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9

Biosketch


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.

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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).


Journal articles9 documents

  • Daniela Leonetti, Hala Estephan, Natacha Ripoche, Nolwenn Dubois, Audrey Aguesse, et al.. Secretion of acid sphingomyelinase and ceramide by endothelial cells contributes to radiation induced intestinal toxicity. Cancer Research, American Association for Cancer Research, 2020. ⟨inserm-02539662⟩
  • Sin-Ting Lau, Zhixin Li, Frank Pui-Ling Lai, Kathy Nga-Chu Lui, Peng Li, et al.. Activation of Hedgehog Signaling Promotes Development of Mouse and Human Enteric Neural Crest Cells, Based on Single-Cell Transcriptome Analyses. Gastroenterology, WB Saunders, 2019, 157 (6), pp.1556-1571.e5. ⟨10.1053/j.gastro.2019.08.019⟩. ⟨hal-02533083⟩
  • Nina Steele, Jayati Chakrabarti, Jiang Wang, Jacek Biesiada, Loryn Holokai, et al.. An Organoid-Based Preclinical Model of Human Gastric Cancer. Cellular and Molecular Gastroenterology and Hepatology, Philadelphia, PA : American Gastroenterological Association, [2015]-, 2019, 7 (1), pp.161-184. ⟨10.1016/j.jcmgh.2018.09.008⟩. ⟨hal-02537887⟩
  • Charlotte Flatres, Élise Loffet, Michel Neunlist, Maxime Mahé. Façonner l'intestin à partir des cellules souches pluripotentes humaines. médecine/sciences, EDP Sciences, 2019, 35 (6-7), pp.549-555. ⟨10.1051/medsci/2019096⟩. ⟨hal-02533078⟩
  • Taeko Noah, Kathryn Knoop, Keely Mcdonald, Jenny Gustafsson, Lisa Waggoner, et al.. IL-13–induced intestinal secretory epithelial cell antigen passages are required for IgE-mediated food-induced anaphylaxis. Journal of Allergy and Clinical Immunology, Elsevier, 2019, 144 (4), pp.1058-1073.e3. ⟨10.1016/j.jaci.2019.04.030⟩. ⟨hal-02533221⟩
  • Maxime Mahé. Engineering a second brain in a dish. Brain Research, Elsevier, 2018, 1693, pp.165-168. ⟨10.1016/j.brainres.2018.04.015⟩. ⟨hal-02537921⟩
  • Alexander Cortez, Holly Poling, Nicole Brown, Akaljot Singh, Maxime Mahé, et al.. Transplantation of human intestinal organoids into the mouse mesentery: A more physiologic and anatomic engraftment site. Surgery, Elsevier, 2018, 164 (4), pp.643-650. ⟨10.1016/j.surg.2018.04.048⟩. ⟨hal-02537905⟩
  • Holly Poling, David Wu, Nicole Brown, Michael Baker, Taylor Hausfeld, et al.. Mechanically induced development and maturation of human intestinal organoids in vivo. Nature Biomedical Engineering, Nature Publishing Group, 2018, 2 (6), pp.429 - 442. ⟨10.1038/s41551-018-0243-9⟩. ⟨hal-01816387⟩
  • Laurianne van Landeghem, Maxime Mahé, Raluca Teusan, Jean Léger, Isabelle Guisle, et al.. Regulation of intestinal epithelial cells transcriptome by enteric glial cells: impact on intestinal epithelial barrier functions.. BMC Genomics, BioMed Central, 2009, 10 (1), pp.507. ⟨10.1186/1471-2164-10-507⟩. ⟨inserm-00663570⟩