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Mario Strazzabosco, MD PhD, is a Head of Faculty in Gastroenterology & Hepatology, based at the Department of Internal Medicine, Yale University.

F1000: What are you working on at the moment?

I am heading an international research group based at Yale in Connecticut and at the University of Milan-Bicocca in Milan, Italy. The group is involved in several projects, spanning from signal transduction in liver epithelia, to liver cancer and transplantation. The core project, however, is to understand the mechanisms of liver repair in liver diseases, with particular focus on biliary pathophysiology. By understanding how the biliary epithelium reacts in diseased conditions, we will be able to influence the severity and progression of liver disease.

We approach this problem by studying several congenital cholangiopathies, as disease models. For example, most recently we have studied cystic fibrosis-associated cholangiopathy and discovered that CFTR, the Cl-channel mutated in CF regulates the function of certain epithelial toll-like receptor. Studying polycystic liver disease with a similar approach, we have also demonstrated a role of polycsytin-2 in the regulation of calcium and cAMP signaling and angiogenic signaling in the biliary epithelium.

F1000: How did you get interested in the pathophysiology of liver and biliary disease?

When I was a medical student, I used to spend a lot of time at the Center for the Study of the Mitochondria of the Institute of General Pathology with Professors Azzone, Arslan and Pozzan. I learned how to prepare mitochondria from liver homogenates and I was introduced into the mysteries of the regulation of their function. My clinical clerkship gave me the inspiration to become a physician. So, combining the two experiences, I became a physician-scientist, hoping to apply the cell biology and molecular biology techniques to questions relevant for patients. The liver was the perfect organ to study, given that very little was known on its pathobiology and the therapeutic armamentarium was very thin.

F1000: Who or what inspired you? Is there someone who was instrumental in the development of your career?

I was very lucky to meet a number of inspirational teachers early in my career. I have already mentioned the people who introduced me to basic science and research. In addition, Professor Okolicsanyi from the University of Padova introduced me to the science and practice of clinical hepatology, and Professor Crepaldi, my Chair of Internal Medicine taught me a lot in terms of administration, and how to motivate and care for my coworkers. Professor Crepaldi understood my desire for a research experience abroad and helped me in securing the necessary funding.

However, Professor James Boyer was the person who was most instrumental in determining my career. I joined his lab at Yale as a postdoc more than 20 years ago. With his example, Jim really showed me how to became a successful physician-scientist in the field of liver diseases. As I progressed in my career, our relationship grew. Jim is now one of my closest friends, and I was deeply honored when I was asked to join him as a Professor at Yale, some 15 years after I left his lab as a postdoctoral fellow.

F1000: What’s the best piece of advice you’ve ever received?

They were many! They all needed to be kept in mind.

• “Chance favors the prepared mind!”
• “Be focused, but remain innovative.”
• “Think out of the box, but remember that if you are not able to convince your peers, your research is not useful.”
• “Keep your options open and reevaluate your programs and your line of research at least every 5 years.”

The best advice, however, has been the example of my mentors; to see how they tacked the different problems in their research and professional life.

F1000: What are your plans and hopes for your field?

To see liver researchers harness the basic information acquired in basic biology and translate it into better treatment and management of liver patients. It will not be soon and it will happen bit by bit, but it will happen.

F1000: Of which achievement are you most proud?

To see my mentees becoming able to fly off on their own. When I do, I think I did a good job as a researcher and as a teacher.

F1000: What is the most interesting unanswered question in biology and medicine?

Too many to mention. However I would rank autoimmunity and organ regeneration among the top.

F1000: Do you have any advice for young people embarking on a research career?

Persistence, persistence, persistence, because every rejection is an opportunity. Choose carefully your topic and your mentor and your University, but be passionate about what you are doing. If you really like what you are doing, you will do great things.

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