A Drive to Understand Underlying Biologic Principles Made Her an Expert on Hepatic and Pancreatic Organoids
Dr. Huch obtained her PhD at the Center for Genomic Regulation in Barcelona, Spain. She subsequently studied under Dr. Hans Clevers at the Hubrecht Institute for Developmental Biology and Stem Cell Research in Utrecht, the Netherlands. She is currently a Junior Group Leader at the Gurdon Institute in Cambridge, UK. Her work focuses on tissue regeneration and developing tissue-specific disease models for the liver and pancreas.
What inspired you to pursue scientific research?
After finishing college I decided I wanted to enter science because I wanted to understand how aspirin works. It was fascinating to me that you can take a pill and it could locate your pain and relieve it. For this reason I decided to study Pharmacology. After finishing my undergraduate I felt that there was still so much to learn, I feel it was a natural decision to move on to PhD studies. I simply wanted to know more, understand more. The same happened when I decided to become a postdoctoral fellow, and is still happening now every time I look through the microscope or perform an experiment. I continuously feel as if there is more that I cannot get to; this pushes me to keep studying.
Do you have a scientific idol that influenced the scientific path you’ve chosen?
I greatly admire my former mentor Hans Clevers, who is a pioneer in stem cell biology, having contributed a number of fundamental discoveries in the field. However, the most influential scientist in my life is a scientist I have never met, Marie Curie. Her discoveries changed the way we do research, and more important, the way that many pathologies are being diagnosed. Apart from her contributions to science, I also admire her courage. Being a female scientist during a time when a woman’s role was to be at home and man dominated the scientific world was probably very difficult. Yet, her appetite for knowledge and her exceptional talent allowed her to shine, and be admired by her male peers. That is really remarkable.
What led you to studies in your current field?
The realization that I needed to understand the basic principles. We can only treat a disease if we first understand how it works.
What hobbies do you have outside of the lab?
When there is any time left I spend it with my family. Not that my family is a hobby, but it is my passion. When there is more time, I like playing the piano and cross-country skiing with my husband. We both enjoy nature very much, and hope to be able to share it with our son as he grows older.
Please describe the focus of your current research
The current research focus at my lab is understanding tissue regeneration and developing disease models for the organs we are interested in; at present, the liver and pancreas. Chronic liver disease and pancreatic cancer are strongly associated with inflammation and tissue damage, which activate stem cells and progenitor cells to repair lost tissue. Our goal is to understand the activation mechanism in order to harness it for therapeutic strategies.
What do you consider to be the most important advance(s) in liver/pancreatic research in the last five years?
The discovery of gene mutations in liver cancer, as well as the association between the different mutational pathways and the aetiology of the disease (whether mutations associated with alcohol syndrome are different in patients with viral hepatitis, for example) has been quite revealing in my opinion. Also, our ability to grow liver and pancreatic tissues ex vivo, either from pluripotent stem cells or directly from adult tissue, has been a great breakthrough in the field, opening up many possibilities for research and therapy.
What breakthroughs would you anticipate in the next five years?
I believe being able to study cell-to-cell interactions, model diseases that are human-specific and being able to obtain endocrine cells ex-vivo, despite all of these being very challenging prospects, are potential breakthroughs.
What has the adoption of organoid cultures added to your research? What types of biological questions has this technique enabled you to probe?
It has allowed us to model diseases, from both hepatocytes and the duct compartment. More recently, organoid culture has allowed us (in collaboration with the Cuppen lab and Ruben van Boxtel and the Clevers lab at the Hubrecht Institute) to prove that proliferating stem cells have their own particular way to deal with the accumulation of base substitutions in coding genes.
What impact do you see organoids having on the liver and pancreatic research fields? What technical hurdles remain before this can be realised?
I think both systems will be very important new tools to model human diseases of the liver and pancreas. However, we are still unable to model the pathogenesis of these diseases in full. At present we can only model the epithelial counterpart, and we still need the mouse model to help us mimic the fibrosis or inflammation occurring in these diseases.
- Broutier L et al. (2016) Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nat Protoc 11(9): 1724–43.
- Hindley CJ et al. (2016) Organoids from adult liver and pancreas: Stem cell biology and biomedical utility. Dev Biol 420(2): 251–61.
- Huch M & Koo B-K. (2015) Modeling mouse and human development using organoid cultures. Development 142(18): 3113–25.
- Huch M et al. (2015) Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver. Cell 160(1–2): 299–312.
- Huch M et al. (2013) Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J 32(20): 2708–21.
- Huch M et al. (2013) In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 494(7436): 247–50.
- Barker N et al. (2010) Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6(1): 25–36.
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Meritxell Huch, PhD