
Michele A. Battle, PhD
Professor
Locations
- Cell Biology, Neurobiology & Anatomy
Contact Information
Education
BS, University of Scranton, PA, 1996
Biography
Research Interests
Battle Lab - 2022 CMGH Journal Cover

Examining Gastrointestinal Diseases Through Developmental Biology
Description of Research
The Battle lab examines digestive diseases through a developmental biology lens. Reactivation of pathways used during embryonic organ development to pattern tissues and specify cell fate and function often plays a role in disease. Therefore, investigating organ development can provide a unique window into the mechanisms of human diseases. Using cutting-edge molecular and cellular biology tools in the context of animal and organoid model systems, we seek to delineate fundamental mechanisms of gastrointestinal epithelial tissue patterning, epithelial cell specification and differentiation, and epithelial tissue morphogenesis. The long-term goal is to apply the knowledge gained to gastrointestinal diseases, including short bowel syndrome, inflammatory bowel disease, metaplasia such as Barrett's esophagus, and cancer.A simple idea has guided my research approach: the unique assembly of transcription factors present in cells directs organ patterning, cell specification and differentiation, and tissue morphogenesis. Complexity arises with spatiotemporal changes in the transcription factor landscape. My laboratory primarily focuses on how GATA transcription factors, particularly GATA4 and GATA6, regulate gastrointestinal organ development and how alterations in GATA factor function contribute to GI diseases.
Overall, my laboratory has made significant contributions to our understanding of the essential transcriptional and signaling mechanisms regulating the development and function of the GI epithelium and how alterations in these mechanisms may contribute to gastrointestinal diseases, including cancer. We integrate cellular and molecular biology tools to explore fundamental cell functions in healthy and diseased tissues. We envision that the insights we provide about organ development and cell functions will be applicable long-term to identifying screening and therapeutic targets and to regenerative medicine strategies that strive to generate specific GI cell types and tissue-engineered GI organs to replace functions lost in disease or injury.
Current Projects
Examining the role of GATA4 in gastric parietal cell development and disease:
Parietal cells provide essential GI functions, producing and secreting gastric acid for digestion and to kill pathogens. These cells also synthesize growth factors that influence parietal cells themselves and other gastric cell types. Parietal cell dysfunction underlies a range of human diseases associated with a high socioeconomic burden, including chronic gastritis, drug-related peptic ulcer disease, Helicobacter pylori-related peptic ulcer disease, H. pylori-associated gastritis, metaplasia, and cancer. Parietal cell loss is a crucial pathological step in gastric cancer. However, the mechanisms through which parietal cells are specified and maintained and how loss of parietal cells contributes to gastric disease are poorly defined. The idea that GATA family transcription factors regulate parietal cell function was first proposed in 1993. Our lab's new data support an essential role for GATA4 in parietal cells and implicate GATA4 as a crucial principal regulator of parietal cells. We are using mouse and organoid models paired with state-of-the-art techniques to comprehensively and mechanistically define GATA4's role in parietal cell fate/function.
Examining the role of GATA factors in human gastric development:
It is critical to translate what is learned about GATA function in rodent stomachs to a human system to evaluate the degree to which GATA function in gastric biology is conserved among species. Therefore, this project focuses on determining the extent to which GATA function is shared between mice and humans. Gastric organoids generated from human cells offer a model system in which GATA expression can be eliminated or amplified to examine the impact of GATA on parietal cells and overall gastric epithelial cell biology. By applying what we learn via mouse models to human biology, we expect to expand our understanding of the role of GATA factors during human parietal development and potentially in human gastric diseases.
Examining the role of GATA factors in esophageal disease:
We found that GATA4 can elicit switches in the structure of the lining of the esophagus and stomach, suggesting a role for GATA4 in metaplastic diseases. Esophageal metaplasia, known as Barrett's esophagus, occurs when columnar epithelium with gastric and intestinal identity replaces the stratified squamous esophageal epithelium. Individuals with Barrett’s esophagus have an elevated lifetime risk for esophageal adenocarcinoma, a deadly cancer with a less than 20% five-year survival rate. Esophageal cancer is currently the seventh leading cause of cancer-related deaths worldwide and is the fastest growing type of cancer in western countries. Advances toward prevention, diagnosis, and treatments have been limited because the basic mechanisms underlying the progression from normal to cancer are poorly defined. Therefore, we are examining GATA4's role in Barrett’s esophagus and cancer using unique mouse lines generated in our lab. We expect that our novel models will open a new avenue for discovery into the mechanisms of esophageal cancer and provide a model to screen novel esophageal cancer drugs.
Publications
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(Stabenau KA, Samuels TL, Lam TK, Mathison AJ, Wells C, Altman KW, Battle MA, Johnston N.) Laryngoscope. 2023 Jan;133(1):59-69 PMID: 35315085 SCOPUS ID: 2-s2.0-85126774243 03/23/2022
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(Ramadan R, Wouters VM, van Neerven SM, de Groot NE, Garcia TM, Muncan V, Franklin OD, Battle M, Carlson KS, Leach J, Sansom OJ, Boulard O, Chamaillard M, Vermeulen L, Medema JP, Huels DJ.) Biol Open. 2022 Dec 15;11(12) PMID: 36350252 PMCID: PMC9713296 SCOPUS ID: 2-s2.0-85142918558 11/10/2022
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(Franklin, OD, Battle, MA.) Cellular and Molecular Gastroenterology and Hepatology. 12/27/2022
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GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells.
(Stavniichuk R, DeLaForest A, Thompson CA, Miller J, Souza RF, Battle MA.) Sci Rep. 2021 Feb 05;11(1):3206 PMID: 33547361 PMCID: PMC7864948 SCOPUS ID: 2-s2.0-85100555273 02/07/2021
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(DeLaForest A, Kohlnhofer BM, Franklin OD, Stavniichuk R, Thompson CA, Pulakanti K, Rao S, Battle MA.) Cell Mol Gastroenterol Hepatol. 2021;12(4):1391-1413 PMID: 34111600 PMCID: PMC8479485 SCOPUS ID: 2-s2.0-85115766757 06/11/2021
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H+/K+ATPase Expression in the Larynx of Laryngopharyngeal Reflux and Laryngeal Cancer Patients.
(McCormick CA, Samuels TL, Battle MA, Frolkis T, Blumin JH, Bock JM, Wells C, Yan K, Altman KW, Johnston N.) Laryngoscope. 2021 Jan;131(1):130-135 PMID: 32250454 SCOPUS ID: 2-s2.0-85083103241 04/07/2020
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(Ann DeLaForest, Bridget M. Kohlnhofer, Olivia D. Franklin, Roman Stavniichuk, Cayla A. Thompson, Kirthi Pulakanti, Sridhar Rao, Michele A. Battle.) [preprint] BioRxiv. 08/18/2020
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(Roman Stavniichuk, Ann DeLaForest, Cayla A. Thompson, James Miller, Rhonda F. Souza, Michele A. Battle.) [preprint] BioRxiv. 06/17/2020
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(DeLaForest A, Quryshi AF, Frolkis TS, Franklin OD, Battle MA.) Front Med (Lausanne). 2020;7:44 PMID: 32140468 PMCID: PMC7042400 03/07/2020
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The Adult Murine Intestine is Dependent on Constitutive Laminin-γ1 Synthesis.
(Fields B, DeLaForest A, Zogg M, May J, Hagen C, Komnick K, Wieser J, Lundberg A, Weiler H, Battle MA, Carlson KS.) Sci Rep. 2019 Dec 17;9(1):19303 PMID: 31848396 PMCID: PMC6917708 SCOPUS ID: 2-s2.0-85076615345 12/19/2019
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Patterning the gastrointestinal epithelium to confer regional-specific functions.
(Thompson CA, DeLaForest A, Battle MA.) Dev Biol. 2018 Mar 15;435(2):97-108 PMID: 29339095 PMCID: PMC6615902 SCOPUS ID: 2-s2.0-85042765603 01/18/2018
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GATA4 Is Sufficient to Establish Jejunal Versus Ileal Identity in the Small Intestine.
(Thompson CA, Wojta K, Pulakanti K, Rao S, Dawson P, Battle MA.) Cell Mol Gastroenterol Hepatol. 2017 May;3(3):422-446 PMID: 28462382 PMCID: PMC5404030 05/04/2017
Current Members
Gabriella Metten, BS, Research Technician
Jessica Gawrys, BS, Research Technician
Lab Alumni
Ann DeLaForest, PhD, Senior Scientist, Celcuity, Minneapolis, MN
Roman Stavniichuk, PhD, Group Leader, CMIC Group, Hoffman Estates, IL
Former Graduate Students
Bridget Kohlnhofer, PhD, Senior Scientist, Aspen Neuroscience, San Diego, CA
Cayla Thompson, PhD, Senior Scientist, Fujifilm Cellular Dynamics, Madison, WI
Emily Walker, PhD, Research Investigator, University of Michigan, Ann Arbor, MI
Laboratory Staff
Charles Sauve, MD, Resident, Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, PA
Kevin Wojta, BS, Staff Research Associate II, University of California-Los Angeles, Los Angeles, CA
Ben Bondow, MD, Physician, Milwaukee, WI
Marko Ivancich, BS, Medical Student, Medical College of Wisconsin-Central Wisconsin, Wausau, WI
High School and Undergraduate Researchers
Emily Sinciscalco, BS, PhD student, Yale University, New Haven, CT
Afiya Quryshi, Student, Harvard University, Cambridge, MA