Mark Donowitz

Flagellar regulation in enterotoxigenic E. coli modulates innate immune activation

Pauline T. Ikpa, Amanda Nengel, James B. Kaper, Mark Donowitz et autres

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) remains a leading cause of diarrheal disease in low- and middle-income countries, yet vaccine efforts have struggled to achieve broad and durable protection. To better understand early steps in host-pathogen interactions, we utilized human stem cell-derived jejunal …

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Building and regenerating intestines by manipulating intestinal stem cells

Calvin J. Kuo, Sarah Blutt, Mark Donowitz, Mary K. Estes et autres

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Aldosterone suppresses Na + /H + exchanger-3 expression through miR-204-5P-mediated posttranscriptional regulation in distal colon

Karthikeyan Narayanan, Kumaran M. Rajendran, Joshua Cornman‐Homonoff, Mark Donowitz et autres

This study identifies a previously unrecognized aldosterone-microRNA signaling mechanism regulating colonic Na + absorption. We demonstrate that aldosterone induces miR-204-5P, which directly targets the NHE3 3′-untranslated region and suppresses NHE3 expression and transport activity in distal colonic epithelium. These findings reveal a …

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In Memoriam: Henry J. Binder, MD (1936–2025)

Mark Donowitz, Michael H. Nathanson, Loren Laine, Vazhaikkurichi M. Rajendran et autres

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Farnesoid X Receptor Activation Upregulates Expression of the Transcription Elongation Factor, TCEA2, in Intestinal Epithelial Cells

Jessica Smyth, Jennifer Foulke-Abel, Ruxian Lin, Mark Donowitz et autres

BACKGROUND: Oxidative DNA damage occurs during mucosal inflammation, with such lesions stalling RNA polymerase II and impairing transcription fidelity, thereby driving genomic instability, a hallmark of cancer. TCEA2 (TFIIS) is a transcription elongation factor that rescues stalled polymerases by stimulating transcript cleavage, …

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A model for Crohn’s disease post-ileal resection fibrosis development using human ileal enteroids and myofibroblasts

Jun Hwan Yoo, Yoon Jeong Choi, Iryna V. Pinchuk, Don Powell et autres

Background Fibrosis and inflammation frequently emerge soon after ileal resection for strictures in Crohn’s disease (CD). Objective This study examined the profibrotic and proinflammatory effects of conditioned media from TNF and IFN-γ (T+I)-exposed healthy and inactive CD ileal enteroids (CDiE) on subepithelial …

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Nherf2 is a major determinant of bile acid pool dynamics and contributes to regulation of Western diet-induced obesity

Dachuan Dong, Wen‐Jun Shen, Stefanie Bittner, Jia Chen et autres

Nherf2 −/− but not Nherf1 −/− mice demonstrate a resistance to diet-induced obesity. Notably, male Nherf2 −/− mice exhibit impaired glucose tolerance and insulin responsiveness, yet neither sex shows further worsening with diet challenge. In addition, elevated hepatic Cyp7a1 levels were observed …

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Differential Regulation of NHE3 Expression in Type 1 and Type 2 Diabetic Intestine: Impaired Endosomal Regulation of NHE3 Expression in Type 1 Diabetes

Varsha Singh, Ruxian Lin, Laxmi Sunuwar, Jianbo Yang et autres

Abstract Chronic diarrhea is a frequent gastrointestinal complication in both type 1 (T1D) and type 2 diabetes (T2D), though the underlying mechanisms differ: T1D is linked to autonomic neuropathy and disrupted transporter regulation, while T2D is often linked to medications and intestinal …

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Differential regulation of NHE3 expression in type 1 and type 2 diabetic intestine: impaired endosomal regulation of NHE3 expression in type 1 diabetes

Varsha Singh, Ruxian Lin, Laxmi Sunuwar, Jianbo Yang et autres

This study identifies distinct mechanisms of impaired sodium absorption contributing to diabetic diarrhea in type 1 and type 2 diabetes. We identify SNX17 as a novel regulator of NHE3 in the small intestine, showing that SNX17 loss in T1D contributes to posttranslational …

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INSL5 as a newly recognised potential contributor to diarrhoea pathogenesis: more questions than answers

Mark Donowitz, Varsha Singh

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IRBIT and LIMA1 associate with and are necessary for epithelial cell SLC26A3 (DRA) stimulation by cAMP/ATP

Rafiquel Sarker, Tatiana B. Boronia, Robert N. Cole, Varsha Singh et autres

Insights into acute DRA regulation relevant to secretory diarrhea studied synergistic cAMP and Ca 2+ -induced DRA stimulation. DRA was phosphorylated under baseline conditions, which decreased with acute stimulation. Acute stimulation, but not basal activity, required the presence of both IRBIT and …

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Partially differentiated ileal and distal-colonic human F508del-cystic fibrosis-enteroids secrete fluid in response to forskolin and linaclotide

Rong Yan, Zixin Zhang, Hugo R. de Jonge, Ruxian Lin et autres

ileal and distal colonic/rectal enteroids as a model and the Forskolin Induced Swelling Assay (FIS), we compared CFTR mediated fluid secretion in human enterocytes across the crypt-villus axis. CFTR expression and FIS decreased as enterocytes differentiated from crypt to become partially differentiated …

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