Faculty

Kai Tan, PhD

faculty photo
Associate Professor of Pediatrics
Department: Pediatrics

Contact information
The Children's Hospital of Philadelphia
Division of Oncology, Department of Pediatrics
3501 Civic Center Blvd.
4004 Colket Translational Research Bldg.
Philadelphia, PA 19104
Office: 267-425-0050
Lab: 267-425-0058
Education:
B.S. (Biochemistry)
Beloit College, 1997.
Ph.D. (Computational Biology)
Washington University in St. Louis, 2004.
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Description of Research Expertise

Gene regulation plays a fundamental role in cellular development and cancer. Our lab uses genomics and systems biology approaches to understand the gene regulatory factors underlying cellular processes. We take snapshots of the regulatory systems using bulk and single-cell omics and imaging assays, and develop computational algorithms to integrate data and generate testable models of gene regulatory pathways in model systems.

Understanding the molecular basis of therapeutic resistance in cancer

We have a number of ongoing projects investigating the molecular basis of oncogenesis and therapy resistance in cancer cells. Some highlights are:

1) Generation of a bulk and single-cell multi-omic atlas of pediatric cancer at multiple therapeutic time points
2) Identification of novel combination therapies by understanding disease-perturbed gene networks
3) Understanding the cellular adaptations of cancer cells to targeted therapy and immunotherapy through novel systems biology approaches

Unraveling the gene regulatory factors involved in cellular development

We are studying gene regulatory networks controlling the embryonic origin of hematopoietic stem cells, differentiation of T-cells, and pediatric cancers. Specific questions we ask include:

1) What are the key regulators and cis-regulatory elements that control cell/tissue-specific gene expression in these systems?
2) How does the 3-dimensional genome organization controls cell/tissue-specific gene expression in these systems?
3) What are the mutations in the cis-regulatory DNA sequences that confer disease risk in these systems?
4) What are the signaling pathways that mediate cell-cell communications in in these systems?

Development of computational methods to interpret high-dimensional and single-cell transcriptomics, proteomics, and epigenomics data

We develop data-driven methods to integrate multi-omics data using network biology and principled machine learning. We generate large data sources using methods such as bulk and single-cell RNA-Seq, ATAC-Seq, Hi-C, and multiplexed fluorescent imaging. We develop computational methods to integrate these data sources and model the gene regulatory architecture that underlies cellular fate and disease. Ongoing projects include:

1) Development of network-based approaches to identify disease-perturbed pathways and critical regulatory nodes for the diagnosis and prognosis of diseases, and to identify candidates for novel therapeutics
2) Integration of single-cell transcriptomics and epigenomics to characterize the sequence of gene regulatory events leading to cellular differentiation and cancer
3) Understanding the impact of non-coding somatic variation, including copy number alterations and structural variation, in pediatric cancer

Selected Publications

Chen GM, Azzam A, Ding Y, Barrett DM, Grupp SA, Tan K.: Dissecting the tumor-immune landscape in chimeric antigen receptor T-cell therapy: key challenges and opportunities for a systems immunology approach. Clinical Cancer Research Mar 2020.

Chen C, Yu W, Tober J, Gao P, He B, Lee K, Trieu T, Blobel G, Speck N, Tan K.: Spatial genome re-organization between fetal and adult hematopoietic stem cells. Cell Reports Dec 2019.

Hu Y, Gao L, Chen C, Ding Y, Wen X, Wang B, and Tan K: Optimal control nodes in disease-perturbed networks as targets for combination therapy. Nature Communications 10(1): 2180, May 2019.

Peng T, Zhu Q, Yin P, Tan K: Single-cell RNA-Seq imputation constrained by bulk RNA-Seq data. Genome Biology 20(1): 88, May 2019.

Gao P, Uzun Y, He B, Salamati S, Coffey JKM, Taslikian E, Tan K.: Novel risk variants disrupting enhancers of TH1 and TREG cells in type 1 diabetes. PNAS 116(15): 7581-7590, Apr 2019.

Gao L, Uzun Y, Gao P, He B, Ma X, Wang J, Han S, Tan K.: Identifying noncoding risk variants using disease-relevant gene regulatory networks Nature Communications 9(1): 702, Feb 2018.

Tober J, Maijenburg MW, Y, Gao L, Hadland BK, Gao P, Clarke R, Bernstein I, Keller G, Tan K*, Speck NA*.: Maturation of hematopoietic stem cells from prehematopoietic stem cells is accompanied by up-regulation of PD-L1. Journal of Experimental Medicine 215(2): 645-659, Feb 2018 Notes: * Co-corresponding author.

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 Notes: * Co-corresponding author.

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 Notes: * Co-corresponding author.

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 Notes: * Co-corresponding author.

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Last updated: 06/02/2020
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