The Humans of the Wyss (HOW) series features members of the Wyss community discussing their work, the influences that shape them as professionals, and their collaborations at the Wyss Institute and beyond.
According to Jenny Tam, science helps to explain a chaotic world, and it can answer broad questions like “Where do we come from?” or specific questions like “How do brain and nervous system cells act differently in people who have bipolar disorder and people who do not?” At the Wyss, Jenny leads the CircaVent project, which aims to answer the latter while finding new treatments for the disorder. She also helps direct the Synthetic Biology platform, overseeing a variety of research activities. Learn more about Jenny and her work in this month’s Humans of the Wyss.
What project are you most involved with?
The main project I’m involved with is CircaVent. The CircaVent project aims to find new treatments for bipolar disorder. It’s a collaboration between George Church, Don Ingber, and Peng Yin’s groups. It’s a multidisciplinary, collaborative effort that truly embodies the spirit of the Wyss.
We have transcriptomics data, which shows us the presence and amount of RNA, from human brain organoids derived from bipolar and control patients. Using that data, our CogniXense algorithm predicts existing drugs for other conditions that could reverse bipolar disorder and its symptoms. We’ve created a drug screening platform where we treat organoids with our predicted drugs and compare the results to well-known treatments for bipolar disorder, like lithium.
To determine if the drugs are effective, we look at neural activity. What I mean by that is neurons will fire at a certain frequency, and there’s a difference in that rate between bipolar organoids and control organoids. We’ve seen that one of the predicted drugs shows a reversal of that neuronal firing, where the bipolar organoid treated with the drug has a firing pattern like that of a bipolar organoids treated with lithium or control organoids.
Now, with Ninning Liu, a member of Peng Yin’s group, joining the project, we can use spatial sequencing to better understand where in the brain the differences in transcriptomics data between bipolar and control patients are coming from. This helps us to understand cellular behavior.
We’ve also brought in Bogdan Budnik, who specializes in proteomics, or understanding proteins and their functions. He’s able to look at different neuronal cell types and see which proteins are affected by different drugs, which helps us understand the mechanisms by which these drugs are acting. With information from both of them, we can iterate and find more drugs that could treat bipolar disorder.
Key members of the team including Katharina Meyer, Mariana Garcia-Corral, Ayush Noori, Michelle Yue, Vivi Dang, Michael Lewandowski, and Shad Morten provide key research insights that move the project forward.
What real-world problem does this solve?
Lithium was first discovered for use for bipolar disorder probably in the mid-1960s – it was approved by the FDA in 1970. That’s over 50 years ago, so a whole generation ago. Lithium has severe side effects and about 30% of those who are taking it don’t see an improvement in their condition. The hope is that our work will uncover more effective treatments to help people who have bad side effects, don’t respond, or for whom lithium is only somewhat helpful.
What is your specific role on the team and within the Synthetic Biology platform?
So, on the CircaVent team, I’m the project lead. We’re all so thrilled to have recently received a grant from Breakthrough Discoveries for thriving with Bipolar Disorder. My job includes ideation, experimental design, determining the research direction, and serving as the overall leader.
For synthetic biology, I help manage the platform. We’re kind of like a big family, and we try not to have borders between different faculty labs and different departments. George Church has a large lab, which is divided into two areas – about half are part of the Wyss and the others sit at Harvard Medical School’s Department of Genetics. I serve as a liaison between the Wyss and Genetics. My role is to oversee and help direct projects for the folks that sit more on the Wyss side. I give advice and scientific feedback, and depending on the project I might help steer them in different directions. Pam Silver is also in the synthetic biology space, so I facilitate collaborations and try to be inclusive of her people too. The Wyss really works well in that way. The signs on our lab doors say “collaboratory,” and we really mean it. We’re trying to share knowledge, resources, and ideas.
What brought you to the Wyss?
I did my Ph.D. at Tufts University, funnily enough with David Walt, who is now a Core Faculty member here. Much of my work was in tool development and design for sequencing-based applications, mostly towards advanced microscopy-based techniques. Because a lot of this was optics-based, we had to make our own equipment, which is very much in line with the Wyss, where when things don’t exist, you make them.
I really enjoyed having ideas and seeing them come to fruition, but I wanted to understand the hypothesis-driven side as well. So, I did my postdoc at Mass General Hospital designing molecular imaging probes for diseases like cancer and Alzheimer’s, and transitioned to a faculty position there.
Then I realized I wanted to come full-circle and bring my knowledge back to academia. I have formal training in biology and immunology. That, along with my tool development experience, made me uniquely capable of meeting the needs of the clinicians and users on the engineering side. The Wyss gave me the perfect opportunity to do just that.
What value does the Advanced Technology Team bring to researchers at the Wyss?
First, the Advanced Technology Team brings their vast research experience. I’ve been around the block for a while now – I’ve seen science go from early stages to reaching consumers. When large-scale DNA sequencing was really starting to take off, I saw Illumina come out of the Walt lab. Seeing what we’d worked on in the lab go through the commercialization pipeline allowed me to understand the whole trajectory of a product. And that’s just me – all the ATTs bring experience from industry or product development to the Institute.
Advanced Technology Team members also have great networks they can share. We can help younger scientists connect with industry or academic experts or collaborators. Those of us who have been at the Wyss for a while also have an institutional memory. We know what works and what doesn’t.
How do your previous experiences inform the way you approach your work today?
I come from a very diverse lab experience, so I’ve been exposed to a lot of different people and situations. In undergrad, I got a degree in engineering where my program was only 30% women. Then, I did my postdoc in a more biological, clinical setting where there were a lot more women. On the personal side, I come from a rural background where the education is different than it is in the Boston area. Those experiences give me empathy for people and their struggles, which is important because science can be intimidating. Overall, my philosophy is to be more inclusive than exclusive, since I see that so many people have different things to offer.
I’ve also been blessed to work with very gifted scientists on incredible projects. Working with George Church is amazing and has provided scientific and creative vision. David Walt gave me a fantastic graduate experience where I first learned scientific innovation. During my undergraduate experience at Caltech, I worked in Nate Lewis’ lab on a project where we we were making electronic sensors to be used as part of an electronic nose. We were collaborating with the NASA Jet Propulsion Lab in Pasadena, CA, and some of our samples went onto the space shuttle. John Glenn worked with some of my samples! As an undergraduate, that was a life-changing and empowering experience. So, whenever I am working with students or any sort of trainee, I want them to be empowered as well. I don’t want them to feel like a rung on a ladder, but rather like an impactful part of a team.
What is your biggest piece of advice for an academic scientist looking to translate their technology?
You must have a really solid team with great chemistry and a drive to do good science together. I think that’s evident in the CircaVent project. There are many great scientific ideas out there, and our idea is great, but what makes the real difference is our team that works together well, communicates, and feels motivated to help each other. Each member is humble in their own respect.
What inspired you to get into this field?
Science helps explain things in a chaotic world. It can answer deep philosophical questions, like Where did we come from? What are the origins of life? It’s deeply meaningful to help humans understand their role in the world, and if they desire how to help shape or benefit it.
Specifically, science can also help solve a lot of the challenges facing our world, like pollution and climate change. As a human, I feel somewhat like I’ve contributed to many of these manmade problems. It’s helpful to be able to sit and focus on a question that could actually impact people or address these larger issues. I find it rewarding and satisfying.
What continues to motivate and excite you?
The scientific questions we can answer excite me, and currently I’m interested in mental health and neurodegeneration. CircaVent can help us understand what these cells are doing in a specific psychiatric disorder or state. Zooming out, it’s great to see the impact we could make by better understanding the brain and how different drugs are interacting. If we could find a potential treatment, that would be incredible. I also try to bring the enthusiasm I had interacting with patients at Mass General here.
What are some of the challenges that you face?
I just don’t think there’s enough time to do all the things I’m excited about!
What’s something unique/fun about you that someone wouldn’t know from your resume?
I used to be interested in fashion and art, so I spent a summer interning for Hillary Clinton’s dress designer. Her name is Connie Fails, and she designed the outfit and coat Hillary Clinton wore for the 1993 Presidential Inauguration. She is also from Arkansas, like me, so that’s how we got connected.
When you’re not at the Wyss, how do you like to spend your time?
I like to spend it outside and in a quiet place. My brother-in-law owns a farm, and I really love weeding and digging potatoes. Volunteering there doing farm work and gardening are both meditative for me. I’m also a mom, so I go to soccer and other activities with my kids.
I also engage in science advocacy activities. I volunteer with Science Club for Girls, where I try to show students that science is everywhere in their lives, even if they don’t realize it.
If you had to choose an entirely different career, what would it be?
I don’t know. I‘ve asked myself this before and I keep coming back to this job. I believe you must do what you love.
What does it feel like to be working on cutting-edge technologies that have the potential to make a real and significant impact on people’s lives and society?
It feels both powerful and humbling: powerful that you can have such an effect on people, but I also understand that I’m not the only person out here and we’re all working together. I couldn’t do this by myself.