NADIS 1.0 Interview: Santina Bruzzone
Can you tell us about your scientific journey and what drew you to the biology of NAD⁺, particularly the role of the enzyme CD38?
Santina: Yes, my interest in CD38 and NAD⁺ began with my undergraduate thesis, and I’ve continued working in this field throughout my PhD and ever since.
Originally, our focus was on what we called the topological paradox — the intriguing orientation and localization of CD38, with its active site facing the extracellular space, yet playing a key role in generating second messengers that act inside the cell. So, everything started from that topological paradox.
Okay, and could you share one of the most exciting or unexpected findings from your lab?
Santina: The unexpected finding was that we found a downregulation of CD38 expression in brown adipose tissue. To the best of our knowledge, this is the only example of CD38 downregulation, because it is known that CD38 is usually upregulated in inflammatory conditions. Its downregulation was not known, so this was unexpected.
Another important line of work in our laboratory, not directly related to CD38, involves the discovery of Sirtuin 6 inhibitors. We identified these compounds through in silico screening, and step by step, we advanced to testing them in animal models of various diseases.
What do you find the most rewarding about mentoring PhD student in an international and collaborative project like NADIS?
Santina: Yes, this is absolutely rewarding from many points of view. I am really grateful to be part of this for many reasons. You asked for the most rewarding aspects, and I will list a few.
One, for sure, is the opportunity to collaborate across Europe with our research groups. This is quite exciting for us, because sometimes I feel that our level in Italy — or at least in Genova — is a little bit lower. But being exposed to a European environment where research is more advanced allows us to stay in touch with new developments, and I’m really grateful for that.
The second aspect, which I really love about my job, is the possibility to meet young people. In this consortium, we get to work with talented, motivated, and positive young researchers. I truly appreciate this great opportunity to be in contact with them.
I think these two reasons — collaboration and connection with young scientists — are what make this experience so special. Building on that, the current NADIS project has already shed new light on how NAD⁺ is consumed. Looking ahead to a potential NADIS 2.0, what do you see as the next major step in developing therapies that target energy-consuming enzymes such as CD38?
Santina: Yes, I’m not sure this specific topic will be addressed in NADIS 2.0, but personally, I find it very interesting to explore whether antibodies targeting CD38 — which are already used in the clinic for multiple myeloma — could also be applied to other diseases characterized by inflammation. Some of these antibodies also inhibit the enzymatic activity of CD38, while others do not. It would be interesting to see whether those that do inhibit the enzyme could be repurposed for additional therapeutic purposes.
The second point, where I think NADIS 2.0 will be particularly important, concerns the growing attention around NAD⁺ and NAD⁺ precursors. They are very much “in fashion” right now — I often hear people mentioning them and asking about their use. However, there are still many open questions that NADIS 2.0 might help to answer before we can truly give evidence-based advice. Personally, when people ask me, “Should I take NAD⁺ precursors?” I say, “Well, maybe, yes.”
Thank you a lot Santina.