A Special Interview with Prof. Matias A Avila, Newly Appointed Editorial Board Member of Metabolism and Target Organ Damage

On October 24, 2024, the Metabolism and Target Organ Damage (M&TOD) Journal interviewed Prof. Matias A Avila, our new Editorial Board member. The discussion, led by Editor-in-Chief Prof. Amedeo Lonardo, centered on Prof. Matias's recent contributions to liver disease research.

He highlighted a significant study on chronic liver disease, emphasizing that the downregulation of key identity genes results in organ dysfunction. He noted that manipulating transcription factors such as HNF4α shows promise for improving liver function, with potential applications for human Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Additionally, Prof. Matias discussed the innovative use of non-mitogenic FGF19 mRNA therapy, designed to target both hepatic and systemic metabolic dysregulation. While he acknowledged the challenges in translating this therapy for human use, he remained optimistic about future developments.

In addressing primary liver cancers, he pointed to his team’s work on identifying therapeutic targets in cholangiocarcinoma and hepatocellular carcinoma, stressing the need for new treatment strategies.

Finally, Prof. Matias shared insights into the peer review process, highlighting the difficulties editors face in securing qualified reviewers.

This interview offers valuable perspectives on advancing research and therapeutic strategies in liver disease and warmly welcomes Prof. Matias to our editorial team.

Questions for the interview:

Question 1. A recent prestigious contribution from your group (Loss of liver function in chronic liver disease: An identity crisis. J Hepatol. 2023 Feb;78(2):401-414) found that persistent downregulation of key identity genes is a strong determinant of organ dysfunction in chronic liver disease. Interestingly, manipulating the expression of core transcription factors (e.g. HNF4α) can improve structural abnormalities and ameliorate liver function. Please, comment on how these innovative approaches may potentially apply to human MASLD.

Question 2. Your group has also communicated about the potential of non-mitogenic  - Fibroblast growth factor (FGF)-19 -mRNA formulated in liver-targeted lipid nanoparticles therapy for experimental MASH in mice (Non-mitogenic FGF19 mRNA-based therapy for the treatment of experimental metabolic dysfunction-associated steatotic liver disease (MASLD). Clin Sci (Lond). 2024). It is important to pinpoint that this innovative strategy addresses both hepatic and systemic metabolic dysregulation and affects bile acid metabolism.
Which obstacles do you envisage to utilizing this approach in human MASH? And how can these barriers be overcome?

Question 3. Coming to primary liver cancer, your team has published on potential therapeutic targets in cholangiocarcinoma (Identification of PRMT5 as a therapeutic target in cholangiocarcinoma. Gut. 2024 ) and your group has also written an editorial commenting on other Reserachers’ work on this (Sweet dreams could be made of this: carbohydrate-responsive element-binding protein (ChREBP) as a target for hepatocellular carcinoma therapy. Mol Oncol. 2024). How far are we from revolutionizing medical treatment of these two most common types of primary liver cancer?

Question 4. A study from Germany, recently published in our journal ( Onion-skin type of periductular sclerosis in mice with genetic deletion of biliary kindlin-2 as tight junction stabilizer: a pilot experiment indicating a primary sclerosing cholangitis (PSC) phenotype. Metab Target Organ Damage. 2024) documents the notion that lack of phosphatidylcholine causes metabolic and inflammatory response mechanisms that ultimately lead to fibrosis in a genetically engineered mouse model of primary sclerosing cholangitis. A study from Austria (Oral Supplementation of Phosphatidylcholine Attenuates the Onset of a Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Female C57BL/6J Mice. Cell Mol Gastroenterol Hepatol. 2024) suggests that intrahepatic phosphatidylcholine concentrations are diminished in early MASH in mice and that, consistently, supplementation of phosphatidylcholine can diminish the development of MASH. Do, collectively, these findings suggest that phosphatidylcholine is a universal mediator of metabolic dysfunction?

Question 5. Let us now move to a hot topic in the publishing arena. Those who handle submitted manuscripts often meet difficulties in finding any scholars who are available to serve as Reviewers for such manuscripts. Conversely, expert Scholars like you are daily overwhelmed by innumerable requests to serve as Reviewers for multiple journals.
In this context: how do you prioritize which invitations to accept and do you feel that Reviewers, rather than volunteering, should be incentivized?

Personal Introduction:

Prof. Matias A Avila is a Professor of Biochemistry and Molecular Biology at the University of Navarra and Co-Director of the Solid Tumors Program at Cima. He earned his Pharmacy degree from the Complutense University of Madrid in 1988 and completed his Doctorate in Pharmacy at the same institution in 1992. His thesis research was conducted at the Institute of Biomedical Research of the Spanish National Research Council (CSIC) in Madrid, Spain. He then completed a postdoctoral fellowship at the Lombardi Cancer Center at Georgetown University in Washington, D.C., USA.

Since 1997, Prof. Matias has been a key member of Cima, the Biomedical Research Institute of the University of Navarra, specializing in liver regeneration, fibrogenesis, and tumorigenesis. He leads the Hepatology Laboratory within the Solid Tumors Program at Cima, contributing significantly to understanding liver disease progression and developing diagnostic and therapeutic strategies for liver cancer.

Prof. Matias has been principal investigator on 10 research projects funded by the Spanish Ministry of Economy and Competitiveness, the Ministry of Health, the Government of Navarra, the Spanish Association Against Cancer, and private entities, as well as European Programs such as Transcan. He has also collaborated on projects funded by the National Institutes of Health (NIH) in the United States. His partnerships with companies such as Moderna Therapeutics, Iteos Therapeutics, and Kintsugi Therapeutics highlight his commitment to translational research.

Focusing on epigenetic mechanisms in hepatobiliary oncogenesis, Prof Matias’s research explores novel therapeutic approaches to sensitize hepatobiliary tumors to chemotherapy. Additionally, he investigates the mechanisms driving chronic liver disease, particularly in the context of fatty liver disease.

Prof. Matias has published more than 200 scientific articles, with 70 ranked in the top decile of Journal Citation Reports (JCR). His research achievements are reflected in his H-index of 63.

As an educator, Prof. Matias teaches in the Medicine and Biochemistry programs at the University of Navarra. He has supervised 19 doctoral theses, with two receiving the Extraordinary Doctorate Award of the University of Navarra and two recognized by the Royal Academy of Doctors. He also serves on the Degree Commission in Biochemistry at the Faculty of Sciences.

Prof. Matias’s work continues to make a significant impact on liver disease and cancer research, advancing both scientific understanding and clinical practice.

Editor: Tilda Li
Language Editor: Catherine Yang
Production Editor: Yan Zhang
Respectfully Submitted by the Editorial Office of Metabolism and Target Organ Damage