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At first, Giulia Monti thought she’d work in another neuroscience lab as a postdoctoral researcher. She had spent the last four years earning her PhD at Aarhus University in Denmark, studying proteins called cargo receptors in Alzheimer’s disease.

But then she stumbled upon the lab of Anna Greka, a core institute member at the ӳ����ý and a nephrologist at Mass General Brigham. The Greka lab studies the mechanisms behind protein trafficking inside cells, similar to what Monti researched in graduate school, but in the context of the kidney. Greka’s team had discovered that a family of cargo receptors called TMEDs traps misfolded proteins in the kidney, leading to kidney failure. They even found that this pathway also caused disease in the eye, suggesting that therapies developed to target this “n�ǻ��” might be able to treat multiple diseases.

Monti was intrigued by the parallels with her own work on misfolded proteins in neurodegeneration. She began to think about how she might study her original questions in a fresh context, beyond her usual area of expertise.

“I thought that this was where I could learn the most,” said Monti, who is originally from Como, Italy, and completed a master’s degree in pharmacy at the University of Milan. “Being around researchers with different expertise challenged my thinking and broadened my learning in ways I had not anticipated. I love the idea of studying biology at its core, where the same basic principles can apply across different systems.”

In December 2022, Monti moved to the US and joined the Greka lab as a postdoctoral associate. Today, she uses induced pluripotent stem (iPS) cells, mouse models, biochemical assays, and high-throughput screening to study the role of TMED cargo receptors in Alzheimer’s disease. She also collaborates with the lab of Sam Peng at ӳ����ý, using single-particle tracking to visualize how proteins move inside neurons.

We spoke with Monti about how her childhood curiosity evolved into her current interests in neuroscience and Alzheimer’s disease, and what drives her to seek new environments in this #WhyIScienceQ&A.

What got you interested in research?

Since I started school, I’ve been driven by wanting to understand how and why things happen.  For me, acquiring knowledge wasn’t just about school, it was how I could explore and make sense of the world.

The brain has always fascinated me because it's been studied extensively and yet is still full of mysteries. I was deeply interested in biology and medicine, and I realized early on that my best fit was to directly work at the bench to contribute to the development of treatments for patients.  Science seemed to me the perfect outlet for my curiosity.

During my undergrad, I had the opportunity to work in a lab where I actually realized that a career in research was not only possible but also incredibly rewarding. The curiosity-driven aspect of academic research appealed to me because it allows you to explore multiple paths. Of course, you want to help patients, and you need to steer your path with that goal in mind. But the idea that one can fundamentally ask any question to understand mechanistic biology — that's what made research the right path for me.

What are you working on right now?

We want to learn about nodal biology to translate it into something meaningful for Alzheimer’s patients. And we actually have some interesting results. We think the TMED cargo receptors previously discovered by the Greka lab also play a role in Alzheimer's disease. We found that they can bind to the amyloid precursor protein that’s known to be linked to Alzheimer’s disease. It seems that these cargo receptors are important for the trafficking of these amyloid proteins in the early secretory pathway, and therefore they can actually play a role not only in the trafficking of the protein, but also in the processing of amyloid itself, which ultimately leads to prevention of amyloid plaque deposition in the brain.

This could be extremely meaningful for patients. Now that we have identified the target, we can begin to think more from a translational angle, exploring therapeutic possibilities that could alleviate the pathology also in Alzheimer’s patients.

What questions do you find most exciting in Alzheimer’s research today?

I think it's exciting to think about a major paradigm shift in Alzheimer's disease research. In the field, the vast majority of clinical trials focus on removing extracellular amyloid plaques deposited in the brain. However, this approach may target the disease at a stage that is already too advanced to observe substantial clinical benefits. Shifting the focus to alternative targets could redefine the way we think about the disease and treatment strategies. 

We should start looking more at the processes occurring inside neurons rather than just outside the cells, especially at the earliest stages of the disease. The amyloid in the extracellular space could be like the smoke and not the fire. Removing the smoke may provide temporary relief, but it won’t solve the problem in the long run if the fire continues to burn. By studying the early secretory pathways where proteins are sorted within the cell, even before reaching the late secretary stages that much of Alzheimer’s research currently targets — we would gain a lot of knowledge and possibly begin to shift the paradigm that way.

What advice would you give your younger self?

I would never have thought to be part of an institute such as the ӳ����ý. I'm proud of the courage it took to leave my family and friends in Italy for grad school, and of how much I pushed myself along the way. During my PhD, I went to the University of Washington to learn from a lab that specialized in iPS cells for a couple of months. Even though it was a short stay, it had a big impact on me . I could actually see myself pursuing research in the US. The environment was incredibly inspiring, and it was energizing to be around people who are deeply passionate about what they do.

And so I would advise: Do not fear change. Travel as much as you can for research, and try to experience as many different environments as you can. Don't be afraid of the challenge. You can gain a lot of knowledge from this experience. The reward will be so meaningful that the struggle will be less important.