Research Groups

Research Focus

Tissue maintenance and repair depend on the ability of cells to respond to internal and external cues, proliferate and differentiate into functional components. Aberrant regulation of this response results in disease; hyperproliferation and cancer or tissue degeneration and scar formation. In the Huch lab we exploit both the liver, as a model of extensive regenerative capacity and the pancreas, which exhibits very little regeneration potential, to unveil the biological processes that control adult tissue homeostasis and repair and their deregulation in disease. 

Our experimental strategy involves the combined use of: (1) animal models and (2) in vitro mouse and human organoid models that recapitulate key aspects of mouse and human liver development, proliferation and regeneration in culture, in a controlled environment. 

We take the following approaches:

  1. We study the different subpopulations of liver progenitors during early liver development
  2. We investigate the niche-progenitor relationship during regeneration and in disease
  3. We analyse the epigenetic mechanisms involved in the transition from a differentiated cell to an activated progenitor and from a progenitor to a differentiated cell
  4. We study the cellular heterogeneity and cellular interactions in human cancer 

Our long-term goal is to understand the principles that govern proliferation and differentiation of adult organs and tissues to gain the knowledge required to further develop our organoid cultures and potentially recapitulate organogenesis in vitro.

Selected Publications

* joined first author # joined corresponding author

2021

Lucía Cordero-Espinoza✳︎, Anna Dowbaj✳︎, Timo N Kohler, Bernhard Strauss, Olga Sarlidou, German Belenguer, Clare Pacini, Nuno P Martins, Ross Dobie, John R Wilson-Kanamori, Richard Butler, Nicole Prior, Palle Serup, Florian Jug, Neil C Henderson, Florian Hollfelder, Meritxell Huch
Dynamic cell contacts between periportal mesenchyme and ductal epithelium act as a rheostat for liver cell proliferation.
Cell Stem Cell, 28(11) 1907-1921 (2021)
Open Access   DOI

2020

Nikitas Georgakopoulos, Nicole Prior, Brigitte Angres, Gianmarco Mastrogiovanni, Alex Cagan, Daisy Harrison, Christopher J Hindley, Robert Arnes-Benito, Siong-Seng Liau, Abbie Curd, Natasha Ivory, Benjamin D Simons, Inigo Martincorena, Helmut Wurst, Kourosh Saeb-Parsy, Meritxell Huch
Long-term expansion, genomic stability and in vivo safety of adult human pancreas organoids.
BMC Dev Biol, 20(1) Art. No. 4 (2020)
Open Access   DOI

2019

Luigi Aloia, Mikel Alexander McKie, Grégoire Vernaz, Lucía Cordero-Espinoza, Niya Aleksieva, Jelle van den Ameele, Francesco Antonica, Berta Font-Cunill, Alexander Raven, Riccardo Aiese Cigliano, German Belenguer, Richard Lester Mort, Andrea H Brand, Magdalena Zernicka-Goetz, Stuart J Forbes, Eric A Miska, Meritxell Huch
Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.
Nat Cell Biol, 21(11) 1321-1333 (2019)
DOI
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Nicole Prior, Christopher J Hindley, Fabian Rost, Elena Meléndez, Winnie W Y Lau, Berthold Göttgens, Steffen Rulands, Benjamin D Simons, Meritxell Huch
Lgr5+ stem and progenitor cells reside at the apex of a heterogeneous embryonic hepatoblast pool.
Development, 146(12) Art. No. dev174557 (2019)
Open Access   DOI

2017

Laura Broutier, Gianmarco Mastrogiovanni, Monique Ma Verstegen, Hayley E Francies, Lena Morrill Gavarró, Charles R. Bradshaw, George E Allen, Robert Arnes-Benito, Olga Sidorova, Marcia P Gaspersz, Nikitas Georgakopoulos, Bon-Kyoung Koo, Sabine Dietmann, Susan E Davies, Raaj K Praseedom, Ruby Lieshout, Jan N M IJzermans, Stephen J Wigmore, Kourosh Saeb-Parsy, Mathew J Garnett, Luc Jw van der Laan, Meritxell Huch
Human primary liver cancer-derived organoid cultures for disease modeling and drug screening.
Nat Med, 23(12) 1424-1435 (2017)
DOI

2016

Laura Broutier, Amanda Andersson-Rolf, Christopher J Hindley, Sylvia F Boj, Hans Clevers, Bon-Kyoung Koo, Meritxell Huch
Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation.
Nat Protoc, 11(9) 1724-1743 (2016)
DOI

2015

Meritxell Huch, Helmuth Gehart, Ruben van Boxtel, Karien Hamer, Francis Blokzijl, Monique Ma Verstegen, Ewa Ellis, Martien van Wenum, Sabine A Fuchs, Joep de Ligt, Marc van de Wetering, Nobuo Sasaki, Susanne J Boers, Hans Kemperman, Jeroen de Jonge, Jan N M Ijzermans, Edward E S Nieuwenhuis, Ruurdtje Hoekstra, Stephen Strom, Robert R G Vries, Luc Jw van der Laan, Edwin Cuppen, Hans Clevers
Long-term culture of genome-stable bipotent stem cells from adult human liver.
Cell, 160(1-2) 299-312 (2015)
DOI

2013

Meritxell Huch✳︎, Paola Bonfanti✳︎, Sylvia F Boj✳︎, Toshiro Sato✳︎, Cindy J M Loomans, Marc van de Wetering, Mozhdeh Sojoodi, Vivian S W Li, Jurian Schuijers, Ana Gracanin, Femke Ringnalda, Harry Begthel, Karien Hamer, Joyce Mulder, Johan H van Es, Eelco de Koning, Robert R G Vries, Harry Heimberg✳︎#, Hans Clevers✳︎#
Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis.
EMBO J, 32(20) 2708-2721 (2013)
Open Access   DOI
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Meritxell Huch, Craig Dorrell, Sylvia F Boj, Johan H van Es, Vivian S W Li, Marc van de Wetering, Toshiro Sato, Karien Hamer, Nobuo Sasaki, Milton J Finegold, Annelise Haft, Robert R G Vries, Markus Grompe, Hans Clevers
In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration.
Nature, 494(7436) 247-250 (2013)
DOI