How Organoids are Driving Better Understanding of Liver Regeneration and Repair
Dr. Luigi Aloia discusses liver organoids, how he has used them for his studies, and how he anticipates organoids will impact hepatic research more generally.
What inspired you to pursue scientific research?
Curiosity has always been the driving force for me. Designing experiments is a very creative process and interpreting results requires being very open-minded and constantly updated. This makes scientific research challenging and stimulating.
Do you have a scientific idol that influenced the scientific path you’ve chosen?
The work of the 2012 Nobel Prize winners, Shinya Yamanaka and John Gurdon, has had a great influence on my scientific research. I am very lucky to work in the same institute with John Gurdon, who is a very inspiring scientist.
How has working in the same institute as Dr. Gurdon affected your work or yourself as a scientist?
Under the supervision of John Gurdon, I am organising the prestigious Developmental Biology Seminar Series, which was started in 1989 by Dr. Gurdon himself. This has given me the opportunity to have scientific discussions with him and learn from his vast scientific knowledge. Particularly, I realised how important it is to study different organisms and how having very clear approaches and staying open-minded is the key to successfully addressing biological questions of interest.
What led you to studies in your current field?
Embryonic development and tissue regeneration have always fascinated me. Understanding the molecular mechanisms driving cellular plasticity in the embryo and the adult has always been my main scientific interest.
What hobbies do you have outside of the lab?
I like photography and visual arts in general. I am also a great fan of indie rock and folk music.
Describe the focus of your current research.
My current research is focused on liver regeneration and more specifically on the epigenetic mechanisms driving cellular plasticity in the adult liver upon tissue injury.
What strategy are you using to evaluate the epigenetic status of hepatic cells? What technical barriers have you faced over the course of your research?
We are pursuing several experimental approaches including ChIP- and ATAC-sequencing. The main technical barrier is the low number of cells available.
What are the primary research techniques you use in your research?
I use a variety of molecular approaches including RT-qPCR, chromatin immunoprecipitation, immunostaining and, of course, organoid culture.
What do you consider to be the most important advance(s) in liver research in the last five years?
Organoid cultures represent a great advance in the field as they provide models for liver disease and for elucidating cellular plasticity in response to damage.
What experiments are specifically easier or possible using organoid culture systems that were not possible using other methods?
Organoid cultures allow long-term expansion of liver cells while retaining their physiological features. They represent a great advance in the field by providing models for liver disease and regeneration. Establishing cellular polarity and remodelling the extra-cellular matrix are essential processes during regeneration. Thus, organoid cultures represent a unique model in order to study regeneration and elucidate molecular mechanisms of cellular plasticity in response to damage.
Do you see any downstream advances in health care related to this greater mechanistic understanding of liver regeneration?
Novel therapeutic approaches in disease will be possible once the molecular mechanisms of liver regeneration are better elucidated. In particular, epigenetic regulators are druggable and can represent important targets for treatment of liver disease.
What impact do you see organoids having on your field? What technical hurdles remain before this can be realised?
I am sure that organoid cultures will have a great impact on the field. Designing chemically defined matrices is essential for more physiological studies. Also, co-culturing different cell types to model complex liver architecture in a dish will help in studying liver physiology and disease.
What breakthroughs would you anticipate in the next five years?
I think that there will be a huge effort to elucidate basic mechanisms driving liver regeneration. Understanding the cell-of-origin for different subtypes of liver cancer and the mechanisms of carcinogens will be among the main goals in the field.
- Aloia L., McKie M., and Huch M. (2016). Cellular plasticity in the adult liver and stomach. The Journal of Physiology. 594(17):4815-25.
- Aloia L., Gutierrez A., Caballero JM., and Di Croce L. (2015). Direct interaction between Id1 and Zrf1 controls neural differentiation of embryonic stem cells. Embo Reports. 16(1):63-70.
- Aloia L., Di Stefano B., Sessa A., Morey L., Santanach A., Gutierrez A., Cozzuto L., Benitah S.A., Graf T., Broccoli V., and Di Croce L. (2014). Zrf1 is required to establish and maintain neural progenitor identity. Genes & Development. 28(2):182-97.
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Luigi Aloia, PhD