Xiling Shen

Overview:

Dr. Shen’s research interests lie at precision medicine and systems biology. His lab integrates engineering, computational and biological techniques to study cancer, stem cells, microbiota and the nervous system in the gut. This multidisciplinary work has been instrumental in initiating several translational clinical trials in precision therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP) and a core member of the Center for Genomics and Computational Biology (GCB).

Positions:

Hawkins Family Associate Professor

Biomedical Engineering
Pratt School of Engineering

Associate Professor in the Department of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Associate Professor in the Department of Electrical and Computer Engineering

Electrical and Computer Engineering
Pratt School of Engineering

Associate Professor in Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Education:

B.Sc. 2001

Stanford University

M.Sc. 2001

Stanford University

Ph.D. 2008

Stanford University

Grants:

A comprehensive research resource to define mechanisms underlying microbial regulation of host metabolism in pediatric obesity and obesity-targeted therapeutics

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Epigenomic Reprogramming in Patient Derived Models of Colorectal Cancer

Administered By
Biomedical Engineering
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Engineering Technologies to Determine Causal Relationships Between Chromatin Structure and Gene Regulation

Administered By
Biomedical Engineering
Awarded By
National Science Foundation
Role
Co-Principal Investigator
Start Date
End Date

An organotypic model recapitulating colon cancer microenvironment and metastasis

Administered By
Biomedical Engineering
Role
Principal Investigator
Start Date
End Date

Functional mapping of efferent gut neuroepithelial circuits

Administered By
Biomedical Engineering
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Integrated chromatin and transcriptomic profiling of patient-derived colon cancer organoids identifies personalized drug targets to overcome oxaliplatin resistance

© 2019 Chongqing Medical University Colorectal cancer is a leading cause of cancer deaths. Most colorectal cancer patients eventually develop chemoresistance to the current standard-of-care therapies. Here, we used patient-derived colorectal cancer organoids to demonstrate that resistant tumor cells undergo significant chromatin changes in response to oxaliplatin treatment. Integrated transcriptomic and chromatin accessibility analyses using ATAC-Seq and RNA-Seq identified a group of genes associated with significantly increased chromatin accessibility and upregulated gene expression. CRISPR/Cas9 silencing of fibroblast growth factor receptor 1 (FGFR1) and oxytocin receptor (OXTR) helped overcome oxaliplatin resistance. Similarly, treatment with oxaliplatin in combination with an FGFR1 inhibitor (PD166866) or an antagonist of OXTR (L-368,899) suppressed chemoresistant organoids. However, oxaliplatin treatment did not activate either FGFR1 or OXTR expression in another resistant organoid, suggesting that chromatin accessibility changes are patient-specific. The use of patient-derived cancer organoids in combination with transcriptomic and chromatin profiling may lead to precision treatments to overcome chemoresistance in colorectal cancer.
Authors
Tung, KL; Chen, KY; Negrete, M; Chen, T; Safi, A; Aljamal, AA; Song, L; Crawford, GE; Ding, S; Hsu, DS; Shen, X
MLA Citation
URI
https://scholars.duke.edu/individual/pub1423274
Source
scopus
Published In
Genes and Diseases
Published Date
DOI
10.1016/j.gendis.2019.10.012

An intravital window to image the colon in real time.

Intravital microscopy is a powerful technique to observe dynamic processes with single-cell resolution in live animals. No intravital window has been developed for imaging the colon due to its anatomic location and motility, although the colon is a key organ where the majority of microbiota reside and common diseases such as inflammatory bowel disease, functional gastrointestinal disorders, and colon cancer occur. Here we describe an intravital murine colonic window with a stabilizing ferromagnetic scaffold for chronic imaging, minimizing motion artifacts while maximizing long-term survival by preventing colonic obstruction. Using this setup, we image fluorescently-labeled stem cells, bacteria, and immune cells in live animal colons. Furthermore, we image nerve activity via calcium imaging in real time to demonstrate that electrical sacral nerve stimulation can activate colonic enteric neurons. The simple implantable apparatus enables visualization of live processes in the colon, which will open the window to a broad range of studies.
Authors
Rakhilin, N; Garrett, A; Eom, C-Y; Chavez, KR; Small, DM; Daniel, AR; Kaelberer, MM; Mejooli, MA; Huang, Q; Ding, S; Kirsch, DG; Bohórquez, DV; Nishimura, N; Barth, BB; Shen, X
MLA Citation
Rakhilin, Nikolai, et al. “An intravital window to image the colon in real time..” Nat Commun, vol. 10, no. 1, Dec. 2019. Pubmed, doi:10.1038/s41467-019-13699-w.
URI
https://scholars.duke.edu/individual/pub1423159
PMID
31827103
Source
pubmed
Published In
Nature Communications
Volume
10
Published Date
Start Page
5647
DOI
10.1038/s41467-019-13699-w

Author Correction: Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Authors
Choi, J; Rakhilin, N; Gadamsetty, P; Joe, DJ; Tabrizian, T; Lipkin, SM; Huffman, DM; Shen, X; Nishimura, N
MLA Citation
Choi, Jiahn, et al. “Author Correction: Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging..” Scientific Reports, vol. 9, no. 1, Sept. 2019. Epmc, doi:10.1038/s41598-019-43805-3.
URI
https://scholars.duke.edu/individual/pub1414999
PMID
31570744
Source
epmc
Published In
Scientific Reports
Volume
9
Published Date
Start Page
13992
DOI
10.1038/s41598-019-43805-3

Physiological responses to sacral nerve stimulation in rodent colon

Authors
Barth, BB; Grill, WM; Shen, X
MLA Citation
Barth, B. B., et al. “Physiological responses to sacral nerve stimulation in rodent colon.” Neurogastroenterology and Motility, vol. 31, WILEY, 2019.
URI
https://scholars.duke.edu/individual/pub1406602
Source
wos
Published In
Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society
Volume
31
Published Date

Mapping the microbial interactome: Statistical and experimental approaches for microbiome network inference.

IMPACT STATEMENT:This review provides a comprehensive description of experimental and statistical tools used for network analyses of the human gut microbiome. Understanding the system dynamics of microbial interactions may lead to the improvement of therapeutic approaches for managing microbiome-associated diseases. Microbiome network inference tools have been developed and applied to both cross-sectional and longitudinal experimental designs, as well as to multi-omic datasets, with the goal of untangling the complex web of microbe-host, microbe-environmental, and metabolism-mediated microbial interactions. The characterization of these interaction networks may lead to a better understanding of the systems dynamics of the human gut microbiome, augmenting our knowledge of the microbiome's role in human health, and guiding the optimization of effective, precise, and rational therapeutic strategies for managing microbiome-associated disease.
Authors
Dohlman, AB; Shen, X
MLA Citation
Dohlman, Anders B., and Xiling Shen. “Mapping the microbial interactome: Statistical and experimental approaches for microbiome network inference..” Experimental Biology and Medicine (Maywood, N.J.), vol. 244, no. 6, Apr. 2019, pp. 445–58. Epmc, doi:10.1177/1535370219836771.
URI
https://scholars.duke.edu/individual/pub1374826
PMID
30880449
Source
epmc
Published In
Experimental Biology and Medicine
Volume
244
Published Date
Start Page
445
End Page
458
DOI
10.1177/1535370219836771