Tae Hoon Kim PhD
Associate Professor of Genetics; Member, Yale Cancer Center; Member, Yale Stem Cell Center
Transcription Regulation; Transcription Elongation; Transcription Insulation; Functional Genomics; Cancer Genomics; Epigenomics
Current ProjectsOur current research efforts span the following areas of investigation:
- systems biology of long range transcriptional regulation - genome-wide analysis of insulator function; analysis of chromosome topology and function
- functional genomics technology development - methods for investigating transcription rate and mRNA intermediates across the human genome
- cancer epigenome - structural alterations and epigenetic perturbations
The human genome is predominantly composed of non-protein coding sequences (>98%) whose function remains largely undefined. A significant portion of the non-coding DNA is believed to serve as transcriptional regulatory elements that control how and when the coding fraction of the genome is used by a cell. Precise expression of each gene during development is achieved by a coordinated action of multiple transcriptional regulatory elements. In order to reconstruct and understand genome expression, we systematically identify these elements and determine how they are connected and controlled. We also investigate how aberrant use of and alterations of these elements can cause cancers. Our laboratory combines traditional molecular and biochemical methods with bioinformatics and high-throughput functional genomics techniques to analyze these elements.
Extensive Research Description
We have two broad interests in transcription: transcription insulation and transcription elongation.
We study nuclear processes and mechanisms that segregate, fold and unfold chromosome fibers and disease causing changes that disrupt normal location, arrangement and interpretation of the human genome. Recently, we have determined the locations of a large number of insulators in the genome of primary fibroblasts. Insulators are an important class of transcriptional regulatory elements that affect gene expression by preventing the spread of heterochromatin and restricting how enhancers select their target promoters. We currently investigate the mechanisms involved in establishment and segregation of euchromatin and heterochromatin, and in folding of chromatin into higher order structures and how these insulation mechanisms are perturbed in cancer cells. We employ ChIP-seq (chromatin immunoprecipitation), 3C (chromosome conformation capture), GRO-seq (nascent RNA maping) and other functional genomics tools to define and analyze how the human genome is regulated. We utilize human cell lines and tissues (embryonic stem cells, primary fibroblasts, cancer/immortalized cells and primary cancer tissues). We couple these genome-wide experimental strategies with computational methods to systematically determine patterns, modes and mechanisms of genome expression.
Emerging functional genomic data suggest that transcription elongation is a critical step of oncogene expression in cancers. We are interested in defining pathways and networks that are critical for elongation step of oncogene transcription. We integrate global run-on sequencing (GRO-seq), copy number analysis, functional genomics and small molecule screening to achieve a comprehensive, systems level understanding of the transcription elongation control network at oncogenes and to develop strategies for selective inhibition of the network for cancer therapy.
In parallel to these areas of investigation, we pursue development of novel functional genomic techniques and approaches for our research.