Our lab is interested in Systems Biology of gene regulation. Gene expression variations play a major role in driving phenotypic variations. Because gene expression can be modulated at multiple levels, it is a challenging task to study gene regulatory systems. The advent of various functional genomics technologies increasingly allows us to interrogate the status of a cell's components and to determine how, when, and where these molecules interact with each other. On the other hand, the availability of a large number of sequenced genomes has enabled powerful comparative approaches to study a variety of biological questions. Our research takes advantage of the strength of Systems Biology and Comparative Genomics to understand gene regulation.
Within the broad area of gene regulation, we focus our effort on understanding gene regulatory networks that control: 1) stem cell phenotype (fate specification); and 2) disease development. These efforts will help us better understand how the different processes controlling gene expression are coordinated in the cell and deepen our knowledge of organismal development and disease processes. Towards this goal, we are conducting interdisciplinary research, combining wet-lab experiments and computation along the following two lines:
Model gene regulatory networks in development and disease
We are studying gene networks controlling hematopoietic stem cell fate and disease pathogenesis using functional genomic assays and computational modeling. In this biological context, we are pursuing the following projects:
i) Identify transcriptional enhancers that control stage-specific gene expression. We are developing computational tools to predict enhancers. We are also developing a high through-put assay to validate our computational predictions.
ii) Understand the interaction between transcription factor binding and chromatin modifications and its effect on gene expression during stem cell fate specification and pathogenesis.
iii) Integrate genomic and interactomic data to discover gene regulatory pathways during stem cell fate specification and pathogenesis.
Discover molecular networks as biomarkers for human diseases
Molecular interaction networks are increasingly serving as tools to unravel the basis of human diseases. We are developing network-based approaches to identifying disease-related sub-networks that can serve as biomarkers for the diagnosis and prognosis of diseases and as candidates for novel therapeutics.
Yu W, He B, Tan K: Identifying topologically associating domains and subdomains by Gaussian mixture model and proportion test. Nature Communications 8(1): 535, Sept 2017.
Li Y, Gao L, Hadland B, Tan K*, Speck NA*: CD27 marks murine embryonic hematopoietic stem cells and type II pre-hematopoietic stem cells. Blood 130(3): 372-376, July 2017.
He B, Xing S, Chen C, Gao P, Teng L, Shan Q, Gullicksrud JA, Martin MD, Yu S, Harty JT, Badovinac VP, Tan K*, Xue HH*: CD8+ T cells utilize highly dynamic enhancer repertoires and regulatory circuitry in response to infections. Immunity 45(6): 1341-1354, Dec 2016.
He, B and Tan K: Understanding transcriptional regulatory networks using computational models. Current Opinion in Genes & Development 37: 101-108, Mar 2016.
Cao Z, Chen C, He B, Tan K* and Lu C*: A microfluidic device for profiling genome-wide histone modifications using 100 cells. Nature Methods 12(10): 959-962, Oct 2015.
Cai X, Gao L, Teng L, Ge J, Oo Z, Kumar A, Gilliland GD, Mason PJ, Tan K and Speck NA.: Runx1 deficiency decreases ribosome biogenesis and confers stress resistance to hematopoietic stem and progenitor Cells. Cell Stem Cell 17(2): 165-77, Aug 2015.
Teng L, He B, Wang J, and Tan K. : 4DGenome: a comprehensive database of chromatin interactions. Bioinformatics 31(15): 2560-4, Aug 2015.
Ma X, Gao Long, Lee CF, Gao P, Karamanlidis G, Garcia-Menendez L, Tian R and Tan K: Revealing pathway dynamics in heart diseases by analyzing multiple differential networks. PLoS Computational Biology 11(6): e1004332, Jun 2015.
He B, Chen C, Teng L, and Tan K.: Global view of enhancer-promoter interactome in human cells. Proc Natl Acad Sci 111(21): E2191-9, May 2014.
Steinke FC, Yu S, Zhou X, He B, Yang W, Zhou B, Kawamoto H, Zhu J, Tan K and Xue
HH.: TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T cell fate and interact with Runx3 to silence Cd4 in CD8(+) T cells. Nature Immunology 15(7): 646-56, Jul 2014.
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Last updated: 09/16/2017
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