Data availability
All data supporting the findings of this study are available within the manuscript. Respective publicly-accessible databases (such as gnomAD and ExAC) were cited within the main text. Sharing of VSIG10L raw DNA sequencing data from familial subjects will be considered following formal written request by investigators to the corresponding author. All requests pertaining to the data in the current study will be processed in 3-5 weeks from the date of request. All data access requests will undergo in-depth review by University Hospitals Cleveland Medical Center Institutional Review Board (and by a genetic counselor) to ensure that distribution complies with ethical, institutional, and material-transfer guidelines, while ensuring strict confidentiality of the fa…
Data availability
All data supporting the findings of this study are available within the manuscript. Respective publicly-accessible databases (such as gnomAD and ExAC) were cited within the main text. Sharing of VSIG10L raw DNA sequencing data from familial subjects will be considered following formal written request by investigators to the corresponding author. All requests pertaining to the data in the current study will be processed in 3-5 weeks from the date of request. All data access requests will undergo in-depth review by University Hospitals Cleveland Medical Center Institutional Review Board (and by a genetic counselor) to ensure that distribution complies with ethical, institutional, and material-transfer guidelines, while ensuring strict confidentiality of the familial relationships. Source data are provided with this paper.
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Acknowledgements
This research was supported by Public Health Service (PHS) awards: P01 CA269019 (A.C., K.S.G., S.G.G., J.E.W., and K.G.); Case GI SPORE P50 CA150964 (K.G.), P30 CA043703 (K.G.); R01 DK118022 (K.S.G.); P30 DK034987 (K.S.G.); P30 CA014236 (S.G.G.); P30 DK097948 (A.C.); U01 CA271867 (A.C. and J.E.W.); The DeGregorio Family Foundation (K.G.), Torrey Coast Foundation GEMINI Network (K.G.), and The Gastric Cancer Foundation (K.G.). This work was also supported by the Animal Resource Center, Transgenic and Targeting core, Tissue Resources Core at the Case Western Reserve University, Molecular Genomics Core at Duke University, and Duke’s BioRepository & Precision Pathology Center (BRPC). We are grateful to the patients who opt to participate in our research. We thank our co-author, late Dr. Fujioka, who passed away recently, for his expert advice and help with electron microscopy studies that served as the foundation for understanding the biology of VSIG10L. We thank late Dr. Nathan A. Berger at Case Western Reserve University, who passed away recently, for expert scientific guidance and advice during the conceptualization phase of this study. We thank late Ms. Anne Baskin at Case Western Reserve University, who also passed away recently, for her technical assistance in animal husbandry. We thank Ms. Lakshmeswari Ravi for her technical input on the experimental methodologies used in this study. We thank the clinical gastroenterology providers who collect research samples from enrolled participants under their clinical care, especially Dr. Rahul Shimpi and Dr. Michael Feiler, as well as the Gastroenterology Clinical Research Unit staff at Duke. We thank Thomas C. Becker for performing lab-based assays in the Garman Lab to support this project.
Author information
Authors and Affiliations
Division of General Medical Sciences–Oncology, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Durgadevi Ravillah, Ramachandra M. Katabathula, Bhavatharini Udhayakumar & Kishore Guda 1.
Center for Immunotherapy and Precision Immuno-Oncology (CITI), Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
Salendra Singh 1.
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Adam M. Kresak, Joseph E. Willis & Kishore Guda 1.
Digestive Health Research Institute, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Rajesh Gupta, Wendy Brock, Amitabh Chak & Kishore Guda 1.
Herbert Irving Comprehensive Cancer Center, Division of Digestive and Liver diseases, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, USA
Yosuke Mitani & Joel T. Gabre 1.
Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
Vaibhav Jain, Emily Hocke & Simon G. Gregory 1.
The Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, Durham, NC, USA
Simon G. Gregory 1.
Department of Neurosurgery, Duke University School of Medicine, Durham, NC, USA
Simon G. Gregory 1.
Division of Gastroenterology, Department of Medicine, Duke University, Durham, NC, USA
Katherine S. Garman 1.
Cryo-Electron Microscopy Core Facility, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Hisashi Fujioka 1.
Division of Gastroenterology and Hepatology, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Amitabh Chak
Authors
- Durgadevi Ravillah
- Salendra Singh
- Ramachandra M. Katabathula
- Adam M. Kresak
- Bhavatharini Udhayakumar
- Rajesh Gupta
- Wendy Brock
- Yosuke Mitani
- Vaibhav Jain
- Emily Hocke
- Simon G. Gregory
- Katherine S. Garman
- Joel T. Gabre
- Hisashi Fujioka
- Joseph E. Willis
- Amitabh Chak
- Kishore Guda
Contributions
Study concept and design (D.R., A.C., and K.G.); Acquisition of data (D.R., A.M.K., B.U., R.G., W.B., Y.M., V.J., E.H., K.S.G., S.G.G., J.T.G., H.K., A.C., and K.G.); Analysis and interpretation of data (D.R., S.S., R.M.K., V.J., S.G.G., J.T.G., H.K., J.E.W., A.C., and K.G.); Drafting of the manuscript (D.R.); Critical revision of the manuscript (A.C. and K.G.); Statistical analysis (R.M.K.); Obtained funding (A.C. and K.G.); Administrative, technical, or material support (W.B., R.G., A.C., and K.G.); Study supervision (K.G.).
Corresponding author
Correspondence to Kishore Guda.
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Ravillah, D., Singh, S., Katabathula, R.M. et al. VSIG10L is a major determinant of esophageal homeostasis and inherited predisposition to Barrett’s esophagus. Nat Commun (2026). https://doi.org/10.1038/s41467-026-68975-3
Received: 12 May 2025
Accepted: 09 January 2026
Published: 29 January 2026
DOI: https://doi.org/10.1038/s41467-026-68975-3