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Cheng Xu, PhD

Academic Title:

Research Associate

Primary Appointment:

Obstetrics, Gynecology and Reproductive Sciences

Location:

655 West Baltimore Street

Phone (Primary):

410-706-1214

Fax:

410-706-5747

Education and Training

1987-1991 BS., Marine Biology, Qingdao University of Oceanography (Now: Ocean University of China), P. R. China

1993-1996 MS., Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, P. R. China

1997-2000 DSc., Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, P. R. China

Biosketch

I have joined Dr. Peixin Yang Lab in 2010. In this lab, my research is focusing on the mechanism underlying maternal diabetes-induced neural tube defects (NTDs). Globally there are more than 300,000 NTD-affected pregnancies each year, and NTDs cause significant infant mortality and childhood morbidity. Our research has revealed cellular organelle stress, including ER stress, impaired autophagy and Mitochondrial dysfunction, as important cause of diabetic embryopathy.

 

We found maternal diabetes suppressed autophagy and delayed neurogenesis by blocking neural progenitor differentiation. I found treatment with trehalose, an autophagy inducer, reversed autophagy impairment and prevented NTDs in diabetic pregnancies. Trehalose resolved homeostatic imbalance by correcting mitochondrial defects, dysfunctional proteins, ER stress, apoptosis, and delayed neurogenesis in the neural tubes exposed to hyperglycemia. This finding provides evidence for the potential efficacy of trehalose as an intervention against hyperglycemia-induced NTDs.

 

I also revealed a function for PGC-1α in embryonic development through promoting autophagy and ameliorating hyperglycaemia-induced NTDs. We demonstrated that PKCα increases the expression of miR-129-2, which is a negative regulator of autophagy. miR-129-2 represses autophagy by directly targeting PGC-1α, a positive regulator for mitochondrial function, which is disturbed by maternal diabetes. Deleting Prkca, or overexpressing PGC-1α, reverses diabetes-induced cellular stress, leading to a NTD reduction. In addition to function of PGC-1α, these findings identified two negative autophagy regulators, PKCα and miR-129-2, which mediate the teratogenicity of hyperglycaemia leading to NTDs.

 

Senescence is a recently recognized developmental program, which is essential for embryonic development. We found premature senescence induced by maternal diabetes in the developing neuroepithelium leading to NTDs. I characterized the key features of premature senescence in diabetic embryopathy, uncovered a FoxO3a and miR-200c-mediated premature senescence pathway.  Our results provided the mechanistic basis for targeting the new developmental program for intervention against maternal diabetes-induced NTDs.

 

In recent years it has become apparent that Epigenetic mechanisms are involved in the regulation and expression of genes. Dr. Yang’s group is the very first one to reveal DNA hypermethylation and histone hyperacetylation as the cause of gene dysregulation in diabetic embryopathy. DNA methylation occurs at cytosines and is generally associated with transcriptional silencing. My research showed that DNA hypermethylation induced by maternal diabetes suppressed gene expression levels and disturbed sub-cellular distribution patterns of core components of planar cell polarity (PCP) signaling pathway. Since the tissue convergence and extension (CE), which drive cell rearrangement during epithelial morphogenesis in mammalian embryos, are dependent on PCP signaling, dysregulation of PCP core genes by hypermethylation leads to NTDs. Currently, I’m employing CRISPR/CAS9 genome editing as well as other cutting edge technologies to generate conditional knock out mouse line to research the molecular foundation of diabetic embryopathy. I believe my work on epigenetics will contribute to understanding of the mechanisms underlying diabetic embryopathy, and help to elucidate hidden causes of this disease.

Research/Clinical Keywords

Diabetic embryopathy, neural tube defects

Highlighted Publications

 

C Xu, X Chen, EA Reece, W Lu, P Yang, 2019. The increased activity of a transcription factor inhibits autophagy in diabetic embryopathy. Am J Obstet Gynecol. 220(1):108.e1-e12.

P Yang, C Xu, EA Reece, X Chen, J Zhong, M Zhan, DJ Stumpo, PJ Blackshear, P Yang, 2019. Tip60- and sirtuin 2-regulated MARCKS acetylation and phosphorylation are required for diabetic embryopathy. Nat Commun. 10(1):282.

 

F Wang1, C Xu1, Y Wu, EA Reece, X Li, C Harman, J Yu, D Dong, C Wang, P Yang, J Zhong, P Yang, 2017.  Protein kinase C-alpha suppresses autophagy and induces neural tube defects via miR-129-2 in diabetic pregnancy. Nat Commun.  8: 15182

1These authors contributed equally to this article.

C Xu, X Li, F Wang, H Weng and P Yang 2013 Trehalose prevents neural tube defects by correcting maternal diabetes-suppressed autophagy and neurogenesis. Am J Physiol Endocrinol Metab 305: 667-678

 

Lab Techniques and Equipment

Genetics

  • Knockout mice and conditional knockout mice
  • Transgenic mice via molecular recombineering
  • Transgenic fish via microinjection and electroporation

Molecular Biology

  • Microarray sample preparation, hybridization and data analysis
  • DNA, RNA isolation, purification, quantification and cloning
  • Protein isolation and purification
  • Southern, Northern and Western blotting analysis
  • Co-immunoprecipitation and chromatin immunoprecipitation (ChIP)
  • Gel electrophoresis, including starch gel, PAGE, SDS-PAGE, IEF-PAGE
  • Standard PCR, long-distance PCR, RT-PCR and quantitative PCR

Histology and Microscopy

  • Paraffin, vibratome and cryostat sectioning and staining
  • Immunofluorescent labeling and in situ hybridization with whole mount embryos and sections, double color and in situ plus  immuno fluorescent staining
  • Micro-photography with confocal and compound microscope

 Cell Culture

  • Bacterial, yeast, mammalian cell and mouse stem cell
  • Primary cell culture of fish and mouse