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Meet Yale Internal Medicine: Romina Fiorotto, PhD

March 11, 2024
by Rachel Martin

As a part of our “Meet Yale Internal Medicine” series, today’s feature is on Romina Fiorotto, PhD, assistant professor (digestive diseases and pathology)

Romina Fiorotto’s passion for the liver started back in her first human physiology class at the University of Padova in her home country of Italy.

“I remember having this specific thing in my mind of studying either liver or kidney because I was very fascinated by the physiology of these two organs,” said Fiorotto, PhD, assistant professor of medicine (digestive diseases and pathology). “I came to know a person who had a liver disease, so I decided to study the liver to learn more about this organ and conduct research related to their disease.”

It was at the end of her PhD, while she was studying at the University of Parma, that her mentor, Mario Strazzabosco, MD, PhD, professor of medicine (digestive diseases), shared that he was moving to Yale. He offered her a postdoctoral position in the Section of Digestive Diseases at Yale, which she accepted.

Now, nearly two decades later, she remains confident in her decision to join Yale. “As a liver researcher, being at the Yale Liver Center offers an incredible opportunity to not only make use of our wonderful facilities but also to share information with my colleagues who are all working on similar research. It’s the perfect environment for doing this type of research.”

Today, Fiorotto’s research is focused on understanding the basic pathophysiological mechanisms of the diseases in the biliary tree. As the associate director of the Cellular and Molecular Core at the Yale Liver Center, Fiorotto uses human samples to derive in vitro systems to model these diseases and possibly develop therapies.

As part of her ongoing work on biliary diseases, Fiorotto is leading research on cystic fibrosis-related liver disease. Cystic fibrosis is a monogenic disease, meaning it is caused by a mutation in one specific gene. While there are more than 2,000 known mutations that target the same gene, only some patients with cystic fibrosis develop liver disease.

“So, it's intriguing: why is that?” Fiorotto said.

She started looking into this question when she first came to Yale as a postdoc. She began by using cell therapy to substitute the cells in the liver that have the disease, but then an observation led her in a different direction. She discovered that in cystic fibrosis-related liver disease, the cystic fibrosis transmembrane conductance regulator (CFTR) genetic defect predisposes to liver damage by altering the innate immune responses of the biliary epithelium that is more sensitive and would overact to infectious insults. This discovery represented a paradigm shift from the classic view of cystic fibrosis-related liver disease as a mere consequence of impaired bile secretion.

Fiorotto is continuing to expand on that concept and is currently exploring the role of the gut microbiota as a potential insult. “We know that the liver and the gut are functionally and anatomically connected, and we have recently learned that microbiota in the gut affects many other liver diseases. It stands to reason that gut microbiota might also play a role in the development of liver disease in cystic fibrosis.”

In the future, Fiorotto hopes to continue to advance cellular models to develop more of a personalized approach to medicine to treat, or even cure, liver diseases. “Most biliary diseases are very rare, so it is challenging to do clinical studies,” she said. Instead, she is working to make cells and organoids with specific mutations to see which treatments can correct each mutation. She hopes that these studies will help predict how each therapy would work in a specific patient, especially when a clinical trial is not feasible.

Fiorotto recently accepted a secondary promotion as an assistant professor of pathology, where she will continue to build on her groundbreaking work into the liver. “I already work closely with pathology, and my work aligns with what they do. I want to better understand the pathophysiology of the disease. In my case, it happens to be liver disease.”

Fiorotto expects the secondary promotion will help her gain more immediate exposure to seminars, emerging research, and experts in pathology to help inspire new ways of thinking about the liver.

“I tell students and postdocs in the lab to always be curious and think about the data. If an experiment does not give you the results you expect, your data are telling you something,” Fiorotto said. “Research can be frustrating, especially at the beginning, when you are not used to your data telling you something unexpected. It can be a challenge to go back, look for a different perspective, and remain optimistic, but that’s what is needed if you are going to begin to understand what science is telling you.”

Fiorotto says working with students and postdocs is one of the most fulfilling aspects of her job. “I recently had the opportunity to be part of a former student’s thesis defense committee, and it was a beautiful experience to celebrate her achievement. As a scientist and an educator, it is rewarding to know that I helped instill some curiosity and enthusiasm for science within her.”

Since forming one of the nation’s first sections of hepatology more than 75 years ago and then gastroenterology nearly 70 years ago, Yale School of Medicine’s Section of Digestive Diseases has had an enduring impact on research and clinical care in gastrointestinal and liver disorders. To learn more about their work, visit Digestive Diseases.

Submitted by Rachel Martin on March 12, 2024