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Zhiyong Zhao Ph.D.

Academic Title: Assistant Professor
Primary Appointment: Obstetrics, Gynecology and Reproductive Sciences
Secondary Appointments: Biochemistry and Molecular Biology
zzhao@fpi.umaryland.edu
Location: Bressler Research Building, 11-041
Phone: 410-706-8401
Lab: 410-706-5401
 

Personal History:

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.

Research Interests:

Heart development

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.

Diabetic embryopathy

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.

Diagram of diabetic embryopathy

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


Publications:

Zhao Z, Rivkees SA. (2000). Programmed cell death in the developing heart: regulation by BMP4 and FGF2. Dev Dyn 217:388-400. PMID:10767083.

Wei L, Roberts W, Wang L, Yamada M, Zhang S, Zhao Z, Rivkees SA, Schwartz RJ, Imanaka-Yoshida K. (2001). Rho kinases play an obligatory role in vertebrate embryonic organogenesis. Development 128:2953-62. PMID:11532918.

Zhao Z, Rivkees SA. (2003). Rho-associated kinases play an essential role in cardiac morphogenesis and cardiomyocyte proliferation. Dev Dyn 226:24-32. PMID:12508221.

Zhao Z, Rivkees SA. (2004). Rho-associated kinases play a role in endocardial cell differentiation and migration. Dev Biol 275:183-91. PMID:15464581.

Zhao Z, Reece EA. (2005). Nicotine-induced embryonic malformations mediated by apoptosis from increasing intracellular calcium and oxidative stress. Birth Defects Res B Dev Reprod Toxicol 74:383-91. PMID:16193507.

Zhao Z, Reece EA. (2005). Experimental mechanisms of diabetic embryopathy and strategies for developing therapeutic interventions. J Soc Gynecol Investig 12:549-57. PMID:16325743.

Yang P, Zhao Z, Reece EA. (2007). Involvement of c-Jun N-terminal kinases activation in diabetic embryopathy. Biochem Biophys Res Commun 357:749-54. PMID:17449011.

Zhao Z, Wu YK, Reece EA. (2008). Demonstration of the essential role of protein kinase C isoforms in hyperglycemia-induced embryonic malformations. Reprod Sci 15:349-56. PMID:18497343.

Zhao Z, Yang P, Eckert RL, Reece EA. (2009). Caspase-8: a key role in the pathogenesis of diabetic embryopathy. Birth Defects Res B Dev Reprod Toxicol 86:72-7. PMID:19194987. PMCID: 2838243.

Zhao Z (2010). Cardiac malformations and alteration of TGFß signaling system in diabetic embryopathy. Birth Defects Res B Dev Reprod Toxicol 89:97-105. PMID:20127828.

Cao Y, Zhao Z, Eckert RL, Reece EA. (2011). Protein kinase Cß2 inhibition reduces hyperglycemia-induced neural tube defects through suppression of a caspase 8-triggered apoptotic pathway. Am J Obstet Gynecol 204:226 e1-5. PMID:21376163. PMCID: 3057385.

Cao Y, Zhao Z, Eckert RL, Reece EA. (2012). The essential role of protein kinase kinase Cd in diabetes-induced neural tube defects. J Matern Fetal Neonatal Med 25:2020-4. PMID:22463764.

Zhao Z (2012). Endoplasmic reticulum stress in maternal diabetes-induced cardiac malformations during critical cardiogenesis period. Birth Defects Res B Dev Reprod Toxicol 95:1-6. PMID:21922638.

Zhao Z, Eckert RL, Reece EA. (2012). Reduction in embryonic malformations and alleviation of endoplasmic reticulum stress by nitric oxide synthase inhibition in diabetic embryopathy. Reprod Sci 19:823-31. PMID:22534324.

Zhao Z. (2013). Activin-A in diabetes-induced cardiac malformations in embryos. Birth Defects Res B Dev Reprod Toxicol 98:260-7. PMID:23716477.

Zhao Z, Reece EA. (2013). New concepts in diabetic embryopathy. Clin Lab Med 33:207-33. PMID:23702113. PMCID:3685419.

Li X, Zhao Z (2014). MicroRNA biomarkers for early detection of embryonic malformations in pregnancy. J Biomol Res Ther 3. PMID:25859419. PMCID: 4386285.

Zhao Z (2014). TGFß and Wnt in cardiac outflow tract defects in offspring of diabetic pregnancies. Birth Defects Res B Dev Reprod Toxicol 101:364-70. PMID:25231192. PMCID: 4372991.