What drew you to your research field?
I had great mentors who are experts in the research field of liver biology and liver disease. In the USA, for my PhD, I worked with Ken Setchell, a renowned specialist in bile acid research at the University of Cincinnati. The laboratory was very active, and I was fortunate enough to be given a project to study bile acid metabolism. After that I went to the University of Minnesota as a postdoc under the mentorship of Clifford Steer. Bile acids are just fascinating signalling molecules at the intersection of metabolism and disease. I then became interested in developing bile acids as neuroprotective agents inspired by neuroscientists both in the USA and Portugal. I investigated regulated cell death, cellular function and molecular therapeutic targeting, which gave a purpose to my research career. Today my research focus is on translational sciences in drug and biomarker discovery underlying knowledge and technology transfer. We have developed promising technologies protected by global patents and explored by spin-offs that have moved to clinical trials worldwide.
What do you consider the most formative phase of your research career?
This research program is largely inspired by what I learned from my mentors and their laboratories, where it was simply impossible not to be fascinated by the discovery atmosphere. They enthused me to be a team leader establishing synergistic collaborations across interdisciplinary fields, to expand my network, to value the exchange of ideas, to get advice, and to teach students what I have learned through my research activity. We now collaborate very actively with a number of academic research groups, hospitals, healthcare and biotech companies throughout the world to identify novel disease-relevant therapeutic and diagnostic opportunities.
What do you see as the most important developments in your field in the past 5 years?
Technologies are developing fast and moving to unprecedent resolution. Combining state-of-the-art technologies such as artificial intelligence, single-cell RNA sequencing, spatial multiomics and organoid systems together with basic research is truly revolutionizing the field of hepatology and moving discovery research into application, although in several instances still requiring further consolidation to make it happen. Nevertheless, two additional considerations are warranted. First, technologies are useful tools, but you still need hypothesis-driven science. Second, as technologies become so sophisticated, collaborative work is key. Science is now more than ever sharing, being part of large teams that are international and versatile in approaches.
Tell us about one of your favourite published papers from your lab
Currently, my laboratory is interested in understanding the molecular mechanisms that drive development and progression of chronic liver disease, with a particular focus on metabolic liver disease. In one of my recent published papers, we have shown that certain forms of regulated cell death correlate with non-alcoholic fatty liver disease severity in humans and mice, linking liver metabolism, damage, inflammation, fibrosis and carcinogenesis [Afonso, M.B., et al. (2021) RIPK3 acts as a lipid metabolism regulator contributing to inflammation and carcinogenesis in non-alcoholic fatty liver disease. Gut 70, 2359–2372. http://dx.doi.org/10.1136/gutjnl-2020-321767]. Targeting this intricate signalling arises as a novel promising approach to treat steatohepatitis and arrest disease progression. In collaborative efforts, we are now using artificial intelligence drug discovery to accelerate the process of finding new improved therapeutic targets and drugs. This prompts me to mention another favourite paper, one of my most cited, which identified the mechanism of action and showed efficacy of an approved drug as an antiapoptotic agent [Rodrigues, C.M.P. et al. (1998) A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation. J. Clin. Invest. 101, 2790–2799. https://doi.org/10.1172/JCI1325], opening up a new field of research in my laboratory that supports several disease biology and drug discovery projects.
How do you explain your work to a non-scientist?
We all aspire to long, happy and healthy lives. My task is to address some of today's major health issues as well as new threats, such as the growing impact of metabolic liver disease associated with diabetes and obesity. My laboratory follows a strategy of open innovation embracing research and industry collaboration towards new, more effective and safer interventions translating to humans.
Introduction to the work of Cecília Rodrigues
The Rodrigues Lab in the University of Lisbon, Portugal has been interested in investigating novel mechanism-based molecular targets to inform drug discovery and biomarker development in inflammation, degenerative and oncogenic diseases. Cecília Rodrigues and colleagues specifically address cell signalling and the crosstalk with metabolism and interorgan communication, integrating cellular and molecular technologies with multiple preclinical and patient-derived models and samples, thus bridging laboratory research and pre-clinical development to accelerate the field and facilitate the translation from bench to bedside. She collaborates very actively with a number of academic research groups, hospitals, pharmaceutical and biotech companies throughout the world. Her group’s pioneering studies in bile-acid-related research have already developed promising small-molecule modulators of cell death/survival, protected by global patents and explored by spin-offs, which are currently in clinical trials worldwide.
More information on the FEBS Sir Hans Krebs medal and plenary lecture at the IUBMB–PABMB–FEBS Congress 2022
The Sir Hans Krebs medal is awarded annually by FEBS for outstanding achievements in Biochemistry and Molecular Biology or related sciences: https://www.febs.org/our-activities/awards/medals/
Cecília Rodrigues will be presented with the medal at the IUBMB–PABMB–FEBS Congress 2022 in Lisbon, Portugal on Monday 11th July where she will deliver a lecture on ‘Metabolic liver disease: leaping forward’: https://2022congress.febs-iubmb-pabmb.org/
Top image of post: Hepatocytes loaded with fat; by Marta Afonso, edited by Carla Pereira.