About our research group/lab
Our research
Background
Congenital intestinal disorders are rare genetic conditions that disrupt gut function from birth, leading to severe digestive problems. Depending on the tissue affected, they are classified as neuropathies (defects in the enteric nervous system), myopathies (defects in smooth muscle), or mesenchymopathies (defects in interstitial cells of Cajal). Our group mainly focuses on Hirschsprung disease and the neuropathic and myopathic forms of chronic intestinal pseudo-obstruction. Because these conditions are difficult to diagnose and have limited treatment options, understanding their genetic and molecular causes is essential for improving patient care.
Molecular mechanisms of disease
Our main goal is to uncover how genetic variants disrupt intestinal development and function. To achieve this, we use a combination of in vitro and in vivo models that allow us to investigate disease mechanisms from multiple angles. Immortalized cell lines and patient-derived inducible pluripotent stem cells (iPSCs) help us assess pathogenicity of candidate genes by revealing their effects on enteric neurons, smooth muscle cells, and other key intestinal cell types. We also use zebrafish as an animal model to observe developmental and functional defects in real time. More recently, single-cell transcriptomics have been integrated to identify missing or altered cell populations and define disease-associated molecular signatures.
New treatment avenues
By combining insights from our in vitro systems, iPSC-derived models, zebrafish studies, and single-cell analyses, we aim to translate mechanistic discoveries into new therapeutic strategies. These platforms enable us to identify promising targets, test candidate compounds, and explore gene-based approaches, with the long-term goal of developing treatments that can meaningfully improve outcomes for patients with congenital intestinal disorders.
Our projects
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Schwann like enteric glia as a new therapeutic target for Hischsprung disease.
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Hirschsprung disease: more than just enteric aganglionosis.
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ENS-Epithelial interactions.
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Epigenetic modifications in congenial intestinal disorders.
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Identifying the underlying molecular mechanisms of intestinal dysmotility in neurodevelopmental disorders (in collaboration with Dr. Geeske van Woerden and Prof. Tjitske Kleefstra).
If you would like to know more about our projects, please send an email to: m.alves@erasmusmc.nl
Key Publications
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Human Enteric Glia Diversity in Health and Disease: New Avenues for the Treatment of Hirschsprung Disease. Windster JD, et al. Gastroenterology. 168(5):965-979.e12 (2025)
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Retinoic Acid Inhibition Alters Intestinal Composition in Zebrafish: A Non-genetic Model to Study Hirschsprung Disease? Kakiailatu NJM, et al. Neurogastroenterol Motil. e70155 (2025).
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Multi-ancestry genome-wide association meta-analysis identifies novel associations and informs genetic risk prediction for Hirschsprung disease. Zhong Y, et al . EBioMedicine.115:105680 (2025).
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ATP5PO levels regulate enteric nervous system development in zebrafish, linking Hirschsprung disease to Down Syndrome. Kuil LE, et al. Biochim Biophys Acta Mol Basis Dis. 1870(3):166991 (2024).
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A combinatorial panel for flow cytometry-based isolation of enteric nervous system cells from human intestine. Windster JD, et al. EMBO Rep. 24(4):e55789 (2023).
For a complete list of publications please see:
Collaborations
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Prof . René Wijnen: Department of Pediatric Surgery.
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Dr. Kaushal Parikh: Department of Gastroenterology and Hepatology.
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Dr. Andrea Sacchetti: Department of Pathology.
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Dr. Eric Bindels: Department of Hematology.
Funding & Grants
Career opportunities
Our team
Wei Zhang, Post-doctoral fellow
Faidra Karkala, PhD student
Rose Tavenier, Master student
Bouchra Bensiamar, Bacherol student
