/01/2022 → 06/30/2026
Negative Regulators of Endothelial Regeneration in Aging Lungs and ARDS
National Heart, Lung, and Blood Institute
04/01/2022 → 03/31/2026
Novel Mechanisms of Obliterative Pulmonary Vascular Remodeling and Severe Pulmonary Arterial Hypertension
National Heart, Lung, and Blood Institute
07/01/2016 → 05/31/2025
Novel Mechanisms of Endothelial Injury in the Pathogenesis of ARDS
National Heart, Lung, and Blood Institute
05/01/2020 → 04/30/2025
