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:

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

An organotypic model recapitulating colon cancer microenvironment and metastasis

Administered By
Biomedical Engineering
Role
Principal Investigator
Start Date
End Date

T32-Diversity: NRSA Diversity Supplement Award

Administered By
Medicine, Gastroenterology
Awarded By
National Institutes of Health
Role
Co-Mentor
Start Date
End Date

Robust Control of the Stem Cell Niche

Administered By
Biomedical Engineering
Awarded By
National Institutes of Health
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.Journal of Neural Engineering, vol. 18, no. 4, June 2021. Epmc, doi:10.1088/1741-2552/ac0089.
URI
https://scholars.duke.edu/individual/pub1481735
PMID
33979784
Source
epmc
Published In
Journal of Neural Engineering
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

A Tissue Engineering Approach to Metastatic Colon Cancer.

Colon cancer remains the third most common cause of cancer in the US, and the third most common cause of cancer death. Worldwide, colon cancer is the second most common cause of cancer and cancer deaths. At least 25% of patients still present with metastatic disease, and at least 25-30% will develop metastatic colon cancer in the course of their disease. While chemotherapy and surgery remain the mainstay of treatment, understanding the fundamental cellular niche and mechanical properties that result in metastases would facilitate both prevention and cure. Advances in biomaterials, novel 3D primary human cells, modelling using microfluidics and the ability to alter the physical environment, now offers a unique opportunity to develop and test impactful treatment.
Authors
Sarvestani, SK; DeHaan, RK; Miller, PG; Bose, S; Shen, X; Shuler, ML; Huang, EH
MLA Citation
Sarvestani, Samaneh Kamali, et al. “A Tissue Engineering Approach to Metastatic Colon Cancer.Iscience, vol. 23, no. 11, Nov. 2020, p. 101719. Epmc, doi:10.1016/j.isci.2020.101719.
URI
https://scholars.duke.edu/individual/pub1465588
PMID
33205026
Source
epmc
Published In
Iscience
Volume
23
Published Date
Start Page
101719
DOI
10.1016/j.isci.2020.101719

DYNAMIC EPIGENETIC REPROGRAMMING ENABLES FUNCTIONAL DIVERSIFICATION OF HEPATOCYTES DURING LIVER REGENERATION

Authors
Chen, T; Oh, S-H; Gregory, SG; Shen, X; Diehl, AM
MLA Citation
URI
https://scholars.duke.edu/individual/pub1467632
Source
wos-lite
Published In
Hepatology (Baltimore, Md.)
Volume
72
Published Date
Start Page
119A
End Page
120A

Single cell transcriptomics of mouse kidney transplants reveals a myeloid cell pathway for transplant rejection.

Myeloid cells are increasingly recognized as major players in transplant rejection. Here, we used a murine kidney transplantation model and single cell transcriptomics to dissect the contribution of myeloid cell subsets and their potential signaling pathways to kidney transplant rejection. Using a variety of bioinformatic techniques, including machine learning, we demonstrate that kidney allograft-infiltrating myeloid cells followed a trajectory of differentiation from monocytes to proinflammatory macrophages, and they exhibited distinct interactions with kidney allograft parenchymal cells. While this process correlated with a unique pattern of myeloid cell transcripts, a top gene identified was Axl, a member of the receptor tyrosine kinase family Tyro3/Axl/Mertk (TAM). Using kidney transplant recipients with Axl gene deficiency, we further demonstrate that Axl augmented intragraft differentiation of proinflammatory macrophages, likely via its effect on the transcription factor Cebpb. This, in turn, promoted intragraft recruitment, differentiation, and proliferation of donor-specific T cells, and it enhanced early allograft inflammation evidenced by histology. We conclude that myeloid cell Axl expression identified by single cell transcriptomics of kidney allografts in our study plays a major role in promoting intragraft myeloid cell and T cell differentiation, and it presents a potentially novel therapeutic target for controlling kidney allograft rejection and improving kidney allograft survival.
Authors
Dangi, A; Natesh, NR; Husain, I; Ji, Z; Barisoni, L; Kwun, J; Shen, X; Thorp, EB; Luo, X
MLA Citation
Dangi, Anil, et al. “Single cell transcriptomics of mouse kidney transplants reveals a myeloid cell pathway for transplant rejection.Jci Insight, vol. 5, no. 20, Oct. 2020. Pubmed, doi:10.1172/jci.insight.141321.
URI
https://scholars.duke.edu/individual/pub1460803
PMID
32970632
Source
pubmed
Published In
Jci Insight
Volume
5
Published Date
DOI
10.1172/jci.insight.141321