Scholars@Duke
Xiling Shen

Xiling Shen

Adjunct Professor in the Department of Pathology
Pathology
xiling.shen@duke.edu
2167 CIEMAS, 101 Science Dr, Box 3382, Durham, NC 27708
2167 CIEMAS, 101 Science Drive, Box 3382, Durham, NC 27708

Selected Publications

Patient-Derived Organoids as Therapy Screening Platforms in Cancer Patients.

Journal Article Adv Healthc Mater · August 2024 Patient-derived organoids (PDOs) developed ex vivo and in vitro are increasingly used for therapeutic screening. They provide a more physiologically relevant model for drug discovery and development compared to traditional cell lines. However, several chal ... Full text Link to item Cite

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.

Conference Adv Sci (Weinh) · April 2024 Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the trans ... Full text Link to item Cite

Longitudinal intravital imaging of mouse placenta.

Journal Article Sci Adv · March 22, 2024 Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enabl ... Full text Open Access Link to item Cite

Tissue-resident memory T cell signatures from single-cell analysis associated with better melanoma prognosis.

Journal Article iScience · March 15, 2024 Tissue-resident memory T cells (TRM) are a specialized T cell population residing in peripheral tissues. The presence and potential impact of TRM in the tumor immune microenvironment (TIME) remain to be elucidated. Here, we systematically investigated the ... Full text Link to item Cite

Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations.

Journal Article Cancers (Basel) · January 29, 2024 For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of p ... Full text Link to item Cite

Activation of cytotoxic lymphocytes through CD6 enhances killing of cancer cells.

Journal Article Cancer Immunol Immunother · January 27, 2024 Immune checkpoint inhibitors (ICIs) have demonstrated efficacy and improved survival in a growing number of cancers. Despite their success, ICIs are associated with immune-related adverse events that can interfere with their use. Therefore, safer approache ... Full text Link to item Cite

Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection.

Journal Article iScience · January 19, 2024 To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined si ... Full text Open Access Link to item Cite

The KRAS tour: Studying metabolic reprogramming in isogenic pancreatic cancer organoids.

Journal Article Cell Stem Cell · January 4, 2024 Using an isogenic organoid platform to model pancreatic cancer, Duan et al. establish an important link between mutant KRAS and cholesterol metabolism and identify perhexiline maleate as a possible therapeutic to target this relationship. ... Full text Link to item Cite

Data from A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer

Other · April 3, 2023 <div>Abstract<p>Colorectal cancer is the third most common cancer in the United States and responsible for over 50,000 deaths each year. Therapeutic options for advanced colorectal cancer are limited, and there remains an unmet clinical ... Full text Cite

Data from A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer

Other · April 3, 2023 <div>Abstract<p>Colorectal cancer is the third most common cancer in the United States and responsible for over 50,000 deaths each year. Therapeutic options for advanced colorectal cancer are limited, and there remains an unmet clinical ... Full text Cite

A path to translation: How 3D patient tumor avatars enable next generation precision oncology.

Journal Article Cancer Cell · December 12, 2022 3D patient tumor avatars (3D-PTAs) hold promise for next-generation precision medicine. Here, we describe the benefits and challenges of 3D-PTA technologies and necessary future steps to realize their potential for clinical decision making. 3D-PTAs require ... Full text Link to item Cite

Thioredoxin-1 regulates self-renewal and differentiation of murine hematopoietic stem cells through p53 tumor suppressor.

Journal Article Exp Hematol Oncol · October 31, 2022 BACKGROUND: Thioredoxin-1 (TXN1) is one of the major cellular antioxidants in mammals and is involved in a wide range of physiological cellular responses. However, little is known about the roles and the underlying molecular mechanisms of TXN1 in the regul ... Full text Link to item Cite

Using genetically encoded fluorescent biosensors to interrogate ovarian cancer metabolism.

Journal Article J Ovarian Res · October 20, 2022 BACKGROUND: Epithelial ovarian cancer (OC) is the most lethal gynecological malignancy and patients present with significant metastatic burden, particularly to the adipose-rich microenvironment of the omentum. Recent evidence has highlighted the importance ... Full text Link to item Cite

Three-Dimensional Deep-Tissue Functional and Molecular Imaging by Integrated Photoacoustic, Ultrasound, and Angiographic Tomography (PAUSAT).

Journal Article IEEE Trans Med Imaging · October 2022 Non-invasive small-animal imaging technologies, such as optical imaging, magnetic resonance imaging and x -ray computed tomography, have enabled researchers to study normal biological phenomena or disease progression in their native conditions. However, ex ... Full text Link to item Cite

Blocking CCL8-CCR8-Mediated Early Allograft Inflammation Improves Kidney Transplant Function.

Journal Article J Am Soc Nephrol · October 2022 BACKGROUND: In kidney transplantation, early allograft inflammation impairs long-term allograft function. However, precise mediators of early kidney allograft inflammation are unclear, making it challenging to design therapeutic interventions. METHODS: We ... Full text Open Access Link to item Cite

Rapid tissue prototyping with micro-organospheres.

Journal Article Stem Cell Reports · September 13, 2022 In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be establish ... Full text Open Access Link to item Cite

A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors.

Journal Article Cell · September 2022 Fungal microorganisms (mycobiota) comprise a small but immunoreactive component of the human microbiome, yet little is known about their role in human cancers. Pan-cancer analysis of multiple body sites revealed tumor-associated mycobiomes at up to 1 funga ... Full text Cite

Differential chromatin accessibility in peripheral blood mononuclear cells underlies COVID-19 disease severity prior to seroconversion.

Journal Article Sci Rep · July 9, 2022 SARS-CoV-2 infection triggers profound and variable immune responses in human hosts. Chromatin remodeling has been observed in individuals severely ill or convalescing with COVID-19, but chromatin remodeling early in disease prior to anti-spike protein IgG ... Full text Open Access Link to item Cite

Glycerate from intestinal fructose metabolism induces islet cell damage and glucose intolerance.

Journal Article Cell Metab · July 5, 2022 Dietary fructose, especially in the context of a high-fat western diet, has been linked to type 2 diabetes. Although the effect of fructose on liver metabolism has been extensively studied, a significant portion of the fructose is first metabolized in the ... Full text Link to item Cite

G6PD inhibition sensitizes ovarian cancer cells to oxidative stress in the metastatic omental microenvironment.

Journal Article Cell Rep · June 28, 2022 Ovarian cancer (OC) is the most lethal gynecological malignancy, with aggressive metastatic disease responsible for the majority of OC-related deaths. In particular, OC tumors preferentially metastasize to and proliferate rapidly in the omentum. Here, we s ... Full text Link to item Cite

Patient-derived micro-organospheres enable clinical precision oncology.

Journal Article Cell Stem Cell · June 2, 2022 Patient-derived xenografts (PDXs) and patient-derived organoids (PDOs) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here, we used d ... Full text Open Access Link to item Cite

Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy.

Journal Article Light Sci Appl · May 17, 2022 High-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research. High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks, an ... Full text Open Access Link to item Cite

DAMPs/PAMPs induce monocytic TLR activation and tolerance in COVID-19 patients; nucleic acid binding scavengers can counteract such TLR agonists.

Journal Article Biomaterials · April 2022 Millions of COVID-19 patients have succumbed to respiratory and systemic inflammation. Hyperstimulation of toll-like receptor (TLR) signaling is a key driver of immunopathology following infection by viruses. We found that severely ill COVID-19 patients in ... Full text Open Access Link to item Cite

Mycobacterial infection aggravates Helicobacter pylori-induced gastric preneoplastic pathology by redirection of de novo induced Treg cells.

Journal Article Cell Rep · February 8, 2022 The two human pathogens Helicobacter pylori and Mycobacterium tuberculosis (Mtb) co-exist in many geographical areas of the world. Here, using a co-infection model of H. pylori and the Mtb relative M. bovis bacillus Calmette-Guérin (BCG), we show that both ... Full text Link to item Cite

Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity.

Journal Article Dev Cell · February 7, 2022 Oncogenic Kras induces a hyper-proliferative state that permits cells to progress to neoplasms in diverse epithelial tissues. Depending on the cell of origin, this also involves lineage transformation. Although a multitude of downstream factors have been i ... Full text Open Access Link to item Cite

Slow nucleosome dynamics set the transcriptional speed limit and induce RNA polymerase II traffic jams and bursts.

Journal Article PLoS Comput Biol · February 2022 Nucleosomes are recognized as key regulators of transcription. However, the relationship between slow nucleosome unwrapping dynamics and bulk transcriptional properties has not been thoroughly explored. Here, an agent-based model that we call the dynamic d ... Full text Link to item Cite

Deep learning segmentation of glomeruli on kidney donor frozen sections.

Journal Article J Med Imaging (Bellingham) · November 2021 Purpose: Recent advances in computational image analysis offer the opportunity to develop automatic quantification of histologic parameters as aid tools for practicing pathologists. We aim to develop deep learning (DL) models to quantify nonsclerotic and s ... Full text Link to item Cite

Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF-PU.1-DPP4 Axis.

Journal Article Adv Sci (Weinh) · October 2021 Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation ... Full text Open Access Link to item Cite

Promises and Challenges of Organoid-Guided Precision Medicine.

Journal Article Med · September 10, 2021 Organoids are self-organizing, expanding 3D cultures derived from stem cells. Using tissue derived from patients, these miniaturized models recapitulate various aspects of patient physiology and disease phenotypes including genetic profiles and drug sensit ... Full text Link to item Cite

Mucosal-associated invariant T cell responses differ by sex in COVID-19.

Journal Article Med · June 11, 2021 BACKGROUND: Sexual dimorphisms in immune responses contribute to coronavirus disease 2019 (COVID-19) outcomes, but the mechanisms governing this disparity remain incompletely understood. METHODS: We carried out sex-balanced sampling of peripheral blood mon ... Full text Open Access Link to item Cite

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

Journal Article J Neural Eng · June 8, 2021 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, chr ... Full text Link to item Cite

Living fabrication of functional semi-interpenetrating polymeric materials.

Journal Article Nat Commun · June 8, 2021 Cell-mediated living fabrication has great promise for generating materials with versatile, programmable functions. Here, we demonstrate the engineering of living materials consisting of semi-interpenetrating polymer networks (sIPN). The fabrication proces ... Full text Link to item Cite

An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility.

Journal Article Genome Med · May 17, 2021 BACKGROUND: While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challeng ... Full text Open Access Link to item Cite

The frontier of live tissue imaging across space and time.

Journal Article Cell Stem Cell · April 1, 2021 What you see is what you get-imaging techniques have long been essential for visualization and understanding of tissue development, homeostasis, and regeneration, which are driven by stem cell self-renewal and differentiation. Advances in molecular and tis ... Full text Link to item Cite

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

Journal Article Genes Dis · March 2021 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 tum ... Full text Link to item Cite

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery.

Journal Article Nat Commun · February 17, 2021 SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral bloo ... Full text Open Access Link to item Cite

The cancer microbiome atlas: a pan-cancer comparative analysis to distinguish tissue-resident microbiota from contaminants.

Journal Article Cell Host Microbe · February 10, 2021 Studying the microbial composition of internal organs and their associations with disease remains challenging due to the difficulty of acquiring clinical biopsies. We designed a statistical model to analyze the prevalence of species across sample types fro ... Full text Link to item Cite

Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity.

Journal Article Nat Commun · January 11, 2021 The pathogenesis of ulcerative colitis (UC), a major type of inflammatory bowel disease, remains unknown. No model exists that adequately recapitulates the complexity of clinical UC. Here, we take advantage of induced pluripotent stem cells (iPSCs) to deve ... Full text Link to item Cite

An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility.

Journal Article medRxiv · December 22, 2020 While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods a ... Full text Link to item Cite

Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity.

Journal Article bioRxiv · December 9, 2020 SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 physiology. ... Full text Open Access Link to item Cite

A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer.

Journal Article Mol Cancer Ther · December 2020 Colorectal cancer is the third most common cancer in the United States and responsible for over 50,000 deaths each year. Therapeutic options for advanced colorectal cancer are limited, and there remains an unmet clinical need to identify new treatments for ... Full text Link to item Cite

A Tissue Engineering Approach to Metastatic Colon Cancer.

Journal Article iScience · November 20, 2020 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 metastat ... Full text Link to item Cite

Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration.

Journal Article JCI Insight · November 19, 2020 Adult liver has enormous regenerative capacity; it can regenerate after losing two-thirds of its mass while sustaining essential metabolic functions. How the liver balances dual demands for increased proliferative activity with maintenance of organ functio ... Full text Link to item Cite

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

Journal Article JCI Insight · October 15, 2020 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 pathwa ... Full text Open Access Link to item Cite

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

Journal Article Nat Commun · October 9, 2020 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 imm ... Full text Link to item Cite

Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer.

Journal Article BMC Cancer · June 24, 2020 BACKGROUND: Metastatic colorectal cancer (CRC) continues to be a major health problem, and current treatments are primarily for disease control and palliation of symptoms. In this study, we developed a precision medicine strategy to discover novel therapeu ... Full text Link to item Cite

Intravital imaging of mouse embryos.

Journal Article Science · April 10, 2020 Featured Publication 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 manip ... Full text Open Access Link to item Cite

An imprecise path to precision medicine.

Journal Article Nat Med · January 2020 Full text Link to item Cite

An intravital window to image the colon in real time.

Journal Article Nat Commun · December 11, 2019 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 org ... Full text Link to item Cite

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

Journal Article Sci Rep · September 30, 2019 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. ... Full text Link to item Cite

Physiological responses to sacral nerve stimulation in rodent colon

Conference NEUROGASTROENTEROLOGY AND MOTILITY · August 1, 2019 Link to item Cite

Author Correction: A recellularized human colon model identifies cancer driver genes.

Journal Article Nat Biotechnol · July 2019 An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Full text Link to item Cite

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

Journal Article Exp Biol Med (Maywood) · April 2019 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 ... Full text Open Access Link to item Cite

Exploitation of Synthetic mRNA To Drive Immune Effector Cell Recruitment and Functional Reprogramming In Vivo.

Journal Article J Immunol · January 15, 2019 Therapeutic strategies based on in vitro-transcribed mRNA (IVT) are attractive because they avoid the permanent signature of genomic integration that is associated with DNA-based therapy and result in the transient production of proteins of interest. To da ... Full text Open Access Link to item Cite

SENP3-mediated host defense response contains HBV replication and restores protein synthesis.

Journal Article PLoS One · 2019 Certain organs are capable of containing the replication of various types of viruses. In the liver, infection of Hepatitis B virus (HBV), the etiological factor of Hepatitis B and hepatocellular carcinoma (HCC), often remains asymptomatic and leads to a ch ... Full text Link to item Cite

Agent-Based Modelling to Delineate Spatiotemporal Control Mechanisms of the Stem Cell Niche.

Journal Article Methods Mol Biol · 2019 Agent-based modelling (ABM) offers a framework to realistically couple subcellular signaling pathways to cellular behavior and macroscopic tissue organization. However, these models have been previously inaccessible to many systems biologists due to the di ... Full text Link to item Cite

miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis.

Journal Article Elife · December 13, 2018 Inflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the microRNA miR-34a acts as a central safeguard to pr ... Full text Link to item Cite

A gut-brain neural circuit for nutrient sensory transduction.

Journal Article Science · September 21, 2018 Featured Publication The brain is thought to sense gut stimuli only via the passive release of hormones. This is because no connection has been described between the vagus and the putative gut epithelial sensor cell-the enteroendocrine cell. However, these electrically excitab ... Full text Link to item Cite

Opportunities and Challenges for Single-Unit Recordings from Enteric Neurons in Awake Animals.

Journal Article Micromachines (Basel) · August 25, 2018 Advanced electrode designs have made single-unit neural recordings commonplace in modern neuroscience research. However, single-unit resolution remains out of reach for the intrinsic neurons of the gastrointestinal system. Single-unit recordings of the ent ... Full text Link to item Cite

Computational motility models of neurogastroenterology and neuromodulation.

Journal Article Brain Res · August 15, 2018 The success of neuromodulation therapies, particularly in the brain, spinal cord, and peripheral nerves, has been greatly aided by computational, biophysical models. However, treating gastrointestinal disorders with electrical stimulation has been much les ... Full text Link to item Cite

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

Journal Article Sci Rep · July 20, 2018 Despite the continuous renewal and turnover of the small intestinal epithelium, the intestinal crypt maintains a 'soccer ball-like', alternating pattern of stem and Paneth cells at the base of the crypt. To study the robustness of the alternating pattern, ... Full text Link to item Cite

Spatial Patterning from an Integrated Wnt/β-catenin and Notch/Delta Gene Circuit.

Journal Article Annu Int Conf IEEE Eng Med Biol Soc · July 2018 Classically, the Wnt/β-catenin and Notch /Delta signaling pathways were thought to operate through separate mechanisms, performing distinct roles in tissue patterning. However, it has been shown that b-catenin activates transcription of Hesl, a signaling i ... Full text Link to item Cite

Single-Cell Transcriptomics Reveals Heterogeneity and Drug Response of Human Colorectal Cancer Organoids.

Journal Article Annu Int Conf IEEE Eng Med Biol Soc · July 2018 Organoids are three-dimensional cell cultures that mimic organ functions and structures. The organoid model has been developed as a versatile in vitro platform for stem cell biology and diseases modeling. Tumor organoids are shown to share ~ 90% of genetic ... Full text Open Access Link to item Cite

Microbiota of Inflammatory Bowel Disease Models.

Conference Annu Int Conf IEEE Eng Med Biol Soc · July 2018 Gut microbiome plays an important role in inflammatory bowel disease (IBD), a group of intestinal chronic inflammation conditions that affect a large population. The animal models of IBD have long been established on basis of pathological features, but the ... Full text Link to item Cite

Abstract 5479: Targeting fructose-induced metabolic reprogramming in liver metastasis

Conference Cancer Research · July 1, 2018 AbstractPrimary tumors gradually accumulate genetic alterations and are influenced by their microenvironment until they acquire the ability to metastasize to distant organs. Typical of this process, colorect ... Full text Cite

Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.

Journal Article Cell Metab · June 5, 2018 Featured Publication Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we sh ... Full text Link to item Cite

Prometheus revisited.

Journal Article J Clin Invest · June 1, 2018 The liver's extraordinary ability to regenerate has been known since the myth of Prometheus, but the mechanisms involved are still being discovered. Various small animal models have been used in this quest. Two of the most popular include partial hepatecto ... Full text Link to item Cite

SENSORY SYNAPTIC TRANSDUCTION FROM GUT TO BRAIN

Conference GASTROENTEROLOGY · May 1, 2018 Link to item Cite

Radical and lunatic fringes modulate notch ligands to support mammalian intestinal homeostasis.

Journal Article Elife · April 9, 2018 Notch signalling maintains stem cell regeneration at the mouse intestinal crypt base and balances the absorptive and secretory lineages in the upper crypt and villus. Here we report the role of Fringe family of glycosyltransferases in modulating Notch acti ... Full text Link to item Cite

Matrix metalloproteinase inhibitors enhance the efficacy of frontline drugs against Mycobacterium tuberculosis.

Journal Article PLoS Pathog · April 2018 Mycobacterium tuberculosis (Mtb) remains a grave threat to world health with emerging drug resistant strains. One prominent feature of Mtb infection is the extensive reprogramming of host tissue at the site of infection. Here we report that inhibition of m ... Full text Link to item Cite

MICRORNA SAFEGUARDING THE INFLAMMATORY COLON STEM CELL NICHE

Conference INFLAMMATORY BOWEL DISEASES · February 1, 2018 Link to item Cite

Electrical stimulation of gut motility guided by an in silico model.

Journal Article J Neural Eng · December 2017 OBJECTIVE: Neuromodulation of the central and peripheral nervous systems is becoming increasingly important for treating a diverse set of diseases-ranging from Parkinson's Disease and epilepsy to chronic pain. However, neuromodulation of the gastrointestin ... Full text Link to item Cite

The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation.

Journal Article Nature · September 14, 2017 The type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 have important roles in stimulating innate and adaptive immune responses that are required for resistance to helminth infection, promotion of allergic inflammation, metabolic homeostasis and tis ... Full text Link to item Cite

Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis.

Journal Article Proc Natl Acad Sci U S A · May 2, 2017 According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given pre ... Full text Link to item Cite

A Notch positive feedback in the intestinal stem cell niche is essential for stem cell self-renewal.

Journal Article Mol Syst Biol · April 28, 2017 The intestinal epithelium is the fastest regenerative tissue in the body, fueled by fast-cycling stem cells. The number and identity of these dividing and migrating stem cells are maintained by a mosaic pattern at the base of the crypt. How the underlying ... Full text Link to item Cite

Fucosylation Deficiency in Mice Leads to Colitis and Adenocarcinoma.

Journal Article Gastroenterology · January 2017 BACKGROUND & AIMS: De novo synthesis of guanosine diphosphate (GDP)-fucose, a substrate for fucosylglycans, requires sequential reactions mediated by GDP-mannose 4,6-dehydratase (GMDS) and GDP-4-keto-6-deoxymannose 3,5-epimerase-4-reductase (FX or tissue s ... Full text Link to item Cite

Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

Journal Article PLoS One · 2017 Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to char ... Full text Link to item Cite

Asymmetric Division of Cancer Stem Cells

Chapter · September 1, 2016 Cancer cells usually proliferate by symmetric division, producing identical copies of themselves. However, a small subset of cancer cells, mainly cancer stem cells, are capable of asymmetric cell division (ACD), producing a self-renewing daughter cell and ... Full text Cite

A recellularized human colon model identifies cancer driver genes.

Journal Article Nat Biotechnol · August 2016 Refined cancer models are needed to bridge the gaps between cell line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell-populated mucosa and ... Full text Link to item Cite

Asymmetric division: An antitumor player?

Journal Article Mol Cell Oncol · July 2016 miR-34a-mediated asymmetric cell division reins in excessive stem cell expansion during tissue regeneration in the intestine and colon. Loss of miR-34a switches asymmetric division to symmetric division and enhances stem cell proliferation. Asymmetric divi ... Full text Link to item Cite

Simultaneous optical and electrical in vivo analysis of the enteric nervous system.

Journal Article Nat Commun · June 7, 2016 The enteric nervous system (ENS) is a major division of the nervous system and vital to the gastrointestinal (GI) tract and its communication with the rest of the body. Unlike the brain and spinal cord, relatively little is known about the ENS in part beca ... Full text Link to item Cite

NOTCH Signaling Regulates Asymmetric Cell Fate of Fast- and Slow-Cycling Colon Cancer-Initiating Cells.

Journal Article Cancer Res · June 1, 2016 Colorectal cancer cells with stem-like properties, referred to as colon cancer-initiating cells (CCIC), have high tumorigenic potential. While CCIC can differentiate to promote cellular heterogeneity, it remains unclear whether CCIC within a tumor contain ... Full text Link to item Cite

The Ex Vivo Culture and Pattern Recognition Receptor Stimulation of Mouse Intestinal Organoids.

Journal Article J Vis Exp · May 18, 2016 Primary intestinal organoids are a valuable model system that has the potential to significantly impact the field of mucosal immunology. However, the complexities of the organoid growth characteristics carry significant caveats for the investigator. Specif ... Full text Link to item Cite

Notch signalling regulates asymmetric division and inter-conversion between lgr5 and bmi1 expressing intestinal stem cells.

Journal Article Sci Rep · May 16, 2016 Rapidly cycling LGR5+ intestinal stem cells (ISCs) located at the base of crypts are the primary driver of regeneration. Additionally, BMI1 expression is correlated with a slow cycling pool of ISCs located at +4 position. While previous reports have shown ... Full text Link to item Cite

A long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division.

Journal Article Elife · April 14, 2016 The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a ... Full text Open Access Link to item Cite

A real-time spike classification method based on dynamic time warping for extracellular enteric neural recording with large waveform variability.

Journal Article J Neurosci Methods · March 1, 2016 BACKGROUND: Computationally efficient spike recognition methods are required for real-time analysis of extracellular neural recordings. The enteric nervous system (ENS) is important to human health but less well-understood with few appropriate spike recogn ... Full text Link to item Cite

A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer.

Journal Article Cell Stem Cell · February 4, 2016 Featured Publication Emerging evidence suggests that microRNAs can initiate asymmetric division, but whether microRNA and protein cell fate determinants coordinate with each other remains unclear. Here, we show that miR-34a directly suppresses Numb in early-stage colon cancer ... Full text Open Access Link to item Cite

Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles.

Journal Article Biomaterials · January 2016 Circulating tumor cells (CTCs) are responsible for metastases in distant organs via hematogenous dissemination. Fundamental studies in the past decade have suggested that neutralization of CTCs in circulation could represent an effective strategy to preven ... Full text Link to item Cite

Surface Functionalized Graphene Biosensor on Sapphire for Cancer Cell Detection.

Journal Article J Nanosci Nanotechnol · January 2016 Graphene has several unique physical, optical and electrical properties such as a two-dimensional (2D) planar structure, high optical transparency and high carrier mobility at room temperature. These make graphene interesting for electrical biosensing. Usi ... Full text Link to item Cite

IRE1α is an endogenous substrate of endoplasmic-reticulum-associated degradation.

Journal Article Nat Cell Biol · December 2015 Endoplasmic reticulum (ER)-associated degradation (ERAD) represents a principle quality control mechanism to clear misfolded proteins in the ER; however, its physiological significance and the nature of endogenous ERAD substrates remain largely unexplored. ... Full text Link to item Cite

Abstract 2891: Chemokine-targeted models of human orthotopic colorectal cancer in immunocompetant mice

Conference Cancer Research · August 1, 2015 AbstractColorectal cancer (CRC) is a leading cause of cancer death. Current human CRC orthotopic xenograft models require survival surgery and do not robustly form tumors in liver, the most common site of me ... Full text Cite

Comprehensive models of human primary and metastatic colorectal tumors in immunodeficient and immunocompetent mice by chemokine targeting.

Journal Article Nat Biotechnol · June 2015 Current orthotopic xenograft models of human colorectal cancer (CRC) require surgery and do not robustly form metastases in the liver, the most common site clinically. CCR9 traffics lymphocytes to intestine and colorectum. We engineered use of the chemokin ... Full text Link to item Cite

miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β.

Journal Article Nat Commun · April 15, 2015 As patient survival drops precipitously from early-stage cancers to late-stage and metastatic cancers, microRNAs that promote relapse and metastasis can serve as prognostic and predictive markers as well as therapeutic targets for chemoprevention. Here we ... Full text Link to item Cite

Epigenetics and cancer metabolism.

Journal Article Cancer Lett · January 28, 2015 Cancer cells adapt their metabolism to support proliferation and survival. A hallmark of cancer, this alteration is characterized by dysfunctional metabolic enzymes, changes in nutrient availability, tumor microenvironment and oncogenic mutations. Metaboli ... Full text Link to item Cite

A metabolic signature of colon cancer initiating cells.

Journal Article Annu Int Conf IEEE Eng Med Biol Soc · 2014 Colon cancer initiating cells (CCICs) are more tumorigenic and metastatic than the majority of colorectal cancer (CRC) cells. CCICs have also been associated with stem cell-like properties. However, there is a lack of system-level understanding of what mec ... Full text Link to item Cite

A bio-inspired spatial patterning circuit.

Journal Article Annu Int Conf IEEE Eng Med Biol Soc · 2014 Lateral Inhibition (LI) is a widely conserved patterning mechanism in biological systems across species. Distinct from better-known Turing patterns, LI depend on cell-cell contact rather than diffusion. We built an in silico genetic circuit model to analyz ... Full text Link to item Cite

Nonamperometric CMOS sensing of intestinal action potentials

Journal Article 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2014 · January 1, 2014 A CMOS floating-gate, non-amperometric electrochemical sensor, which overcomes the invasiveness of patch-clamp and bias-setting of Ion Sensitive FET (ISFET), is proposed to detect enteric nerve system (ENS) action potentials (AP) by model-based match filte ... Cite

Post-translational regulation enables robust p53 regulation.

Journal Article BMC Syst Biol · August 30, 2013 BACKGROUND: The tumor suppressor protein p53 plays important roles in DNA damage repair, cell cycle arrest and apoptosis. Due to its critical functions, the level of p53 is tightly regulated by a negative feedback mechanism to increase its tolerance toward ... Full text Link to item Cite

A microRNA miR-34a-regulated bimodal switch targets Notch in colon cancer stem cells.

Journal Article Cell Stem Cell · May 2, 2013 Featured Publication microRNAs regulate developmental cell-fate decisions, tissue homeostasis, and oncogenesis in distinct ways relative to proteins. Here, we show that the tumor suppressor microRNA miR-34a is a cell-fate determinant in early-stage dividing colon cancer stem c ... Full text Link to item Cite

Spatial perturbation with synthetic protein scaffold reveals robustness of asymmetric cell division.

Journal Article J Biomed Sci Eng · February 2013 Asymmetric cell division is an important mechanism for creating diversity in a cellular population. Stem cells commonly perform asymmetric division to generate both a daughter stem cell for self-renewal and a more differentiated daughter cell to populate t ... Full text Link to item Cite

Chemokine 25-induced signaling suppresses colon cancer invasion and metastasis.

Journal Article J Clin Invest · September 2012 Chemotactic cytokines (chemokines) can help regulate tumor cell invasion and metastasis. Here, we show that chemokine 25 (CCL25) and its cognate receptor chemokine receptor 9 (CCR9) inhibit colorectal cancer (CRC) invasion and metastasis. We found that CCR ... Full text Link to item Cite

Using an adaptive gene network model for self-organizing multicellular behavior.

Journal Article Annu Int Conf IEEE Eng Med Biol Soc · 2012 Using the transient interleukin (IL)-2 secretion of effector T helper (T(eff)) cells as an example, we show that self-organizing multicellular behavior can be modeled and predicted by an adaptive gene network model. Incorporating an adaptation algorithm we ... Full text Link to item Cite

Adaptive models for gene networks.

Journal Article PLoS One · 2012 Biological systems are often treated as time-invariant by computational models that use fixed parameter values. In this study, we demonstrate that the behavior of the p53-MDM2 gene network in individual cells can be tracked using adaptive filtering algorit ... Full text Link to item Cite

Disturbance rejection helps modulate the P53 oscillation

Journal Article ASME 2011 Dynamic Systems and Control Conference and Bath/ASME Symposium on Fluid Power and Motion Control, DSCC 2011 · December 1, 2011 Designing a system that adequately processes the input and that rejects the effects of disturbance is a central theme in feedback control theory. In this paper, we use the concept of "disturbance rejection" to analyze the oscillatory behavior of p53, a wel ... Full text Cite

Frequency domain analysis reveals external periodic fluctuations can generate sustained p53 oscillation.

Journal Article PLoS One · 2011 p53 is a well-known tumor suppressor protein that regulates many pathways, such as ones involved in cell cycle and apoptosis. The p53 levels are known to oscillate without damping after DNA damage, which has been a focus of many recent studies. A negative ... Full text Link to item Cite

Joint DAC/IWBDA special session design and synthesis of biological circuits

Journal Article Proceedings - Design Automation Conference · January 1, 2011 With the growing complexity of synthetic biological circuits, robust and systematic methods are needed for design and test. Leveraging lessons learned from the semiconductor and design automation industries, synthetic biologists are starting to adopt compu ... Full text Cite

An essential transcription factor, SciP, enhances robustness of Caulobacter cell cycle regulation.

Journal Article Proc Natl Acad Sci U S A · November 2, 2010 A cyclical control circuit composed of four master regulators drives the Caulobacter cell cycle. We report that SciP, a helix-turn-helix transcription factor, is an essential component of this circuit. SciP is cell cycle-controlled and co-conserved with th ... Full text Link to item Cite

The class I HDAC inhibitor MGCD0103 induces cell cycle arrest and apoptosis in colon cancer initiating cells by upregulating Dickkopf-1 and non-canonical Wnt signaling.

Journal Article Oncotarget · November 2010 Colorectal cancer metastatic recurrence and chemoresistance are major causes of morbidity and mortality. Colon cancer initiating cells (CCIC) are thought to contribute to both these processes. To identify drugs with anti-CCIC activity we screened a number ... Full text Link to item Cite

Architecture and inherent robustness of a bacterial cell-cycle control system.

Journal Article Proc Natl Acad Sci U S A · August 12, 2008 A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory ... Full text Link to item Cite

Compensation for multimode fiber dispersion by adaptive optics.

Journal Article Opt Lett · November 15, 2005 Adaptive optics is used to compensate for modal dispersion in digital transmission through multimode fiber (MMF). At the transmitter, a spatial light modulator (SLM) controls the launched field pattern. An estimate of intersymbol interference (ISI) caused ... Full text Link to item Cite

Compensation of multimode fiber dispersion using adaptive optics

Conference IET Conference Publications · January 1, 2005 Adaptive optics (AO) is used to compensate modal dispersion in multimode fiber. Transmission of 10 Gb/s NRZ data through standard 50-μm fibers up to 11.1 km long is demonstrated. ... Full text Cite