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

Associate Professor in Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
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:

Mapping Epigenetic Memory of Exposure New To Observe (MEMENTO)

Administered By
Biomedical Engineering
Awarded By
Defense Advanced Research Projects Agency
Role
Co Investigator
Start Date
End Date

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

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

Administered By
Biomedical Engineering
Awarded By
National Science Foundation
Role
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

Publications:

Mapping the peripheral nervous system in the whole mouse via compressed sensing tractography.

Objective.The peripheral nervous system (PNS) connects the central nervous system with the rest of the body to regulate many physiological functions and is therapeutically targeted to treat diseases such as epilepsy, depression, intestinal dysmotility, chronic pain, and more. However, we still lack understanding of PNS innervation in most organs because the large span, diffuse nature, and small terminal nerve bundle fibers have precluded whole-organism, high resolution mapping of the PNS. We sought to produce a comprehensive peripheral nerve atlas for use in future interrogation of neural circuitry and selection of targets for neuromodulation.Approach.We used diffusion tensor magnetic resonance imaging (DT-MRI) with high-speed compressed sensing to generate a tractogram of the whole mouse PNS. The tractography generated from the DT-MRI data is validated using lightsheet microscopy on optically cleared, antibody stained tissue.Main results.Herein we demonstrate the first comprehensive PNS tractography in a whole mouse. Using this technique, we scanned the whole mouse in 28 h and mapped PNS innervation and fiber network in multiple organs including heart, lung, liver, kidneys, stomach, intestines, and bladder at 70µm resolution. This whole-body PNS tractography map has provided unparalleled information; for example, it delineates the innervation along the gastrointestinal tract by multiple sacral levels and by the vagal nerves. The map enabled a quantitative tractogram that revealed relative innervation of the major organs by each vertebral foramen as well as the vagus nerve.Significance.This novel high-resolution nerve atlas provides a potential roadmap for future neuromodulation therapies and other investigations into the neural circuits which drive homeostasis and disease throughout the body.
Authors
Garrett, A; Rakhilin, N; Wang, N; McKey, J; Cofer, G; Anderson, RB; Capel, B; Johnson, GA; Shen, X
MLA Citation
Garrett, Aliesha, et al. “Mapping the peripheral nervous system in the whole mouse via compressed sensing tractography.J Neural Eng, vol. 18, no. 4, June 2021. Pubmed, doi:10.1088/1741-2552/ac0089.
URI
https://scholars.duke.edu/individual/pub1481735
PMID
33979784
Source
pubmed
Published In
J Neural Eng
Volume
18
Published Date
DOI
10.1088/1741-2552/ac0089

Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19.

Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, yet the mechanisms governing this disparity remain incompletely understood. We carried out sex-balanced sampling of peripheral blood mononuclear cells from confirmed COVID-19 inpatients and outpatients, uninfected close contacts, and healthy controls for 36-color flow cytometry and single cell RNA-sequencing. Our results revealed a pronounced reduction of circulating mucosal associated invariant T (MAIT) cells in infected females. Integration of published COVID-19 airway tissue datasets implicate that this reduction represented a major wave of MAIT cell extravasation during early infection in females. Moreover, female MAIT cells possessed an immunologically active gene signature, whereas male counterparts were pro-apoptotic. Collectively, our findings uncover a female-specific protective MAIT profile, potentially shedding light on reduced COVID-19 susceptibility in females.
Authors
Yu, C; Littleton, S; Giroux, NS; Mathew, R; Ding, S; Kalnitsky, J; Yang, Y; Petzold, E; Chung, HA; Rivera, GO; Rotstein, T; Xi, R; Ko, ER; Tsalik, EL; Sempowski, GD; Denny, TN; Burke, TW; McClain, MT; Woods, CW; Shen, X; Saban, DR
MLA Citation
Yu, Chen, et al. “Mucosal Associated Invariant T (MAIT) Cell Responses Differ by Sex in COVID-19.Med (N Y), Apr. 2021. Pubmed, doi:10.1016/j.medj.2021.04.008.
URI
https://scholars.duke.edu/individual/pub1480358
PMID
33870241
Source
pubmed
Published In
Med (N Y)
Published Date
DOI
10.1016/j.medj.2021.04.008

The ALPK1/TIFA/NF-κB axis links a bacterial carcinogen to R-loop-induced replication stress.

Exposure of gastric epithelial cells to the bacterial carcinogen Helicobacter pylori causes DNA double strand breaks. Here, we show that H. pylori-induced DNA damage occurs co-transcriptionally in S-phase cells that activate NF-κB signaling upon innate immune recognition of the lipopolysaccharide biosynthetic intermediate β-ADP-heptose by the ALPK1/TIFA signaling pathway. DNA damage depends on the bi-functional RfaE enzyme and the Cag pathogenicity island of H. pylori, is accompanied by replication fork stalling and can be observed also in primary cells derived from gastric organoids. Importantly, H. pylori-induced replication stress and DNA damage depend on the presence of co-transcriptional RNA/DNA hybrids (R-loops) that form in infected cells during S-phase as a consequence of β-ADP-heptose/ ALPK1/TIFA/NF-κB signaling. H. pylori resides in close proximity to S-phase cells in the gastric mucosa of gastritis patients. Taken together, our results link bacterial infection and NF-κB-driven innate immune responses to R-loop-dependent replication stress and DNA damage.
Authors
Bauer, M; Nascakova, Z; Mihai, A-I; Cheng, PF; Levesque, MP; Lampart, S; Hurwitz, R; Pfannkuch, L; Dobrovolna, J; Jacobs, M; Bartfeld, S; Dohlman, A; Shen, X; Gall, AA; Salama, NR; Töpfer, A; Weber, A; Meyer, TF; Janscak, P; Müller, A
MLA Citation
Bauer, Michael, et al. “The ALPK1/TIFA/NF-κB axis links a bacterial carcinogen to R-loop-induced replication stress.Nature Communications, vol. 11, no. 1, Oct. 2020, p. 5117. Epmc, doi:10.1038/s41467-020-18857-z.
URI
https://scholars.duke.edu/individual/pub1462020
PMID
33037203
Source
epmc
Published In
Nature Communications
Volume
11
Published Date
Start Page
5117
DOI
10.1038/s41467-020-18857-z

MICRORNA SAFEGUARDING THE INFLAMMATORY COLON STEM CELL NICHE

Authors
MLA Citation
Shen, Xiling. “MICRORNA SAFEGUARDING THE INFLAMMATORY COLON STEM CELL NICHE.” Inflammatory Bowel Diseases, vol. 24, LIPPINCOTT WILLIAMS & WILKINS, 2018, pp. S27–S27.
URI
https://scholars.duke.edu/individual/pub1422259
Source
wos
Published In
Inflammatory Bowel Diseases
Volume
24
Published Date
Start Page
S27
End Page
S27

P076 MICRORNA SAFEGUARDING THE INFLAMMATORY COLON STEM CELL NICHE

Authors
MLA Citation
Shen, Xiling. “P076 MICRORNA SAFEGUARDING THE INFLAMMATORY COLON STEM CELL NICHE.” Gastroenterology, vol. 154, no. 1, Elsevier BV, 2018, pp. S39–S39. Crossref, doi:10.1053/j.gastro.2017.11.116.
URI
https://scholars.duke.edu/individual/pub1422258
Source
crossref
Published In
Gastroenterology
Volume
154
Published Date
Start Page
S39
End Page
S39
DOI
10.1053/j.gastro.2017.11.116