Yafeng Dong, Ph.D.

Associate Professor
Director, Molecular Biology Core Facility
Department of Obstetrics and Gynecology
Member, Center for the Developmental Origins of Health and Adult Disease

Ph.D., Xian Medical University, China, 1999
Postdoctoral, University of Maryland, 2000-2006


ydong@kumc.edu

The problem of perinatal brain injury, in terms of the costs to society and to the affected individuals and their families, is extraordinary. The most common underlying cause of perinatal brain injury is hypoxia/ischemia.  Intrauterine hypoxia and birth asphyxia induced brain damage are associated with increased perinatal mortality and long term sequelae of neurodevelopmental compromise, seizure disorders and cerebral palsy.  The roles of ROS, Ca2+, NMDA receptors, excitatory amino acids, and apoptotic genes on fetal brain injury have been studied exclusively. These works have led to substantial conceptual agreement on a general outline of how fetal brain injury triggers and evolves to produce neuropathologic lesions and neurodevelopmental disabilities. However, the precise etiological factors responsible for the development of the majority of fetal hypoxic brain injury have not been identified.

Role of proinflammatory cytokines in fetal brain injury during chronic hypoxia

Our studies reveal an association between fetal hypoxemia damage and a marked inflammatory reaction that contributes to the tissue injury.  With the approach of gene microarray and quantitative PCR techniques, we demonstrated that hypoxia induced stress created fetal organ damage via up regulation fetal pro-inflammatory cytokines. Pro-inflammatory cytokines play a central role in the causation of fetal organ damage in the hypoxia condition. The ultimate goal of our lab is to study the molecular mechanism of pro-inflammatory cytokine regulation in hypoxemia fetus.

Proteomic identification of specific proteins induced by chronic hypoxia in fetal organ damage

By utilizing advanced proteomic techniques, we found phosphorylated cofilin-1 to be dramatically down regulated in hypoxic fetal brain. We hypothesize that chronic hypoxia induces the cofilin post-translational modifications, which are mediated by ROS. Dephosphorylated cofilin may evoke activation of apoptotic genes leading to neuronal damage in the preterm hypoxic fetal brain. Further studies will be performed, we hope the findings may provide a new concept resulting in the development of a pharmacological inhibitor to inactivate cofilin and prevent chronic hypoxia, which would have a major impact on the treatment of brain injuries in the fetus.

Selected Publications

Oh C, Dong Y, Liu H, Thompson LP. Intrauterine hypoxia upregulates proinflammatory cytokines and matrix metalloproteinases in fetal guinea pig hearts. Am J Obstet Gynecol. 2008 Jul;199(1):78.e1-6.

Oh C, Dong Y, Harman C, Mighty HE, Kopelman J, Thompson LP. Chronic hypoxia differentially increases glutathione content and gamma-glutamyl cysteine synthetase expression in fetal guinea pig organs. Early Hum Dev. 2008 Feb;84(2):121-7.

Yurovsky VV, Gerzanich V, Ivanova S, Dong Y, Tsymbalyuk O, Simard JM. Autocrine TGF-beta1 mediates angiotensin II-induced proliferative response of cerebral vessels in vivo. Am J Hypertens. 2007 Sep;20(9):950-6.

Dong Y, Thompson LP. Differential expression of endothelial nitric oxide synthase in coronary and cardiac tissue in hypoxic fetal guinea pig hearts. J Soc Gynecol Investig. 2006 Oct;13(7):483-90.

Dong Y, Gao D, Chen L, Lin R, Conte JV, Wei, C. Increased ERK activation and decreased MKP-1 expression in human myocardium with congestive heart failure. J Cardiothoracic-Renal Res. 2006; 1(2):123-130.

Thompson LP, Dong Y. Chronic hypoxia decreases endothelial nitric oxide synthase protein expression in fetal guinea pig hearts. J Soc Gynecol Investig. 2005 Sep;12(6):388-95.

Lin R, Roseborough G, Dong Y, Williams GM, Wei C. DNA damage and repair system in spinal cord ischemia. J Vasc Surg. 2003 Apr;37(4):847-58.

Dalton S, Gerzanich V, Chen M, Dong Y, Shuba Y, Simard JM. Chlorotoxin-sensitive Ca2+-activated Cl- channel in type R2 reactive astrocytes from adult rat brain. Glia. 2003 Jun;42(4):325-39.

Last modified: Jul 16, 2014

Yafeng Dong, Ph.D.

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Yafeng Dong, Ph.D.
Associate Professor
Director, Molecular Biology Core Facility
Department of Obstetrics and Gynecology

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