Dr. Zhiyong Zhao earned a PhD degree in Developmental Biology from the University of Manchester, England, and completed his postdoctoral training at Pennsylvania State University and Yale University School of Medicine. Prior to joining the faculty of the University of Maryland School of Medicine in 2006, he served as an associate research scientist in the Department of Pediatrics at Yale University School of Medicine from 2000 to 2004 and assistant professor (tenure track) in Department of Obstetrics and Gynecology at the University of Arkansas for Medical Sciences from 2004 to 2006. He is also a faculty member of the Graduate School at University of Maryland Baltimore.
Dr. Zhao served on study sections and special review panels of the National Institutes of Health, special emphasis panel of the Centers for Disease Control and Prevention, review panel of Israel Science Foundation, and review panel of Czech Science Foundation. He currently serves as an editorial board member for Journal of Biomolecular Research and Therapeutics and Journal of Biochemistry & Molecular Biology.
Cardiogenesis is controlled by complex molecular interactions. Anomalies in the heart, such as hypoplastic heart and ventricular septal defects, are associated with decreased proliferation and migration of cardiomyocytes and endocardial cells. Dr. Zhao's research focuses on intracellular signaling involving Rho GTPase and Rho-associated coiled-coil kinases (ROCKs) in regulation of genes that control these cellular activities.
Hyperglycemia during early pregnancy can cause developmental malformations in the embryo resulting in birth defects, a diabetic complication known as diabetic embryopathy. The most common congenital anomalies occur in the central nervous and cardiovascular systems, known as neural tube defects (Fig. 1) and heart defects (Fig. 2). Formation of these abnormalities is associated with increased programmed cell death, decreased cell proliferation, and suppressed cell migration in embryonic structures.
High glucose disturbs intracellular metabolic homeostasis and organelle functions in the endoplasmic reticulum (ER) and mitochondria, generating intracellular stress conditions such as ER stress and oxidative stress. One of the Dr. Zhao's research foci is to identify signaling molecules generated by phospholipid metabolism which trigger cell signaling events leading to embryonic malformations. Dr. Zhao's research also aims to address the actions of ER stress-activated molecular cascades, including transcription factor C/EBP homologous protein (CHOP)-controlled gene expression and eukaryotic translation initiation factor 2a kinase 3 (eIF2aK3)-eIF2a-regulated protein translation, leading to aberrant cellular activities and, consequently, developmental malformations.
Birth defects associated with tobacco-smoking
Chemicals in tobacco smoke perturb the development of the embryo in pregnancy. Among them, nicotine causes cell death and structural malformations in the embryo by increasing levels of intracellular calcium and reactive oxygen species (oxidative stress). Dr. Zhao's research aims to address the mechanisms by which nicotine induces calcium elevation and calcium-induced molecular cascades, leading to increased programmed cell death and embryonic abnormalities.
Interventions to prevent birth defects
The ultimate goal of Dr. Zhao's research is to develop interventions to prevent birth defects. High glucose, nicotine and other environmental teratogens disturb metabolic homeostasis in the embryo, generating intracellular stress. Dr. Zhao's group explores potential interventional strategies to target nitrosative stress, using nitric oxide synthase inhibitors; alleviate ER stress, using chemical chaperones; and ameliorate oxidative stress, using antioxidants; to protect the embryos from teratogenic insults.
Lab Techniques and Equipment:
Dr. Zhao's group utilizes several in vivo and in vitro model systems, including streptozotocin-induced diabetic mouse models, whole embryo culture, organ culture, epithelial-mesenchymal transformation assay, cell migration assay, and in situ hybridization.
Grants and Contracts:
NIH R01HD076245: 7/16/2013-4/30/2018
NIH R03HD075995: 7/14/2014-6/30/2016