Meet The Researcher

I have lived in three different continents. I am originally from Italy, where I completed my education and medical training. After my neurology residency I moved to the United States supported by a fellowship funded by the National MS Society. I was supposed to stay there for just a few years, but I ended up staying for almost 15 years. In 2019 I moved with my family to Australia where I now work at the University of Sydney. I feel fortunate to have had all these opportunities to see different places because of my passion for research. I now have three different homes around the world.

I started to work on MS during my residency, just for coincidence, but then I never left this area of research. I was asked to join the group of an Italian researcher, Dr. Gabriela Constantin, at the University of Verona. She needed help because she had just returned from the US and was setting up her own laboratory. I was happy to accept and that is how I started my journey in MS research. Initially it was more basic research, but my goal has always been to translate our findings into the clinic.

I have seen the field changing dramatically in the last 10-15 years. The number of medications now available for treating MS has increased significantly and the trajectory is still on the rise. In this landscape, from my point of view, a major breakthrough has been the introduction of infusions with monoclonal antibodies (e.g. Natalizumab and Ocrelizumab) which are very effective in controlling disease activity as well as the introduction of oral treatment.

Our project will study the role of the receptor named TREM2 in remyelination. TREM2 is expressed by microglia, the cells that function as the “guardian” of the central nervous system. Microglia has a critical role in keeping everything under control and they get activated every time there is a disturbance in the tissue or damage. Their primary role is protective, but in certain circumstances their chronic activation could be detrimental and contribute to this damage. Our research has shown that TREM2 plays a key role in mediating microglia activation in response to an insult such as demyelination. Specifically, TREM2 seems to be implicated in the clearance of myelin debris, a critical step to allow remyelination. We have shown that by activating TREM2, it was possible to increase the clearance of myelin debris and enhance remyelination. The project funded by MS Australia is looking into how to better characterise the mechanism of action of TREM2 in these pathways.

Promoting remyelination is the main unmet need in MS. We hope that by activating TREM2 with specific drugs we can promote remyelination. Importantly, treatments targeting TREM 2 are already in clinical trials for people with dementia. Therefore, positive results in preclinical models could then support a faster translation into the clinic since some drugs are already available.

I feel that working in the lab could really make a difference in the life of people with MS. We have specific questions; we formulate hypotheses and then we perform experiments to test them. The whole process is very inspiring. I am a clinician by training, and I know that what we do can really help people with MS. I have seen the landscape of MS change drastically in the past few years and this is all because of research. Being a scientist is very exciting, but it can also be very challenging. On a daily basis, it can be very frustrating. The experiments we do may not give the results we expect, despite a huge investment of time and energy. As researchers, we know that this is part of the game. Progresses seem to be minimal, but when you look back you see that over time you accumulate new knowledge. Another aspect I really enjoy in the lab is the team effort. All discoveries are the result of a collaboration and contribution of many different people working together and I think this is key for successful outcomes.