Description:

In this seminar, I will describe how we use an integrative approach to study gene regulation in a variety of cancer types, such as leukemia and bladder cancer. First, I will introduce our recent effort on identifying regulatory variants in childhood acute lymphoblastic leukemia (ALL). Starting from targeted re-sequencing in more than 5,000 patients, we used a combination of high throughput genomics approach and genome editing with CRISPR/Cas9, and identified a non-coding regulatory variant that controls the transcription of oncogenes in ph-like ALL. Second, I will talk about how we identified a bladder cancer subtype-specific master regulator. In this work, we performed ChIP-Seq, ATAC-Seq and RNA-Seq in a panel of bladder cancer cell lines and samples. Knocking down of this novel bladder cancer transcription factor results in global change of gene expression and also affects the cell phenotype, including cell migration and proliferation. In the third project, by performing and analyzing Hi-C experiments, we show that large structural variation (such inter-chromosomal translocation, inversion, and deletions) can induce enhancer-hijacking events in different type of cancers. We developed the first algorithm to date to capture such events genome-wide. To validate the prediction, we deleted the predicted hijacked enhancers, and showed that the expressions of their target genes are significantly reduced. The outcome of this project could shed light on molecular mechanisms of epigenetic regulation in cancer and reveal the key cancer-specific or subtype-specific regulators and pathways, which can be potentially used as cancer biomarkers and therapeutic targets.

Feng Yue, PhD
Associate Professor, Department of Biochemistry and Molecular Genetics,        Director-Center for Cancer Genomics

Northwestern University Feinberg School of Medicine