Scholars@Duke
Jatin Roper

Jatin Roper

Assistant Professor of Medicine
Medicine, Gastroenterology
jatin.roper@duke.edu
DUMC 103862, Durham, NC 27710
905 S. LaSalle Street, GSRB-1, Room 1033, Durham, NC 27710

Selected Publications

Asparagine synthetase and G-protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer.

Journal Article Int J Cancer · January 1, 2025 Survival differences exist in colorectal cancer (CRC) patients by sex and disease stage. However, the potential molecular mechanism(s) are not well understood. Here we show that asparagine synthetase (ASNS) and G protein-coupled estrogen receptor-1 (GPER1) ... Full text Link to item Cite

Estrogen signaling suppresses tumor-associated tissue eosinophilia to promote breast tumor growth.

Journal Article Sci Adv · September 27, 2024 Estrogens regulate eosinophilia in asthma and other inflammatory diseases. Further, peripheral eosinophilia and tumor-associated tissue eosinophilia (TATE) predicts a better response to immune checkpoint blockade (ICB) in breast cancer. However, how and if ... Full text Link to item Cite

Deep learning classification of ex vivo human colon tissues using spectroscopic optical coherence tomography.

Journal Article J Biophotonics · September 2024 Screening for colorectal cancer (CRC) with colonoscopy has improved patient outcomes; however, it remains the third leading cause of cancer-related mortality, novel strategies to improve screening are needed. Here, we propose an optical biopsy technique ba ... Full text Link to item Cite

Short-term post-fast refeeding enhances intestinal stemness via polyamines.

Journal Article Nature · September 2024 For over a century, fasting regimens have improved health, lifespan and tissue regeneration in diverse organisms, including humans1-6. However, how fasting and post-fast refeeding affect adult stem cells and tumour formation has yet to be explored in depth ... Full text Link to item Cite

Multi-omic analysis reveals metabolic pathways that characterize right-sided colon cancer liver metastasis.

Journal Article Cancer Lett · October 10, 2023 There are well demonstrated differences in tumor cell metabolism between right sided (RCC) and left sided (LCC) colon cancer, which could underlie the robust differences observed in their clinical behavior, particularly in metastatic disease. As such, we u ... Full text Link to item Cite

Deep learning classification of ex vivo human colon tissues using spectroscopic OCT.

Journal Article bioRxiv · September 6, 2023 Screening programs for colorectal cancer (CRC) have had a profound impact on the morbidity and mortality of this disease by detecting and removing early cancers and precancerous adenomas with colonoscopy. However, CRC continues to be the third leading caus ... Full text Link to item Cite

Ablative radiotherapy improves survival but does not cure autochthonous mouse models of prostate and colorectal cancer.

Journal Article Commun Med (Lond) · August 9, 2023 BACKGROUND: Genetically engineered mouse models (GEMMs) of cancer are powerful tools to study mechanisms of disease progression and therapy response, yet little is known about how these models respond to multimodality therapy used in patients. Radiation th ... Full text Link to item Cite

Mutant APC reshapes Wnt signaling plasma membrane nanodomains by altering cholesterol levels via oncogenic β-catenin.

Journal Article Nat Commun · July 19, 2023 Although the role of the Wnt pathway in colon carcinogenesis has been described previously, it has been recently demonstrated that Wnt signaling originates from highly dynamic nano-assemblies at the plasma membrane. However, little is known regarding the r ... Full text Link to item Cite

A LGR5 reporter pig model closely resembles human intestine for improved study of stem cells in disease.

Journal Article FASEB journal : official publication of the Federation of American Societies for Experimental Biology · June 2023 Intestinal epithelial stem cells (ISCs) are responsible for intestinal epithelial barrier renewal; thereby, ISCs play a critical role in intestinal pathophysiology research. While transgenic ISC reporter mice are available, advanced translational studies l ... Full text Cite

Metabolism and Colorectal Cancer.

Journal Article Annual review of pathology · January 2023 Reprogrammed metabolism is a hallmark of colorectal cancer (CRC). CRC cells are geared toward rapid proliferation, requiring nutrients and the removal of cellular waste in nutrient-poor environments. Intestinal stem cells (ISCs), the primary cell of origin ... Full text Cite

Colorectal Cancer Immunotherapy: State of the Art and Future Directions.

Journal Article Gastro Hep Adv · 2023 Cancer immunotherapy has become an indispensable mode of treatment for a multitude of solid tumor cancers. Colorectal cancer (CRC) has been one of the many cancer types to benefit from immunotherapy, especially in advanced disease where standard treatment ... Full text Link to item Cite

The intestine is a major contributor to circulating succinate in mice.

Journal Article FASEB J · October 2022 The tricarboxylic acid (TCA) cycle is the epicenter of cellular aerobic metabolism. TCA cycle intermediates facilitate energy production and provide anabolic precursors, but also function as intra- and extracellular metabolic signals regulating pleiotropic ... Full text Link to item Cite

Weight Loss and/or Sulindac Mitigate Obesity-associated Transcriptome, Microbiome, and Protumor Effects in a Murine Model of Colon Cancer.

Journal Article Cancer Prev Res (Phila) · August 1, 2022 UNLABELLED: Obesity is associated with an increased risk of colon cancer. Our current study examines whether weight loss and/or treatment with the NSAID sulindac suppresses the protumor effects of obesity in a mouse model of colon cancer. Azoxymethane-trea ... Full text Link to item Cite

Spectroscopic optical coherence tomography for classification of colorectal cancer in a mouse model.

Journal Article J Biophotonics · July 2022 Noninvasive diagnosis of the malignant potential of colon polyps can improve prevention of colorectal cancer without the need for time-consuming and expensive biopsies. This study examines the use of spectroscopic optical coherence tomography (OCT) to clas ... Full text Link to item Cite

Cause, Epidemiology, and Histology of Polyps and Pathways to Colorectal Cancer.

Journal Article Gastrointest Endosc Clin N Am · April 2022 Colorectal cancer is the second leading cause of cancer-associated mortality, with a lifetime risk of approximately 4% to 5%. Colorectal cancer develops from the sequential acquisition of defined genetic mutations in the colonic epithelium. Tumorigenesis f ... Full text Link to item Cite

Combined Supplementation with Vitamin B-6 and Curcumin is Superior to Either Agent Alone in Suppressing Obesity-Promoted Colorectal Tumorigenesis in Mice.

Journal Article J Nutr · December 3, 2021 BACKGROUND: Obesity increases the colorectal cancer risk, in part by elevating colonic proinflammatory cytokines. Curcumin (CUR) and supplemental vitamin B-6 each suppress colonic inflammation. OBJECTIVES: We examined whether the combination of CUR and vit ... Full text Link to item Cite

Dietary suppression of MHC class II expression in intestinal epithelial cells enhances intestinal tumorigenesis.

Journal Article Cell Stem Cell · November 4, 2021 Little is known about how interactions of diet, intestinal stem cells (ISCs), and immune cells affect early-stage intestinal tumorigenesis. We show that a high-fat diet (HFD) reduces the expression of the major histocompatibility complex class II (MHC clas ... Full text Link to item Cite

Epithelial Regeneration After Doxorubicin Arises Primarily From Early Progeny of Active Intestinal Stem Cells.

Journal Article Cell Mol Gastroenterol Hepatol · 2021 BACKGROUND & AIMS: aISCs (aISCs) are sensitive to acute insults including chemotherapy and irradiation. Regeneration after aISC depletion has primarily been explored in irradiation (IR). However, the cellular origin of epithelial regeneration after doxorub ... Full text Link to item Cite

Regenerative Reprogramming of the Intestinal Stem Cell State via Hippo Signaling Suppresses Metastatic Colorectal Cancer.

Journal Article Cell Stem Cell · October 1, 2020 Although the Hippo transcriptional coactivator YAP is considered oncogenic in many tissues, its roles in intestinal homeostasis and colorectal cancer (CRC) remain controversial. Here, we demonstrate that the Hippo kinases LATS1/2 and MST1/2, which inhibit ... Full text Link to item Cite

Loss of aryl hydrocarbon receptor potentiates FoxM1 signaling to enhance self-renewal of colonic stem and progenitor cells.

Journal Article EMBO J · October 1, 2020 The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that senses xenobiotics, diet, and gut microbial-derived metabolites, is increasingly recognized as a key regulator of intestinal biology. However, its effects on the function of ... Full text Link to item Cite

Allosteric inhibitor of β-catenin selectively targets oncogenic Wnt signaling in colon cancer.

Journal Article Sci Rep · May 15, 2020 Abnormal regulation of β-catenin initiates an oncogenic program that serves as a main driver of many cancers. Albeit challenging, β-catenin is an attractive drug target due to its role in maintenance of cancer stem cells and potential to eliminate cancer r ... Full text Link to item Cite

Agrin in the Muscularis Mucosa Serves as a Biomarker Distinguishing Hyperplastic Polyps from Sessile Serrated Lesions.

Journal Article Clin Cancer Res · March 15, 2020 PURPOSE: Sessile serrated lesions (SSL) are precursors to colon carcinoma, and their distinction from other polyps, in particular hyperplastic polyps (HP), presents significant diagnostic challenges. We evaluated expression patterns in colonic polyps of pr ... Full text Link to item Cite

An Insoluble Mystery: Fiber and Diverticulitis.

Journal Article Gastroenterology · March 2020 Full text Link to item Cite

Epithelial NOTCH Signaling Rewires the Tumor Microenvironment of Colorectal Cancer to Drive Poor-Prognosis Subtypes and Metastasis.

Journal Article Cancer Cell · September 16, 2019 The metastatic process of colorectal cancer (CRC) is not fully understood and effective therapies are lacking. We show that activation of NOTCH1 signaling in the murine intestinal epithelium leads to highly penetrant metastasis (100% metastasis; with >80% ... Full text Link to item Cite

Gut organoids: mini-tissues in culture to study intestinal physiology and disease.

Journal Article Am J Physiol Cell Physiol · September 1, 2019 In vitro, cell cultures are essential tools in the study of intestinal function and disease. For the past few decades, monolayer cellular cultures, such as cancer cell lines or immortalized cell lines, have been widely applied in gastrointestinal research. ... Full text Link to item Cite

The combination of TPL2 knockdown and TNFα causes synthetic lethality via caspase-8 activation in human carcinoma cell lines.

Journal Article Proc Natl Acad Sci U S A · July 9, 2019 Most normal and tumor cells are protected from tumor necrosis factor α (TNFα)-induced apoptosis. Here, we identify the MAP3 kinase tumor progression locus-2 (TPL2) as a player contributing to the protection of a subset of tumor cell lines. The combination ... Full text Link to item Cite

Notum produced by Paneth cells attenuates regeneration of aged intestinal epithelium.

Journal Article Nature · July 2019 A decline in stem cell function impairs tissue regeneration during ageing, but the role of the stem-cell-supporting niche in ageing is not well understood. The small intestine is maintained by actively cycling intestinal stem cells that are regulated by th ... Full text Link to item Cite

Breakthrough Moments: Genome Editing and Organoids.

Journal Article Cell Stem Cell · June 6, 2019 Six years ago, Schwank et al. (2013) adapted CRISPR-Cas9 and organoid technology to repair genetic diseases in patient-derived tissues. We shine a spotlight on how this work has inspired the development of tools to study and correct genetic diseases in exp ... Full text Link to item Cite

Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis.

Journal Article Gut · April 2019 OBJECTIVE: Serrated colorectal cancer (CRC) accounts for approximately 25% of cases and includes tumours that are among the most treatment resistant and with worst outcomes. This CRC subtype is associated with activating mutations in the mitogen-activated ... Full text Link to item Cite

WRN helicase is a synthetic lethal target in microsatellite unstable cancers.

Journal Article Nature · April 2019 Synthetic lethality-an interaction between two genetic events through which the co-occurrence of these two genetic events leads to cell death, but each event alone does not-can be exploited for cancer therapeutics1. DNA repair processes represent attractiv ... Full text Link to item Cite

High-fructose corn syrup enhances intestinal tumor growth in mice.

Journal Article Science · March 22, 2019 Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated with obesity and with an increased risk of colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. We investigated the effects of dail ... Full text Link to item Cite

Ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and topical applications

Journal Article Materials Today · March 1, 2019 Cellulose acetate (CA), viscose, or artificial silk are biocompatible human-benign derivatives of cellulose, one of the most abundant biopolymers on earth. While various optical materials have been developed from CA, optical CA nanomaterials are nonexisten ... Full text Cite

Data on ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and topical applications

Journal Article Data in Brief · February 1, 2019 Characterization data of fluorescent nanoparticles made of cellulose acetate (CA-dots) are shown. The data in this article accompanies the research article “Ultrabright fluorescent cellulose acetate nanoparticles for imaging tumors through systemic and top ... Full text Cite

Parabacteroides distasonis attenuates toll-like receptor 4 signaling and Akt activation and blocks colon tumor formation in high-fat diet-fed azoxymethane-treated mice.

Journal Article Int J Cancer · October 1, 2018 Gut dysbiosis may play an etiological role in colorectal tumorigenesis. We previously observed that the abundance of Parabacteroides distasonis (Pd) in stool was inversely associated with intestinal tumor burden and IL-1β concentrations in mice. Here, we a ... Full text Link to item Cite

Author Correction: High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.

Journal Article Nature · August 2018 In Fig. 4e of this Article, the labels for 'Control' and 'HFD' were reversed ('Control' should have been labelled blue rather than purple, and 'HFD' should have been labelled purple rather than blue). Similarly, in Fig. 4f of this Article, the labels for ' ... Full text Link to item Cite

Colonoscopy-based colorectal cancer modeling in mice with CRISPR-Cas9 genome editing and organoid transplantation.

Journal Article Nat Protoc · February 2018 Most genetically engineered mouse models (GEMMs) of colorectal cancer are limited by tumor formation in the small intestine, a high tumor burden that limits metastasis, and the need to generate and cross mutant mice. Cell line or organoid transplantation m ... Full text Link to item Cite

PKM2 is not required for colon cancer initiated by APC loss

Journal Article Cancer & Metabolism · December 2017 Full text Cite

In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis.

Journal Article Nat Biotechnol · June 2017 In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing an ... Full text Link to item Cite

Metabolic Teamwork in the Stem Cell Niche.

Journal Article Cell Metab · May 2, 2017 Nearby cells can support stem cell differentiation, but the metabolic activities in stem cell niches are unknown. A recent study (Rodríguez-Colman et al., 2017) reveals a metabolic partnership in the intestinal stem cell niche: glycolysis in niche Paneth c ... Full text Link to item Cite

The Cancer Stem Cell Niche

Chapter · April 14, 2017 Tumors are heterogeneous and composed of cells with different phenotypic, genetic, and functional features. In some tumors, a subset of cells can recapitulate the primary tumor upon serial transplantation into immunodeficient mice. These rare highly tumori ... Full text Cite

Bariatric Surgery Prior to Index Screening Colonoscopy Is Associated With a Decreased Rate of Colorectal Adenomas in Obese Individuals

Journal Article Clinical and Translational Gastroenterology · February 9, 2017 Objectives: Obesity is an important risk factor for the development of colorectal cancer (CRC). Although the impact of bariatric surgery on CRC is conflicting, its impact on precursor lesions is unknown. The aim of this study was to determine whether baria ... Full text Cite

High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.

Journal Article Nature · March 3, 2016 Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we show that high-fat diet (HFD)-induced obesity augments the numbers and function of Lgr5(+) intestinal stem cells of the mammalian intestine. Mechanistica ... Full text Link to item Cite

Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH.

Journal Article Science · December 11, 2015 More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations and are often refractory to approved targeted therapies. We found that cultured human CRC cells harboring KRAS or BRAF mutations are selectively killed when exposed to hi ... Full text Link to item Cite

Colorectal cancer models for novel drug discovery.

Journal Article Expert Opin Drug Discov · 2015 INTRODUCTION: Despite increased screening rates and advances in targeted therapy, colorectal cancer (CRC) remains the third leading cause of cancer-related mortality. CRC models that recapitulate key features of human disease are essential to the developme ... Full text Link to item Cite

Resistance to dual blockade of the kinases PI3K and mTOR in KRAS-mutant colorectal cancer models results in combined sensitivity to inhibition of the receptor tyrosine kinase EGFR.

Journal Article Sci Signal · November 11, 2014 Targeted blockade of aberrantly activated signaling pathways is an attractive therapeutic strategy for solid tumors, but drug resistance is common. KRAS is a frequently mutated gene in human cancer but remains a challenging clinical target. Inhibitors agai ... Full text Link to item Cite

Co-occurrence of idiopathic granulomatous hepatitis and primary biliary cirrhosis.

Journal Article Dig Dis Sci · November 2014 BACKGROUND: PBC is an autoimmune disease affecting the bile ducts. Granulomas can be found in portal triads in 45 % of patients with PBC. Idiopathic granulomatous hepatitis is a rare disease of unknown cause which is characterized by recurrent fevers, swea ... Full text Link to item Cite

Overview of genetically engineered mouse models of colorectal carcinoma to enable translational biology and drug development.

Journal Article Curr Protoc Pharmacol · June 16, 2014 Preclinical models for colorectal cancer (CRC) are critical for translational biology and drug development studies to characterize and treat this condition. Mouse models of human cancer are particularly popular because of their relatively low cost, short l ... Full text Link to item Cite

Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer.

Journal Article Cancer Lett · June 1, 2014 PI3K inhibition in combination with other agents has not been studied in the context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3 ... Full text Link to item Cite

Cross-species analysis of genetically engineered mouse models of MAPK-driven colorectal cancer identifies hallmarks of the human disease.

Journal Article Dis Model Mech · June 2014 Effective treatment options for advanced colorectal cancer (CRC) are limited, survival rates are poor and this disease continues to be a leading cause of cancer-related deaths worldwide. Despite being a highly heterogeneous disease, a large subset of indiv ... Full text Link to item Cite

mTOR inhibition specifically sensitizes colorectal cancers with KRAS or BRAF mutations to BCL-2/BCL-XL inhibition by suppressing MCL-1.

Journal Article Cancer Discov · January 2014 Colorectal cancers harboring KRAS or BRAF mutations are refractory to current targeted therapies. Using data from a high-throughput drug screen, we have developed a novel therapeutic strategy that targets the apoptotic machinery using the BCL-2 family inhi ... Full text Link to item Cite

Abstract C263: mTOR inhibition specifically sensitizes colorectal cancers with KRAS or BRAF mutations to BCL-2/BCL-XL inhibition by suppressing MCL-1.

Conference Molecular Cancer Therapeutics · November 1, 2013 AbstractColorectal cancers (CRCs) harboring KRAS or BRAF mutations are refractory to current targeted therapies. Using data from a high-throughput drug screen, we have developed a novel therapeutic strategy ... Full text Cite

Development of a colon cancer GEMM-derived orthotopic transplant model for drug discovery and validation.

Journal Article Clin Cancer Res · June 1, 2013 PURPOSE: Effective therapies for KRAS-mutant colorectal cancer (CRC) are a critical unmet clinical need. Previously, we described genetically engineered mouse models (GEMM) for sporadic Kras-mutant and non-mutant CRC suitable for preclinical evaluation of ... Full text Link to item Cite

Molecular mechanisms of colorectal carcinogenesis

Chapter · June 1, 2013 Colorectal cancer (CRC) presents in three major forms: inherited, sporadic, and familial. Although the mechanisms underlying familial CRC are poorly understood, a large body of evidence suggests that inherited and sporadic CRC are caused by sequential gene ... Full text Cite

Concomitant BRAF and PI3K/mTOR blockade is required for effective treatment of BRAF(V600E) colorectal cancer.

Journal Article Clin Cancer Res · May 15, 2013 PURPOSE: BRAF(V600E) mutations are associated with poor clinical prognosis in colorectal cancer (CRC). Although selective BRAF inhibitors are effective for treatment of melanoma, comparable efforts in CRC have been disappointing. Here, we investigated pote ... Full text Link to item Cite

Priceless GEMMs: genetically engineered mouse models for colorectal cancer drug development.

Journal Article Trends Pharmacol Sci · August 2012 To establish effective drug development for colorectal cancer (CRC), preclinical models that are robust surrogates for human disease are crucial. Mouse models are an attractive platform because of their relatively low cost, short life span, and ease of use ... Full text Link to item Cite

The effect of H. pylori eradication on meal-associated changes in plasma ghrelin and leptin.

Journal Article BMC Gastroenterol · April 14, 2011 BACKGROUND: Appetite and energy expenditure are regulated in part by ghrelin and leptin produced in the gastric mucosa, which may be modified by H. pylori colonization. We prospectively evaluated the effect of H. pylori eradication on meal-associated chang ... Full text Link to item Cite

The dual PI3K/mTOR inhibitor NVP-BEZ235 induces tumor regression in a genetically engineered mouse model of PIK3CA wild-type colorectal cancer.

Journal Article PLoS One · 2011 PURPOSE: To examine the in vitro and in vivo efficacy of the dual PI3K/mTOR inhibitor NVP-BEZ235 in treatment of PIK3CA wild-type colorectal cancer (CRC). EXPERIMENTAL DESIGN: PIK3CA mutant and wild-type human CRC cell lines were treated in vitro with NVP- ... Full text Link to item Cite

The effect of laparoscopic gastric banding surgery on plasma levels of appetite-control, insulinotropic, and digestive hormones.

Journal Article Obes Surg · September 2008 BACKGROUND: We hypothesized that laparoscopic adjustable gastric banding (LAGB) reduces weight and modulates ghrelin production, but largely spares gastrointestinal endocrine function. To examine this hypothesis, we determined plasma concentrations of appe ... Full text Link to item Cite

Leptin and ghrelin in relation to Helicobacter pylori status in adult males.

Journal Article J Clin Endocrinol Metab · June 2008 CONTEXT: Leptin and ghrelin, hormones involved in human energy homeostasis, are both produced in the stomach. OBJECTIVE: We sought to determine whether the presence of Helicobacter pylori affects gastric and systemic levels of leptin and ghrelin. DESIGN, S ... Full text Link to item Cite

The association of gastric leptin with oesophageal inflammation and metaplasia.

Journal Article Gut · January 2008 BACKGROUND: Gastro-oesophageal reflux disease complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence oesophageal mucosal homeostasis. AIMS: To determine whether leptin recepto ... Full text Link to item Cite

Helicobacter pylori stimulates gastric epithelial cell MMP-1 secretion via CagA-dependent and -independent ERK activation.

Journal Article J Biol Chem · June 29, 2007 Because the mechanisms of Helicobacter pylori-induced gastric injury are incompletely understood, we examined the hypothesis that H. pylori induces matrix metalloproteinase-1 (MMP-1) secretion, with potential to disrupt gastric stroma. We further tested th ... Full text Link to item Cite