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Shuli Xia, Ph.D.

Photo of Dr. Shuli Xia, Ph.D.

Research Scientist

Associate Professor of Neurology

Background

Dr. Xia received her doctoral degree in biology from Johannes-Gutenberg University in Mainz, Germany in 1998. She had her post-doctoral training at Washington University School of Medicine in St. Louis, MO and Yale University School of Medicine in New Haven, CT before she came to the Kennedy Krieger Institute in 2002. She became a faculty member at the Kennedy Krieger Institute in 2006.

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Titles

  • Research Scientist
  • Associate Professor of Neurology

Departments / Divisions

Education

Degrees

  • B.S., Sichuan University (China) (1991)
  • Ph.D., Johannes-Gutenberg University - Fak Medicine - Mainz - F R G (407-32 Pr 1/71) (West Germany) (1998)

Research & Publications

Research Summary

My research focuses on understanding the genetic and epigenetic mechanisms of brain tumor malignancy, including tumor proliferation/survival, invasion and the tumor microenvironment. The ultimate goal of my research is to develop novel anti-tumor therapeutic strategies to treat brain malignancy.

(A). Functional analysis of DNA methylation in brain tumor malignancy 

We are interested in the impact of DNA methylation on brain tumor cell gene expression and phenotype changes. We established a new paradigm, by which DNA methylation, a well-accepted repressive epigenetic mark, directs transcription factor binding in a sequence-specific manner. We found that the transcription factor kruppel-like factor 4 (KLF4) interacts with methylated DNA in promoter and enhancer regions to activate gene expression, thereby influencing cellular behaviors including migration, differentiation and mitochondrial function.

Heterozygous mutations in isocitrate dehydrogenase 1 (IDH1) are among the earliest and most common genetic alterations during gliomagenesis. IDH1 mutations generate a neomorphic enzyme activity that converts α-ketoglutarate to D-2-hydroxyglutarate, leading to the inhibition of more than 80 dioxygenases, and consequently global epigenetic alterations including DNA hypermethylation. By employing a highly efficient "single base editing" technique, we established multiple isogeneic cellular models carrying heterozygous IDH1R132/WT. Global genetic and epigenetic analyses reveal that mutant IDH1 modulates interaction between tumor cells and immune cells.

(B). Mechanism of glioma cell migration/invasion

Brain tumor cell migration and infiltration contribute to tumor recurrence. We established an innovative dual-fluorescence approach to study brain tumor migration and invasion in vivo by co-injecting control and experimental cells labeled with different fluorescent dyes. This novel method establishes a rigorous and efficient approach to study tumor invasion regulation in vivo, and at the same time reduced the number of animals needed for invasion studies. Using this method, we investigated the role of EphB2 receptor in glioblastoma proliferation/migration dichotomy. We also determined function of extracellular matrix proteins in brain tumor migration. 

(C). Signaling transduction pathways and glioma cell death 

We are interested in employing various combinatory strategies to selectively induce glioma cell death, including radiation, chemotherapeutic drugs, tyrosine kinase inhibitors, death receptor ligands, histone deacetylase inhibitors and synolytic drugs. In addition, we are interested in targeting glioma stem cells.

Selected Publications

Wei S, Wang J, Oyinlade O, Ma D, Wang S, Kratz L, Lal B, Xu Q, Liu S, Shah S, Zhang H, Li Y, Quinones-Hinojosa A, Zhu H, Huang Z, Cheng L, Qian J, Xia S. Heterozygous IDH1R132H/WT created by "single base editing" inhibits human astroglial cell growth by downregulating YAP. Oncogene, 2018; 37: 5160-5174.

Oyinlade O, Wei S, Kammers K, Liu S, Wang S, Ma D, Huang Z, Qian J, Zhu H, Wan J, Xia S, Analysis of KLF4 regulated genes in cancer cells reveals a role of DNA methylation in promoter-enhancer interactions. Epigenetics, 2018; 13(7):751-768.

Oyinlade O, Wei S, Lal B, Laterra J, Zhu H, Goodwin C, Wang S, Ma D, Wan J, Xia S. Targeting UDP-α-D-glucose 6-dehydrogenase inhibits glioblastoma growth and migration. Oncogene, 2018, 37(20):2615-2629.

Wan J, Su Y, Song Q, Tung B, Oyinlade O, Liu S, Ying M, Ming GL, Song H, Qian J, Zhu H and Xia S. Methylated cis-regulatory elements mediate KLF4-dependent gene transactivation and cell migration. eLife. 2017; 6. pii: e20068.

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