Research in the Tan Laboratory encompasses four areas: transcriptional regulation of embryonic hematopoiesis and T-cell differentiation; the role of three-dimensional chromosome organization in hematopoiesis and pediatric cancer; the role of noncoding sequence variants in pediatric cancers; and single-cell analysis of embryonic hematopoiesis and tumor microenvironment.
The ontogeny of hematopoietic stem cells (HSCs) and T-cell differentiation are driven by a series of gene expression programs over time. The Tan Lab is developing cutting-edge genomic and computational tools to profile and model the gene regulatory circuitry in these two developmental systems. The team's studies have revealed a repertoire of highly dynamic transcriptional regulatory sequences as well as transcriptional regulators that are previously uncharacterized. Additional studies are underway to experimentally test novel regulatory DNA sequences and transcriptional regulators.
In addition, the lab has developed computational methods for identifying large-scale and hierarchically organized chromosome domains and long-distance enhancer-promoter interactions. In ongoing work, the Tan Lab is combining experimental assays and computational methods to study the role of 3D genome re-organization in HSC maturation and leukemogenesis.
The lab has developed a general computational framework for identifying noncoding mutations that confer disease risk. It has then applied the method to nominate candidate causal noncoding mutations in five major pediatric cancers. In ongoing work, the lab is experimentally testing several recurrent structural variants predicted to disrupt enhancer activities in B-cell acute lymphoblastic leukemia.
In ongoing projects, the Tan Lab is using single-cell RNA-Seq to identify novel precursor cell populations of embryonic HSCs. Additionally, as a member of the NCI-funded Human Tumor Atlas Network, the lab has established the Center for Pediatric Tumor Cell Atlas to better understand clonal evolution and tumor heterogeneity at the single-cell level for three types of high-risk pediatric cancers.
Professor of Pediatrics
Dr. Tan studies transcriptional regulation during normal development and disease. This involves the interplay of multiple transcription and epigenetic factors in a 3D chromosomal environment. Using experimental genomics and computational modeling, Dr. Tan investigates transcriptional regulatory networks underlying embryonic hematopoiesis, T cell differentiation, and pediatric leukemia.