Professor Ludovic Vallier
Mechanisms controlling differentiation of pluripotent stem cells into definitive endoderm
Laboratory for Regenerative Medicine, Cambridge Biomedical Campus.
Departmental Affiliation: Surgery
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.
Ludovic holds a joint appointment between the University of Cambridge and the Wellcome Trust Sanger Institute where he is respectively Professor of Regenerative Medicine and Senior Faculty. He is also the director of the Cambridge National Institute for Health Research (NIHR)/Biomedical Research Centre HiPSC (human induced pluripotent stem cell) core facility.
EU-Fp7, NC3Rs, ERC, MRC, EU/IMI
LV group studies the basic molecular mechanisms controlling cell fate decisions during ealry embryonic development and in adult organs. For that, we use human pluripotent stem cells as in vitro model of development for the pancreas, liver, gut and lung. The resulting cells are also used to generate cell types relevant clinical application including basic studies of diseases and cell based therapy. (Credit Ludovic Vallier)
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 normal 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. For that, we use human pluripotent stem cells (hESCs and hIPSCs) as in vitro model of development to study the interplays between transcriptional networks, epigenetic modifications and cell cycle which ultimately orchestrate the earliest step of differentiation. The resulting knowledge allows the development of new culture system to drive differentiation of pluripotent stem cells into pancreatic, hepatic, lung and gut cells. These cells are then used to model disease in vitro and we have a specific focus on metabolic disorders affecting the liver and the pancreas. Furthermore, we are currently investigating how similar mechanisms could regulate adult stem cells self-renewal /differentiation during organ regeneration. Overall, our objective is to uncover the common mechanisms controlling selfrenewal and differentiation in both pluripotent and somatic stem cells.
Stephanie Brown, Giovanni Canu, Imbisaat Geti, Kim Jee Goh, Rodrigo Grandy, Ranna El Khairi, Pedro Madrigal, Carola Morell, Shota Nakanoh, Daniel Ortmann, Ana Osnato, Casey Rimland, Alexander Ross, Fotis Sampaziotis, Samantha Tilson, Rute Tomaz, Brandon Wesley, Loukia Yiangou.
The objective of our research group is to acquire the basic knowledge and the clinical tools necessary to develop new therapies against metabolic diseases. For that, we use pluripotent stem cells to model embryonic development in vitro and to produce liver and pancreatic cells with an interest for cell therapy of liver failure and diabetes.
- 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
- Sampaziotis F, Cardoso de Brito M, Madrigal P, Bertero A, Saeb-Parsy K, Soares FAC, Schrumpf E, Melum E, Karlsen TH, Bradley JA, Gelson WTH, Davies S, Baker A, Kaser A, Alexander GJ, Hannan NRF* and Vallier L* (2015). Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nature Biotechnology. Aug;33(8):845-52 *joint authorship. PMID: 26167629 PMCID:PMC4768345
- Pauklin S and Vallier L. (2013) The cell-cycle state of stem cells determines cell fate propensity. Cell 155(1):135-147 PMID: 24074866 PMCID:PMC3898746
- Yusa K*, Rashid ST*, Strick-Marchand H, Varela I, Liu PQ, Paschon DE, Miranda E, Ordóñez A, Hannan N, Rouhani FJ, Darche S, Alexander G, Marciniak SJ, Fusaki N, Hasegawa M, Holmes MC, Di Santo JP, Lomas DA*, Bradley A* and Vallier L* (2011). Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature. Oct 12;478(7369):391-4. *joint authorship. PMID: 21993621 PMCID:PMC3198846
- Brons IGM, Smithers LE, Trotter M, Rugg-Gunn P, Chuva de Sousa Lopes SM, Howlett SK, Clarkson A, Ahrlund-Richter L, Pedersen RA, Vallier L (2007) Derivation of pluripotent Epiblast Stem Cells from pluripotent embryos. Nature. 12;448(7150):191-5. PMID: 17597762