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:

Intravital imaging of mouse embryos.

Embryonic development is a complex process that is unamenable to direct observation. In this study, we implanted a window to the mouse uterus to visualize the developing embryo from embryonic day 9.5 to birth. This removable intravital window allowed manipulation and high-resolution imaging. In live mouse embryos, we observed transient neurotransmission and early vascularization of neural crest cell (NCC)-derived perivascular cells in the brain, autophagy in the retina, viral gene delivery, and chemical diffusion through the placenta. We combined the imaging window with in utero electroporation to label and track cell division and movement within embryos and observed that clusters of mouse NCC-derived cells expanded in interspecies chimeras, whereas adjacent human donor NCC-derived cells shrank. This technique can be combined with various tissue manipulation and microscopy methods to study the processes of development at unprecedented spatiotemporal resolution.
Authors
Huang, Q; Cohen, MA; Alsina, FC; Devlin, G; Garrett, A; McKey, J; Havlik, P; Rakhilin, N; Wang, E; Xiang, K; Mathews, P; Wang, L; Bock, C; Ruthig, V; Wang, Y; Negrete, M; Wong, CW; Murthy, PKL; Zhang, S; Daniel, AR; Kirsch, DG; Kang, Y; Capel, B; Asokan, A; Silver, DL; Jaenisch, R; Shen, X
MLA Citation
Huang, Qiang, et al. “Intravital imaging of mouse embryos.Science, vol. 368, no. 6487, Apr. 2020, pp. 181–86. Pubmed, doi:10.1126/science.aba0210.
URI
https://scholars.duke.edu/individual/pub1436476
PMID
32273467
Source
pubmed
Published In
Science
Volume
368
Published Date
Start Page
181
End Page
186
DOI
10.1126/science.aba0210

An imprecise path to precision medicine.

Authors
MLA Citation
Shen, Xiling. “An imprecise path to precision medicine.Nature Medicine, vol. 26, no. 1, Jan. 2020, p. 14. Epmc, doi:10.1038/s41591-019-0718-6.
URI
https://scholars.duke.edu/individual/pub1428553
PMID
31932784
Source
epmc
Published In
Nature Medicine
Volume
26
Published Date
Start Page
14
DOI
10.1038/s41591-019-0718-6

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, p. 5647. 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

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

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, p. 13992. 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