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Frederic Vigneault on Developing Therapeutic Technologies to Improve the Quality of Life for Patients

The Humans of the Wyss (HOW): ATT Edition series highlights members of the Wyss Advanced Technology Team (ATTs), showcasing their role, their work, the influences that shape their approach, and their collaborations at the Wyss Institute and beyond. Reliant on strong technical expertise, diverse product development experience, and a focus on end-user needs, ATTs translate high-risk technologies into innovative solutions to advance society.

When Frederic Vigneault joined the Wyss after working in industry, he first reaction was that the Wyss was like a science playground, with its constant stream of new ideas and opportunities to explore and translate innovations. He is currently working on three therapeutic Validation Projects as a member of the Advanced Technology Team. Learn more about Frederic and his work in this Humans of the Wyss: ATT Edition.

What projects are you involved with?

Photos for CogniXense team highlight
Senior Staff Scientist and member of the Advanced Technology Team, Frederic Vigneault. Credit: Wyss Institute at Harvard University

In the past few years, I’ve been involved with a number of Validation Projects. Right now, I’m most involved with CogniXense, CircaVent, and a project on engineering bacteria to prevent dysbiosis. CogniXense is a biological modeling and drug screening platform, mostly focused on finding therapies for rare genetic diseases. CircaVent is led by Jenny Tam and uses the technology behind CogniXense as well as organoid screening to find a treatment for bipolar disorder. In both cases, I’m involved in designing the overall experiments and giving input as they are performed.

The final project is led by Andres Cubillos-Ruiz and involves engineering bacteria to prevent dysbiosis, which is a microbial imbalance. By the time I joined the project, he had done a lot of the lab work. So, instead of designing the experiments like I am doing for the other projects, I’m taking on more of an advisory role. For example, when COVID-19 slowed lab work down, I suggested Andres participate in Activate Bio, an entrepreneurship program designed to help scientists learn about commercializing their technologies. Through this, he has received more mentorship on the business development side, which is going to be invaluable as he works to translate this technology out of the lab and get it to patients. Since I have been in the field longer, I can let him know about resources like this that are available to him.

What real-world problems do these therapeutic technologies solve?

In the case of CogniXense, it’s to find drugs for specific diseases, mostly rare genetic disorders. It is very difficult for scientists to find the biological pathways related to cognition, memory, and behavior. That makes finding drugs to treat cognitive and behavioral disorders challenging. CogniXense allows us to develop treatments for these complex disorders using its drug prediction algorithm, diseases models, and screening instrument. Rett syndrome, a severe neurological disorder, is one of the first applications.

CircaVent is trying to find drugs for bipolar disorder. It is poorly understood. One thing we do know is that one of the symptoms is disordered sleep, which is something we can model using the CogniXense platform. If we can find a drug to fix the sleep disorder by example, it could help us discover other effective treatments, or at the very least it will improve the quality of patients’ daily lives. The team is also using organoid screening as another method of finding effective treatments for bipolar disorder.

The third project is trying to prevent complications related to damage to the gut microbiome resulting from antibiotics. When you get an antibiotic treatment, especially a strong one, the targeted infection is not the only bacteria affected. The good microbes are disturbed, which can lead to disease. This microbial imbalance, known as dysbiosis, makes you susceptible to other infections, like C. difficile, and if left untreated it can cause inflammatory bowel disorders and even cancer.

There aren’t many effective treatments for dysbiosis. As such we are looking to engineer an effective probiotic to prevent dysbiosis from happening.

What is the biggest difference between your work in industry and your work at the Wyss?

Wyss Institute 10th Annual Retreat at the Seaport World Trade Center in Boston, November 15, 2018
Frederic and his colleagues at the 2018 Wyss Retreat, celebrating the Wyss’ ten year anniversary. Credit: Wyss Institute at Harvard University

Before joining the Wyss, I worked at SRI International, a large non-profit research corporation and a powerhouse of innovation. They do a lot of contract research. A lot of cool stuff comes from SRI, like the technology behind Siri and the first computer mouse. When I joined the Wyss, some surface-level differences were that SRI was a lot older than the Wyss and a lot bigger – there were about 2,500 people working there, which is about five times the size of the Wyss now. Another big difference was in the rigidity. Because your time was billable, you had to keep a detailed record of your activities with corresponding codes. There was still some room to make organic connections, form new collaborations, and  pitch new projects if they fit our skillsets and had a good chance of finding external funding. The Wyss Validation Projects resemble that, but with more freedom and there is internal funding. So, the Validation Projects are more flexible and they can be riskier.

At the Wyss, it’s like being in a scientific playground. There’s an opportunity for more exploration and risk-taking than I had in industry.

Frederic Vigneault

At the Wyss, the workforce is younger, and because positions like postdocs and research assistants are easier to recruit, you’re constantly getting fresh ideas with these new people. Here, it’s like being in a scientific playground. There’s an opportunity for more exploration and risk-taking than I had in industry. It’s a hamlet of dreams. You’re free to pursue your ideas.

How does your industry experience inform the way you approach your work at the Wyss?

Early on, I think my industry experience had a greater impact. We did not have an aspect like the Validation Projects, so I focused on trying to fix projects so they could work immediately or find what would not work so we could move on quickly. Over time, my approach has changed. Working at the Wyss has taught me to spend more time surveying all of the possibilities for a project and not to fixate on having to do things the way you originally planned. The infrastructure and resources at the Wyss allow us to try things many different ways until we get the best solution. Outside of academia, you don’t always have time for this kind of exploration because there’s more pressure to reach the goal sooner. I think my time at the Wyss has actually had a positive impact on the way I approach my work. That being said, I still focus on performing the killer experiment, the one that tells you whether it’s ever going to work the way you envisioned it, or if you need to find a new way.

Looking back, what inspired you to get into this field?

I’ve always liked natural sciences, so I don’t think it was ever a question whether or not I’d be a scientist. In high school I was at least halfway decent in pretty much every class, and by picking the science and engineering track I felt like I wasn’t closing any doors. I did my undergraduate studies at a small college, mostly focused on ecology. I studied entomology, ornithology, zoology, and plant biology. There was not much human biology. Natural phenomena interested me more than human biology anyway, which is interesting considering what I do now.

The collaborative and multidisciplinary spirit at the Wyss opens up the possibility of doing completely different things.

Frederic Vigneault

Synthetic biology fits well with my interests because it allows you to program the living to do something. The way we learned about biology was often by killing the living to study it, but with synthetic biology you’re keeping it alive and making it do something that’s directly useful to humans, whether it be materials, medicine, or food. Until I got to the Wyss, I never imagined I would do anything related to diagnostics, but I ended up working on the molecular diagnostic technology that was licensed to Sherlock Biosciences. Now I work on therapeutics. The collaborative and multidisciplinary spirit at the Wyss opens up the possibility of doing completely different things.

What excites you the most about your work?

You see people working in the lab and almost every day, when you make a breakthrough, whether it be very small or large, you can tell that pretty much everybody is excited. It might be that somebody hits a snag and figures out a way around it, or they were missing something yesterday and they figured it out today. You see the smiles and it’s just very cool. I love seeing the excitements of small successes, which eventually are going to build to a big success.

I love seeing the excitements of small successes, which eventually are going to build to a big success.

Frederic Vigneault

What are some of the challenges that you face?

Frederic Vigneault on Developing Therapeutic Technologies to Improve the Quality of Life for Patients
CogniXense, one of the Validation Projects Frederic is working on, includes a drug screening instrument called a TadPool. Credit: Wyss Institute at Harvard University

My biggest challenge lies on the right side of the technology development pipeline where the technology is translated into the real world. The projects I’m working on are outside of the norm. For example, with CogniXense, we’re looking at why the pharma industry struggles to make effective treatments for rare diseases, especially those affecting the central nervous system. It’s a very tough problem, but they have a narrow, focused approach and we’re suggesting they try something different in parallel, as a complement to their current work. It doesn’t immediately jump out to them as a necessity – we need to prove it’s useful. We know it can be – we’ve seen it with our case study on Rett Syndrome, where we effectively modeled the disease, used our computational model to predict an effective treatment option, and screened it. In a pre-clinical model for Rett our compound performed better than the most advanced drug that is now in Phase 3 clinical trials for Rett syndrome.

This is also the case with the project on engineering bacteria to prevent dysbiosis. The main challenge is not the science, it’s on the business side, where we have to convince people that a proactive strategy for preventing it and the ensuing complications are a problem that needs to be solved.

We’re working to find the best way to communicate our message. As scientists, we’re not well-trained in commercialization. We’re trained to do science. In my time at SRI and at the Wyss, I’ve seen many successful spin outs. It’s never easy. The business development resources available at the Wyss are constantly improving. I hope this challenge continues to get easier as time goes on.

When you’re not at the Wyss, how do you like to spend your time?

My wife, my daughter, and I love to go hiking in state parks. We probably visited close to 50 in the past 12 years. It’s easy, they are everywhere. When we moved from Quebec to Virginia, we went to some parks that many of my colleagues and neighbors who had been living there for a while had never heard of. We were in the Shenandoah Valley, so people knew about the Skyline drive, but you could just as easily go the other way, get to West Virginia, and hike there as well. It’s the same thing around here – we’ve enjoyed exploring the nature in the area, including the beaches where you can find small critters.

What’s something unique about you that someone wouldn’t know from your resume?

Frederic Vigneault on Developing Therapeutic Technologies to Improve the Quality of Life for Patients
These are some of the chickens that Frederic has living in his backyard. Credit: Frederic Vigneault

We have 12 chickens living in our backyard. There are six different breeds, two of each. My wife grew up on a chicken farm, and one day we’d love to have a full farm, but right now we don’t have enough space. For now, we’re lucky to live in a town where we’re allowed to raise chickens. They’re all female chickens, we can’t have a rooster. They’ve actually just started laying eggs again. At the end of fall, when the days get shorter, they stop. Now we’re back to calling up our neighbors and offering them fresh eggs.

If you had to choose an entirely different career path, what would it be?

It would still involve science. If I had a lot of money, in addition to a farm, I’d like to have a coffee plantation, but I would want to understand the process of how coffee is made from start to finish. I’d like to learn how it impacts the soil, the workers, and the people drinking it. So this would still be an experiment of sorts – like a coffee institute.

What does it feel like to be working on cutting-edge technology that has the potential to have a real and significant impact on people’s lives and society?

We’re all members of a strong community doing our part to make a significant impact.

Frederic Vigneault

It feels good. I think that having an impact is what everybody wants to do, big or small. Whether people do the basic science or more translational science they cannot really predict where their efforts are going to take them. For my part, I’m hoping to help patients by bringing attention to some less recognized health problems and being part of the process to take therapeutics that could assist them to market. I think everyone at the Wyss is doing their best to make an impact. For example, even someone not directly involved in the science may help in the hiring process of a person who makes a breakthrough discovery that one day saves a patient’s life. You really never know. We’re all members of a strong community doing our part to make a significant impact.

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