The Steiner Lab is interested in understanding how and why scarring and fibrosis occur in the intestine in inflammatory bowel disease (IBD). As a physician scientist with an active IBD clinic, one of the major problems our patients face is the result of intestinal stricturing and scarring. We have many good therapies for IBD, but none directly heal or reverse the fibrosis that causes these complications. This leads to complications and the need for surgery for many of our IBD patients. The ultimate goal is that this will lead to novel therapies using these discoveries.
To achieve these goals, we focus on studying the cellular and molecular mechanisms of intestinal fibrosis and inflammation in IBD. Our work leverages many exciting techniques including human-tissue based model systems of intestinal disease and next generation sequencing techniques. To create physiologically relevant models of human disease, we utilize human intestinal organoids (HIO), enteroid, and colonoid models, as well as more traditional two-dimensional cell culture models. We have made discoveries involving several different cellular pathways that are potentially targetable as therapies for fibrosis in IBD. Our work has also led to the characterization of the “TNF delta” mouse model of IBD as also being a viable animal model of intestinal fibrosis. Ongoing research is focused on leveraging this and other models of intestinal inflammation and fibrosis to uncover the ways that the intestinal epithelium and stroma respond to the luminal microenvironment and also signal immune pathways to understand the pathophysiology of intestinal fibrosis and inflammation.
We also have a strong and active interest in the study of mucosal inflammation, and the role of the immune system and other organ systems as in the context of intestinal inflammation. These endeavors have spanned topics ranging from examining neutrophil-mediated chlorination of tight junctions, to hepatic periportal inflammation in the setting of intestinal inflammation models, to development of new models of intestinal inflammation.
Below is a select list of publications highlighting these endeavors:
Steiner CA, Rodansky ES, Johnson LA, Berinstein JA, Cushing KC, Huang S, Spence JR, Higgins PDR. AXL is a Potential Target for the Treatment of Intestinal Fibrosis. Inflammatory Bowel Diseases. 2020 July 17. https://doi.org/10.1093/ibd/izaa169 PMID: 32676663
Steiner CA, Koch SD, Evanoff T, Welch N, Kostelecky R, Callahan R, Murphy EM, Nguyen TT, Hall CHT, Lu S, de Zoeten EF, Weiser-Evans MCM, Cartwright IM, Colgan SP. The TNFΔARE Mouse as a Model of Intestinal Fibrosis. Am J Pathol. 2023 Aug;193(8):1013-1028. doi: 10.1016/j.ajpath.2023.04.009. Epub 2023 May 9. PMID: 37169343; PMCID: PMC10433691.
Steiner CA, Cartwright IM, Taylor CT, Colgan SP. Hypoxia-inducible factor as a bridge between healthy barrier function, wound healing, and fibrosis. Am J Physiol Cell Physiol. 2022 Sep 1;323(3):C866-C878. doi: 10.1152/ajpcell.00227.2022. Epub 2022 Aug 1. PMID: 35912990.
Steiner CA, Berinstein JA, Louissaint J, Higgins PDR, Spence JR, Shannon C, Lu C, Stidham RW, Fletcher JG, Bruining DH, Feagan BG, Jairath V, Baker ME, Bettenworth D, Rieder F; Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium. Biomarkers for the Prediction and Diagnosis of Fibrostenosing Crohn's Disease: A Systematic Review. Clin Gastroenterol Hepatol. 2022 Apr;20(4):817-846.e10. doi: 10.1016/j.cgh.2021.05.054. Epub 2021 Jun 2. PMID: 34089850; PMCID: PMC8636551.
Yu Q, Kilik U, Secchia S, Adam L, Tsai YH, Fauci C, Janssens J, Childs CJ, Walton KD, López-Sandoval R, Wu A, Almató Bellavista M, Huang S, Steiner CA, Throm Y, Boyle MJ, He Z, Beumer J, Treutlein B, Lowe CB, Spence JR, Camp JG. Recent evolution of the developing human intestine affects metabolic and barrier functions. Science. 2025 Aug 21;389(6762):eadr8628. doi: 10.1126/science.adr8628. Epub 2025 Aug 21. PubMed PMID: 40674448; PubMed Central PMCID: PMC12495891.
Saeedi BJ, Carr HE, Higgins PDR, Steiner CA. AXL: A novel therapeutic target in IBD. Adv Pharmacol. 2024;101:141-157. doi: 10.1016/bs.apha.2024.10.009. Epub 2024 Oct 22. Review. PubMed PMID: 39521598.
Johnson LA, Rodansky ES, Tran A, Collins SG, Eaton KA, Malamet B, Steiner CA, Huang S, Spence JR, Higgins PDR. Effect of ABT-263 on Intestinal Fibrosis in Human Myofibroblasts, Human Intestinal Organoids, and the Mouse Salmonella typhimurium Model. Inflamm Bowel Dis. 2022 Feb 1;28(2):161-175. doi: 10.1093/ibd/izab166. PMID: 34302470; PMCID: PMC9017142.
Chilukuri A, Kim M, Mitra T, Gubatan JM, Urrete J, Saxon LD, Ablack A, Mikulski Z, Dobaczewska K, Shen Z, Keir M, Yi T, Kaur P, Oliveira P, Murillo-Saich J, Chang EY, Steiner CA, Jedlicka P, Guma M, Rivera-Nieves J. A Similar Mutation in the AAUU-Rich Elements of the Mouse TNF Gene Results in a Distinct Ileocolitic Phenotype: A New Strain of TNF-Overexpressing Mice. Inflamm Bowel Dis. 2025 Apr 10;31(4):1067-1081. doi: 10.1093/ibd/izae307. PMID: 39756463; PMCID: PMC11985683.
Shearn CT, Anderson AL, Devereaux MW, Koch SD, Larsen LD, Spencer LA, Orlicky DJ, Colgan SP, Steiner CA, Sokol RJ. Overexpression of TNFα in TNF∆ARE+/- mice increases hepatic periportal inflammation and alters bile acid signaling in mice. Hepatol Commun. 2024 Nov 25;8(12):e0589. doi: 10.1097/HC9.0000000000000589. PMID: 39585296; PMCID: PMC11596574.
Cartwright IM, Zhou L, Koch SD, Welch N, Zakharov D, Callahan R, Steiner CA, Gerich ME, Onyiah JC, Colgan SP. Chlorination of epithelial tight junction proteins by neutrophil myeloperoxidase promotes barrier dysfunction and mucosal inflammation. JCI Insight. 2024 Jun 11;9(14):e178525. doi: 10.1172/jci.insight.178525. PMID: 39133648; PMCID: PMC11383587.
Cartwright IM, Dowdell AS, Hanson C, Kostelecky RE, Welch N, Steiner CA, Colgan SP. Contact-dependent, polarized acidification response during neutrophil-epithelial interactions. J Leukoc Biol. 2022 Dec;112(6):1543-1553. doi: 10.1002/JLB.3MA0422-742R. Epub 2022 Jun 8. PMID: 35674095; PMCID: PMC9701153.
Steiner CA, Higgins P.R. (2018) Anti-Fibrotic Therapies from Other Organs: What the Gut Can Learn from the Liver, Skin, Lung and Heart. In: Rieder F. (eds) Fibrostenotic Inflammatory Bowel Disease. Springer, Cham
Steiner CA, Whitfield EP, Adler J, Higgins PDR (2017) Anti-TNF Biologic Therapies Other than Infliximab. In: Mamula P., Grossman A., Baldassano R., Kelsen J., Markowitz J. (eds) Pediatric Inflammatory Bowel Disease. Springer, Cham
Berinstein JA, Steiner CA, Regal RE, Allen JI, Kinnucan JAR, Stidham RW, Waljee AK, Bishu S, Aldrich LB, Higgins PDR. Efficacy of Induction Therapy With High-Intensity Tofacitinib in 4 Patients With Acute Severe Ulcerative Colitis. Clinical Gastroenterology and Hepatology. 2019 Apr;17(5):988-990. PMID: 30458248
Callahan RC, Curry JC, Bhagavatula G, Staley AW, Schaefer RE, Minhajuddin F, Zhou L, Neuhart RM, Atif SM, Orlicky DJ, Cartwright IM, Gerich ME, Steiner CA, Theiss AL, Hall CH, Colgan SP, Onyiah JC. Epithelial HO-1 regulates iron availability and promotes colonic tumorigenesis in a context-dependent manner. JCI Insight. 2025 Dec 17;. doi: 10.1172/jci.insight.181032. [Epub ahead of print] PubMed PMID: 41410530
Ye Le, PhD  |
I am currently working on two projects focused on fibrostenosis in Crohn’s disease. The first investigates how extracellular vesicles (EVs) isolated from patient-derived intestinal enteroids influence fibroblast activation. These EVs are used to treat primary intestinal fibroblasts derived from Crohn’s disease patients to assess their effects on fibrogenic signaling and cellular behavior. The second project examines the GAS6/AXL signaling pathway and its role in epithelial–stromal communication and fibrotic remodeling. Together, these studies aim to define novel mechanisms driving intestinal fibrosis and to identify potential therapeutic targets to prevent or reverse fibrostenotic complications in Crohn’s disease.
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Katherine Hullin
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I am a medical student interested in a career as a physician scientist. In the Steiner Lab I am studying the role of a tyrosine kinase inhibitor called Axl in intestinal fibrosis. I did my undergrad at the University of Wisconsin-Madison in Genetics and Anthropology, and I spent my gap years at the NIH studying the genetic underpinnings of pancreatic cancer. I’m interested in internal medicine/gastroenterology, and surgery and hope to continue doing research as a physician. |
Calen A. Steiner MD MS
Assistant Professor of Medicine
GI and Liver Innate Immune Programs | UC Crohn’s & Colitis Center
Division of Gastroenterology & Hepatology
University of Colorado Hospital | Anschutz Medical Campus
12700 E. 19th Avenue,
MS B146, Lab P15-10450C
Aurora, CO 80045