About

Ziqiao Wang is an Assistant Professor in the Department of Genome Sciences at the University of Virginia School of Medicine. He holds a PhD in Biostatistics from The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences and completed postdoctoral training in Biostatistics at Johns Hopkins University. His research focuses on how genetics, genomics, and environmental factors together drive the development of human diseases. He specializes in statistical methodology developments, data analysis, and theoretical investigations, utilizing large-scale datasets from biobanks and epidemiological studies that include molecular genetic and genomic data, along with human behavioral and lifestyle factors. His work includes developing novel statistical methods to jointly model gene-environment correlations and interactions using polygenic scores in case-control studies, with applications in datasets such as the UK Biobank. He has also developed methods for estimating risk parameters of polygenic scores in family-based studies to understand genetic direct, indirect, and gene-environment interactions, with applications in autism research through the SPARK Consortium. Additionally, Wang investigates integrative omics using individual-level and summary statistics to understand disease mechanisms and improve disease risk predictions, employing machine learning algorithms to enhance the statistical power of large-scale association studies. His research extends to identifying DNA methylation biomarkers associated with pancreatic cancer and discovering potential pre-diagnostic plasma proteomic markers for multiple solid cancers within prospective cohort studies.

Research topics

• Biology
• Genetics
• Cell biology
• Computational biology
• Chemistry
• Cancer research
• Molecular biology

Selected publications

• UTX condensation underlies its tumour-suppressive activity

  Nature · 2021 · 198 citations

  • Cell biology
  • Chemistry
  • Biology
  DOI

• Cancer-specific CTCF binding facilitates oncogenic transcriptional dysregulation

  Genome biology · 2020 · 125 citations

  • Biology
  • Genetics
  • Computational biology

  BACKGROUND: The three-dimensional genome organization is critical for gene regulation and can malfunction in diseases like cancer. As a key regulator of genome organization, CCCTC-binding factor (CTCF) has been characterized as a DNA-binding protein with important functions in maintaining the topological structure of chromatin and inducing DNA looping. Among the prolific binding sites in the genome, several events with altered CTCF occupancy have been reported as associated with effects in physiology or disease. However, hitherto there is no comprehensive survey of genome-wide CTCF binding patterns across different human cancers. RESULTS: To dissect functions of CTCF binding, we systematically analyze over 700 CTCF ChIP-seq profiles across human tissues and cancers and identify cancer-specific CTCF binding patterns in six cancer types. We show that cancer-specific lost and gained CTCF binding events are associated with altered chromatin interactions, partially with DNA methylation changes, and rarely with sequence mutations. While lost bindings primarily occur near gene promoters, most gained CTCF binding events exhibit enhancer activities and are induced by oncogenic transcription factors. We validate these findings in T cell acute lymphoblastic leukemia cell lines and patient samples and show that oncogenic NOTCH1 induces specific CTCF binding and they cooperatively activate expression of target genes, indicating transcriptional condensation phenomena. CONCLUSIONS: Specific CTCF binding events occur in human cancers. Cancer-specific CTCF binding can be induced by other transcription factors to regulate oncogenic gene expression. Our results substantiate CTCF binding alteration as a functional epigenomic signature of cancer.

  DOI

• Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements

  iScience · 2020 · 27 citations

  • Biology
  • Cell biology
  • Molecular biology

  . Here we report that polyadenylation of H3.1 mRNA increases H3.1 protein, resulting in displacement of histone variant H3.3 at active promoters, enhancers, and insulator regions, leading to transcriptional deregulation, G2/M cell-cycle arrest, chromosome aneuploidy, and aberrations. In support of these observations, knocking down the expression of H3.3 induced cell transformation, whereas ectopic expression of H3.3 attenuated arsenic-induced cell transformation. Notably, arsenic exposure also resulted in displacement of H3.3 from active promoters, enhancers, and insulator regions. These data suggest that H3.3 displacement might be central to carcinogenesis caused by polyadenylation of H3.1 mRNA upon arsenic exposure. Our findings illustrate the importance of proper histone stoichiometry in maintaining genome integrity.

  DOI

Frequent coauthors

• Chongzhi Zang

  University of Virginia

  66 shared

• Zhangli Su

  University of Alabama at Birmingham

  17 shared

• Yoshiyuki Shibata

  Kure Medical Center

  17 shared

• Etsuko Shibata

  University of Alabama at Birmingham

  17 shared

• Anindya Dutta

  University of Alabama at Birmingham

  16 shared

• Richard D. Minshall

  University of Illinois Urbana-Champaign

  14 shared

• Chinnaswamy Tiruppathì

  University of Illinois Chicago

  14 shared

• Asrar B. Malik

  University of Illinois Chicago

  14 shared

Education

• PhD, Quantitative Sciences-Biostatistics

  The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

  2021

• BS, Mathematics and Statistics

  Stony Brook University

  2015

• BS, Mathematics

  Nanjing University

  2013

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