Faculty & Research

Shao-yu Chen, Ph.D.

Associate Professor
 Department of Cell and Developmental Biology & Bowles Center for Alcohol Studies

Office | 3019 Thurston-Bowles Bldg, CB#7178

Email | syc@med.unc.edu

Lab Website | Fetal Toxicology

Research Interests

My research interests are directed toward achieving a better understanding of the cellular and molecular mechanisms associated with ethanol-induced apoptosis and birth defects.  Specifically, using a combination of state-of-the-art approaches, including proteomics, quantitative real-time PCR and knockout technology, my current research work is focused on the following areas: 1) ROS signaling in ethanol-induced apoptosis and birth defects; 2) Ethanol's interference with L1 cell adhesion molecule; and 3) Proteomic analysis of differential vulnerability to ethanol’s teratogenic effects. The findings from these studies may offer new strategies for development of preventative/ameliorative measures for Fetal Alcohol Spectrum Disorders (FASD).

ROS signaling in ethanol-induced apoptosis and birth defects.

Substantial evidence from our laboratory and others has suggested a major contribution of reactive oxygen species (ROS) to ethanol-induced embryonic cell injury and subsequent teratogenesis. Although many pathways have been suggested to contribute to the ability of ethanol to induce a state of oxidative stress, the major source of ROS in ethanol-exposed embryos remains undefined. We are currently testing the hypothesis that ROS produced by NOX/DUOX family of NADPH oxidases are an important determinant of ethanol-induced apoptosis and teratogenesis. In addition, following up on our studies that have shown the ameliorative potential of exogenous antioxidants, I have initiated a study to determine the role of Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling in the upregulation of endogenous antioxidants in ethanol-exposed embryos.

Ethanol’s interference with L1 cell adhesion molecule

In addition to oxidative stress, alcohol appears to be damaging to a fetus as a result of interference with the L1 cell adhesion molecule (L1). In collaboration with Dr. Michael Charness at Harvard University, we have studied ethanol's interference with L1 cell adhesion molecule, as a probable mechanism underlying alcohol-related birth defects. Our studies have shown that octanol can diminish ethanol-induced apoptosis and ameliorate the adverse developmental effects of ethanol in a whole embryo culture system. This work supports the hypothesis that effects on L1 cell adhesion molecule may contribute to ethanol's teratogenicity. In addition, we have examined the antagonism of ethanol's teratogenesis by NAPVSIPQ (NAP) and SALLRSIPA (SAL), two peptide fragments of the neuroprotective proteins, that can antagonize the inhibition of L1-mediated cell-cell adhesion by ethanol.  The results from this study support the hypothesis that NAP’s antagonism of ethanol’s inhibition of L1 adhesion plays a central role in its prevention of ethanol’s teratogenesis and highlight the potential importance of ethanol’s effects on L1 in the pathophysiology of FASD. We have extended this study to a recently developed maternal oral intake FASD mouse model and found that dietary D-SAL is effective in reducing the incidence of major malformations induced by ethanol exposure.

Proteomic analysis of differential vulnerability to ethanol’s teratogenic effects.

 The purpose of this study is to identify and classify, using proteomics approaches, the protein networks and pathways that mediate critical events in ethanol sensitive versus non-sensitive regions of the developing mouse brain and to reveal proteins that may predispose cells to, or protect them from, ethanol-induced apoptosis. We have found a number of proteins whose expression is altered within hours of ethanol exposure. Changes in protein expression have been observed in both non-sensitive and sensitive cell populations.  Identification of those proteins that are differentially expressed in control and ethanol-exposed mouse brains promises to increase our knowledge of the signaling cascades that mediate ethanol-induced apoptosis and provide insight into the selective vulnerability of certain brain regions.

Center Line Articles

Recent Publications

Click here for a full list of publications from PubMed

Parnell SE, Chen SY, Charness ME, Hodge CW, Dehart DB, Sulik KK. Concurrent Dietary Administration of D-SAL and Ethanol Diminishes Ethanol's Teratogenesis. Alcohol Clin Exp Res. 2007 Oct 19

Parnell SE, Dehart DB, Wills TA, Chen SY, Hodge CW, Besheer J, Waage-Baudet HG, Charness ME, Sulik KK. Maternal oral intake mouse model for fetal alcohol spectrum disorders: ocular defects as a measure of effect. Alcohol Clin Exp Res. 2006 Oct;30(10):1791-8

 Chen SY, Charness ME, Wilkemeyer MF, Sulik KK. Peptide-mediated protection from ethanol-induced neural tube defects. Dev Neurosci. 2005 Jan-Feb;27(1):13-9. 

Chen SY, Dehart DB, Sulik KK. Protection from ethanol-induced limb malformations by the superoxide dismutase/catalase mimetic, EUK-134. FASEB J. 2004 Aug;18(11):1234-6. 

Wilkemeyer MF, Chen SY, Menkari CE, Sulik KK, Charness ME. Ethanol antagonist peptides: structural specificity without stereospecificity. J Pharmacol Exp Ther. 2004 Jun;309(3):1183-9. 

Wilkemeyer MF, Chen SY, Menkari CE, Brenneman DE, Sulik KK, Charness ME. Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8543-8.

Dunty WC Jr, Chen SY, Zucker RM, Dehart DB, Sulik KK.  Selective vulnerability of embryonic cell populations to ethanol-induced apoptosis: implications for alcohol-related birth defects and neurodevelopmental disorder. Alcohol Clin Exp Res. 2001 Oct; 25(10):1523-35.