Professor Ludovic Vallier

Mechanisms controlling differentiation of pluripotent stem cells into definitive endoderm

Laboratory: Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre

Departmental Affiliation: Surgery

Biography

Ludovic graduated in Molecular biology and Immunology from the University Claude Bernard Lyon I in 1997. In 2001, he earned his PhD at Ecole Normale Superieur of Lyon in the group of Jacques Samarut, under the supervision of Pierre Savatier, studying mechanisms that control the cell cycle in mouse embryonic stem (ES) cells. Following a year in the biotechnology industry, Ludovic joined Professor Pedersen's group at the University of Cambridge Department of Surgery. In 2008 he joined the newly opened Anne McLaren Laboratory for Regenerative Medicine (LRM) as a Principal Investigator and MRC non-clinical senior fellow.　

Ludovic is respectively Professor of Regenerative Medicine affiliated to the department of Surgery and director of the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre hIPSCs (human induced pluripotent stem cells) core facility. He also recently became co-deputy director of the Cambridge Stem Cell Institute and in 2020 was elected as a Fellow of the Academy of Medical Sciences. In parallel, he has been involved in the creation of several biotechnology companies including DefiniGEN and BiliTech.

Funding

European Research Council, NC3Rs, CF Trust, Open Target, Milner Institute, Rosetrees Trust.

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LV group studies the basic molecular mechanisms controlling cell fate decisions during early embryonic development and in adult organs. For that, his group utilises human pluripotent stem cells as in vitro model of development. The resulting knowledge is then exploited for generating cells from the pancreas, liver, gut and lung. The resulting cells are then used for clinical applications including disease modelling and cell based therapy. (Credit Ludovic Vallier)

Research

Understanding the mechanisms controlling early cell fate decisions in human development has major importance for regenerative medicine. Indeed, the generation of fully functional cell types from stem cells is only achievable by recapitulating a natural succession of cell fate choice. The first event of differentiation of the embryo proper occurs at the stage of gastrulation with the specification of the three primary germ layers ectoderm, mesoderm and endoderm, from which all the cells of adult tissues are derived. The main objective of our group is to define the molecular mechanisms controlling the transition between pluripotency and the endoderm lineage generating hepatic tissue. For that, we use human pluripotent stem cells (hESCs and hIPSCs) and primary organoids as in vitro model of development to study the interplays between transcriptional networks, epigenetic modifications and cell cycle which ultimately orchestrate the organogenesis of the liver. The resulting knowledge allows the development of culture systems to produce not only hepatic cells in vitro but also pancreatic, hepatic, and gut cells. These cells are then used to model diseases or for cell-based therapy applications. We have a specific focus on metabolic disorders affecting the liver including NAFLD/NASH. Thus, our overall objective is to acquire the basic knowledge necessary for generating a diversity of cell types for clinical applications.

Vallier group 2020

Group Members

Stephanie Brown, Carola Morell, Shota Nakanoh, Anna Osnato, Alexander Ross, Fotis Sampaziotis, Rute Tomaz, Brandon Wesley, Chris Gribben, Dominika Dziedzicka, Fatima Lugtu, Katerina Zacharis, Laetitia Pinte, Marion Perrin, Marta Vila-Gonzalez, Teresa Brevini, Vasileios Galanakis.

Plain English

The objective of our research group is to acquire the basic knowledge necessary to develop new therapies against metabolic diseases affecting the liver. For that, we use stem cells to model embryonic development in vitro and to produce liver cells with an interest for cell therapy of liver failure.

Key Publications

For full list see Google Scholar

Yiangou L, Grandy RA, Morell CM, Tomaz RA, Osnato A, Kadiwala J, Muraro D, Garcia-Bernardo J, Nakanoh S, Bernard WG, Ortmann D, McCarthy DJ, Simonic I, Sinha S, Vallier L (2019). Method to Synchronize Cell Cycle of Human Pluripotent Stem Cells without Affecting Their Fundamental Characteristics. Stem Cell Reports. 12(1):165-179. PMID: 30595546/PMCID: PMC6335580
Segeritz CP, Rashid ST, Cardoso de Brito M, Paola MS, Ordonez A, Morell CM, Kaserman JE, Madrigal P, Hannan N, Gatto L, Tan L, Wilson AA, Lilley K, Marciniak SJ, Gooptu B, Lomas DA*, Vallier L* (2018). hiPSC hepatocyte model demonstrates the role of unfolded protein response and inflammatory networks in α1-antitrypsin deficiency. Journal of Hepatology. 69 (4), 851-860 PMID: 29879455/PMCID: PMC6562205 *joint authorship.
Bertero A, Brown S, Madrigal P, Osnato A, Ortmann D, Yiangou L, Kadiwala J, Hubner NC, de Los Mozos IR, Sadée C, Lenaerts AS, Nakanoh S, Grandy R, Farnell E, Ule J, Stunnenberg HG, Mendjan S, Vallier L (2018). The SMAD2/3 interactome reveals that TGFβ controls m6A mRNA methylation in pluripotency. Nature. 555(7695):256-259. doi: 10.1038/nature25784. PMID: 29489750/PMCID: PMC5951268
Sampaziotis F, Justin AW, Tysoe OC,... Markaki AE, Saeb-Parsy K, Vallier L. Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nature Medicine. 2017 Aug;23(8):954-963. PMID:28671689
Bertero A, Pawlowski M, Ortmann D, Snijders K, Yiangou L, Cardoso de Brito M, Brown S, Bernard WG, Cooper JD, Giacomelli E, Gambardella L, Hannan NR, Iyer D, Sampaziotis F, Serrano F, Zonneveld MC, Sinha S, Kotter M, Vallier L. (2016) Optimized inducible shRNA and CRISPR/Cas9 platforms for in vitro studies of human development using hPSCs. Development. 2016 Dec 1;143(23):4405-4418. PMID: 27899508

Professor Ludovic Vallier