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Maxime MAHE



### **Short CV:** **PhD in Neurogastroenterology at the University of Nantes, INSERM U913, France.** In 2012, I obtained a PhD from the University of Nantes, in the Neuropathies of the Enteric Nervous System and Digestive Diseases Unit, in Neurogastroenterology. Initially, my PhD research was focused on the study of enteric glial cells and their impact upon neuronal protection and intestinal barrier functions. Most of my research work was dedicated to the enteric glial cells and their role both in the control of intestinal epithelial cell growth and proliferation, and in neuroprotection. **Moving to Cincinnati Children’s Hospital.** In 2012, I joined the Division of Pediatric General and Thoracic Surgery at CCHMC, under the leadership of Michael Helmrath, MD, MS. I worked on developing new methodologies for the study of murine and human intestinal stem cells. The aim of my research was to develop and use intestinal stem cell culture techniques to study the mechanisms that result in regional specific intestinal stem cell patterning. With the goal of studying regional patterning in the small intestine, we were the first group to successfully generate 3-dimensional intestinal human PSCs and show functional maturation following engraftment into mice. Having worked extensively on the enteric nervous system during my PhD and using this recently published PSC-derived human gut, I decided to build on that model to incorporate an ENS. For this project, I have been awarded a two year pilot project from the Cincinnati Digestive Health Center, a three year research scholar award in neuroenteric disease from the American Gastroenterology Association - Athena Troxel Blackburn and a NIH K99 Career Development Award. **Joining INSERM 1235 in Nantes, France.** In 2017, I have been recruited as a junior assistant professor (Inserm CRCN) to establish a research program on the effects of the enteric nervous system on intestinal development using innovative approaches. ### **Research Goals in the Lab:** The use of human pluripotent stem cells offers great avenues to generate human tissues. The understanding of intestinal development and its translation to human pluripotent stem cells, allowed the field to move forward in understanding intestinal development and gastrointestinal diseases. Our lab has developed model systems of the human intestine with the endeavor to study gastrointestinal physiopathology. Using human pluripotent stem cells, we were able to generate a human intestine reassembling human intestinal features including and enteric nervous system (ENS). The use of iPSCs-derived organoid models represent a real opportunity to expand our knowledge into the effect of ENS on intestinal development and toward the understanding of pathophysiological processes leading to functional gastrointestinal neuropathies. In addition, our lab is also investigating forthecoming strategies that could be used to create a fully functional intestine in vitro that could be used in conjonction with microbiota and nutrients. ![Word Cloud]( #### **Main objectives of the research program :** - To characterize the role of the enteric nervous system on human intestinal development in health and diseases. - To characterize the patterning of the enteric nervous system during both neonatal and postnatal periods in health and diseases. - To develop strategies to bioengineer human gastrointestinal tissues (organoids).


Intestinal Organoids: New Tools to Comprehend the Virulence of Bacterial Foodborne Pathogens

Mayra Aguirre Garcia , Killian Hillion , Jean-Michel Cappelier , Michel Neunlist , Maxime Mahé
Foods, 2022, 11 (1), pp.108. ⟨10.3390/foods11010108⟩
Journal articles hal-03635060v1
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Intestinal Stem Cell-on-Chip to Study Human Host-Microbiota Interaction

Fatina Siwczak , Elise Loffet , Mathilda Kaminska , Hristina Koceva , Maxime Mahé
Frontiers in Immunology, 2021, 12, pp.798552. ⟨10.3389/fimmu.2021.798552⟩
Journal articles hal-03509981v1
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PGI 2 Inhibits Intestinal Epithelial Permeability and Apoptosis to Alleviate Colitis

Camille Pochard , Jacques Gonzales , Anne Bessard , Maxime Mahé , Arnaud Bourreille
Cellular and Molecular Gastroenterology and Hepatology, 2021, 12 (3), pp.1037-1060. ⟨10.1016/j.jcmgh.2021.05.001⟩
Journal articles inserm-03287962v2
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Modeling Gastrointestinal Diseases Using Organoids to Understand Healing and Regenerative Processes

Alexane Ollivier , Maxime Mahé , Géraldine Guasch
Cells, 2021, 10 (6), pp.1331. ⟨10.3390/cells10061331⟩
Journal articles hal-03324435v1
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Intestinal multicellular organoids to study colorectal cancer

Musa Idris , Maria M Alves , Robert M.W. Hofstra , Maxime Mahé , Veerle Melotte
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2021, 1876 (2), pp.188586. ⟨10.1016/j.bbcan.2021.188586⟩
Journal articles hal-03324410v1

In Vivo Human PSC-Derived Intestinal Organoids to Study Stem Cell Maintenance

Simon Vales , Holly M Poling , Nambirajan Sundaram , Michael A Helmrath , Maxime Mahé
Methods in Molecular Biology, 2020, 2171, pp.201-214. ⟨10.1007/978-1-0716-0747-3_12⟩
Journal articles hal-03619037v1
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Secretion of acid sphingomyelinase and ceramide by endothelial cells contributes to radiation induced intestinal toxicity

Daniela Leonetti , Hala Estephan , Natacha Ripoche , Nolwenn Dubois , Audrey Aguesse
Journal articles inserm-02539662v1
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Differentiation of Human Pluripotent Stem Cells into Colonic Organoids via Transient Activation of BMP Signaling

Jorge O. Múnera , Nambirajan Sundaram , Scott A. Rankin , David Hill , Carey Watson
Cell Stem Cell, 2019, 24 (5), pp.829. ⟨10.1016/j.stem.2017.05.020⟩
Journal articles hal-02533282v1

Activation of Hedgehog Signaling Promotes Development of Mouse and Human Enteric Neural Crest Cells, Based on Single-Cell Transcriptome Analyses

Sin-Ting Lau , Zhixin Li , Frank Pui-Ling Lai , Kathy Nga-Chu Lui , Peng Li
Gastroenterology, 2019, 157 (6), pp.1556-1571.e5. ⟨10.1053/j.gastro.2019.08.019⟩
Journal articles hal-02533083v1

An Organoid-Based Preclinical Model of Human Gastric Cancer

Nina Steele , Jayati Chakrabarti , Jiang Wang , Jacek Biesiada , Loryn Holokai
Cellular and Molecular Gastroenterology and Hepatology, 2019, 7 (1), pp.161-184. ⟨10.1016/j.jcmgh.2018.09.008⟩
Journal articles hal-02537887v1

IL-13–induced intestinal secretory epithelial cell antigen passages are required for IgE-mediated food-induced anaphylaxis

Taeko K. Noah , Kathryn A. Knoop , Keely G. Mcdonald , Jenny K. Gustafsson , Lisa Waggoner
Journal of Allergy and Clinical Immunology, 2019, 144 (4), pp.1058-1073.e3. ⟨10.1016/j.jaci.2019.04.030⟩
Journal articles hal-02533221v1
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Façonner l'intestin à partir des cellules souches pluripotentes humaines

Charlotte Flatres , Élise Loffet , Michel Neunlist , Maxime Mahé
Médecine/Sciences, 2019, 35 (6-7), pp.549-555. ⟨10.1051/medsci/2019096⟩
Journal articles hal-02533078v1
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Transplantation of human intestinal organoids into the mouse mesentery: A more physiologic and anatomic engraftment site

Alexander R Cortez , Holly M Poling , Nicole E Brown , Akaljot Singh , Maxime Mahé
Surgery, 2018, 164 (4), pp.643-650. ⟨10.1016/j.surg.2018.04.048⟩
Journal articles hal-02537905v1
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Engineering a second brain in a dish

Maxime Mahé
Brain Research, 2018, 1693, pp.165-168. ⟨10.1016/j.brainres.2018.04.015⟩
Journal articles hal-02537921v1
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Mechanically induced development and maturation of human intestinal organoids in vivo

Holly Poling , David Wu , Nicole Brown , Michael Baker , Taylor Hausfeld
Nature Biomedical Engineering, 2018, 2 (6), pp.429 - 442. ⟨10.1038/s41551-018-0243-9⟩
Journal articles hal-01816387v1

Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system

Michael Workman , Maxime Mahe , Stephen Trisno , Holly Poling , Carey Watson
Nature Medicine, 2017, 23 (1), pp.49-59. ⟨10.1038/nm.4233⟩
Journal articles hal-04166109v1
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Regulation of intestinal epithelial cells transcriptome by enteric glial cells: impact on intestinal epithelial barrier functions.

Laurianne van Landeghem , Maxime Mahé , Raluca Teusan , Jean Léger , Isabelle Guisle
BMC Genomics, 2009, 10 (1), pp.507. ⟨10.1186/1471-2164-10-507⟩
Journal articles inserm-00663570v1

Effets protecteurs combinés de bactéries propioniques laitières et des acides gras polyinsaturés n-6 sur la barrière épithéliale intestinale

Mantel Marine , Julie Beaudeau , Maxime Mahé , Fillipe Luiz Rosa Do Carmo , Nassima Illikoud
Réunion virtuelle "Glande mammaire lait" / Galactinnov, réseau, Galactinnov, est porté par Pierre Germon (INRA, UMR1282 Infectiologie et Santé Publique-ISP, Nouzilly)., Nov 2021, live, France
Conference papers hal-03435200v1