* B.A. Reed College, 1994
* Ph.D. Harvard University, 2002

Research Interests:

* Transcriptional Regulatory Elements and Chromatin Structure
* Regulation of Genome Expression
* Expression of the Cancer Genome

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. There are four broad classes of transcriptional regulatory elements: enhancers, silencers, promoters and insulators. These elements are composed of a very short DNA sequences that serve as binding sites for transcription factors and are scattered throughout the genome. For each gene in the genome, there are usually multiple elements that control its expression. Conversely, each element may control multiple genes. 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 first identify these elements and determine how they are connected and controlled. By analyzing these transcriptional regulatory events in the entire genome, we hope to discover, reconstruct and analyze novel regulatory mechanisms and networks encoded in the genome. We also investigate how aberrant use and genetic or epigenetic alterations of these elements cause cancers. Our laboratory combines traditional molecular and biochemical methods with bioinformatics and high-throughput technologies to analyze these elements.

Current Research:

Chromatin domains and insulator function in cancers.

Insulators represent a unique class of regulatory elements that serves to segregate distinct genomic regions. Since insulators maintain proper genomic and chromatin domains, these elements represent a novel class of tumor suppressors. Recently, we have identified a large number of insulators in the human genome. We are now defining distinct functional classes of insulators and determining molecular mechanisms of insulator function. In addition, we are analyzing how alteration of these insulators contributes to cancers.

Characterization of Wnt-responsive enhancers in cancers.

Wnt signaling is critical for proper development and adult processes. Aberrant activation of Wnt signaling is thought be the initiating event in over 90% of colorectal cancers. We have defined a large set of Wnt-responsive enhancers that may contribute to initiation and maintenance of colon cancers. We are currently characterizing the target genes of these enhancers and analyzing their role in tumorigenesis.

Tae Hoon Kim*, Ziedulla K. Abdullaev, Andrew D. Smith, Keith A. Ching, Dmitri I. Loukinov, Roland D. Green, Michael Q. Zhang, Victor V. Lobanenkov and Bing Ren*. Analysis of the vertebrate insulator protein CTCF binding sites in the human genome. Cell 128:1231-1245 (2007). *corresponding authors

We are constantly considering and developing new methods for identifying and characterizing other regulatory elements. We employ various technologies that are available: high throughput sequencing, custom DNA microarrays, and various genomic libraries.