Thoracic Surgery & Upper Gastrointestinal
Cancer Research Laboratories

Postdoctoral Fellow - Dr. Swneke Bailey lab

research Project

My projects focus on the investigation of extensive epigenetic reprogramming that accompanies the progression of cancers to metastasis. My first project aims to identify epigenetic changes promoting the progression of Gastro-esophageal adenocarcinoma (GEA) to peritoneal metastasis (PM) by profiling multiple matched patient trios (normal, primary tumour, and peritoneal metastasis from the same patient) for H3K27Ac and H3K27me3.

My second project aims to identify transcription factors (TFs) altering the epigenetic and transcriptional landscape of GEA that promote PM. Using publicly available data, we discovered that the motif of certain TFs are enriched within the identified gained regulatory elements. Interestingly, these factors are active in our profiled PM sample. Our goal is to apply this approach to our patient trios to identify additional TFs driving PM. In order to better extract TF binding motifs from large regions marked by histones, we developed a computational tool called HisTrader, which allows more accurate data-mining of histone ChIP-seq data and extract the corresponding DNA sequences for motif enrichment analyses. The validation of HisTrader is close to completion and it is already published on BioRxiv. We also aim to characterize the role of the identified disrupted genes and TFs promoting peritoneal metastasis. We will deploy lentiviral overexpression and shRNA knockdown experiments in gastric cell lines, as well as in xenograft mouse models.

Through these projects, we will assess the role of our candidate genes in the progression of gastric cancer to PM and determine whether they represent a new potential actionable targets or biomarkers for precision medicine of GEA. Moreover, intended as the first clinically useful epigenomic mapping of PM-specific genes in GEA, it could also provide a methodology that is applicable to other types of cancer.

Research interests

• Identification of epigenetic driver events of metastasis in gastric cancer.
• Role of non-coding RNA in dysregulation of gene expression
• Application of data science in prognosis and treatment prediction using epigenetic landscape of patient samples
• Development of clinical biomarkers using the above approaches

Yifei Yan