A conversation with Matthew Woodworth about mental health awareness and how his work on the CircaVent project will help improve the way we understand and treat mental health issues, like bipolar disorder
By Jessica Leff
More than one in five U.S. adults experience mental illness each year, but in 2024, only 52.1% of them received treatment. One reason people are reluctant to seek help is because of the stigma surrounding mental health. Often, that stigma comes from a lack of understanding and fear.
Unfortunately, stigma doesn’t only impact those with mental illnesses, but it also affects their families, friends, and caregivers. At least 8.4 million people in the U.S. are caring for an adult with a mental or emotional health issue. This stigma can lead to less support, isolation, and a hesitance to seek care for their relatives or friends.
One way to reduce the stigma of mental illness is by learning more about mental health and openly discussing it. Wyss Institute researchers working on the CircaVent project are taking this up a notch by not only talking about mental health but also advancing scientific understanding of the causes underlying bipolar disorder to eventually identify new and better treatments.
In August of 2024, Matthew Woodworth joined the CircaVent team as a research assistant, driven by two factors: his experience growing up with a parent with a substance use disorder and a deep fascination with organoids and their potential to transform biomedical research and human health.
We sat down with Woodworth to discuss his personal and professional background, how that informs his work on the CircaVent project, and the positive impact he hopes his work can have on patients and their families.
What got you interested in science?
I’ve always enjoyed science and math. I’m good with numbers, but I also really like tangible things. In high school, I took a biotechnology course, which gave me the opportunity to explore modern biological techniques, such as cell plating and agar streaking for bacteria. It was so cool to make the bacteria glow! I realized I enjoyed microbiology and making discoveries. So, I think it was a combination of intrinsic interest in STEM and the courses and resources I was lucky to be exposed to from a young age.
What research were you involved with during college?
I majored in biotechnology at the University of New Hampshire at Manchester and completed the accelerated master’s program, so I also have a master’s degree in biotechnology. I started working in a lab focused on neurobiology, with a strong emphasis on biomaterials. That’s where I learned to use iPSCs (induced pluripotent stem cells), which are what many organoids are derived from. In simple terms, organoids are a ball of cells pretending to be something bigger, like an organ. Scientifically, organoids start off as an aggregation of progenitor cells, and depending on which external factors are present, they will differentiate and self-organize into an organ-like structure. These 3D tissue cultures mimic the structure and function of organs and are highly useful research tools.
So, were you already making organoids?
Not quite, I made aggregates. With organoids, there’s a constant reproducibility of a group of iPSCs or some sort of progenitor cells, and they are creating some sort of mimicry of the actual organ itself. For example, in the context of brain organoids, you would have cells mimicking the frontal cortex, the midbrain, and the forebrain, with distinct layering and architecture. The aggregates consisted of cells that we grew to have certain neuronal markers, but we did not determine if they had characteristics similar to the brain, such as detecting action potentials, or what neuronal type they were, for example, dopaminergic, GABAergic, etc. But I knew what organoids were because Manchester is home to companies developing organoids, and I thought they were exciting.
What makes organoids exciting?
When it comes to better recapitulating the human body, organoids beat 2D cultures. 2D cultures are superior in certain situations. Of course, there are a lot more challenges in producing organoids, but you reap a higher level of clarity of cellular biology and how things work, specifically in an in vitro setting. I think it’s the future of any biomedical research, especially as a supplement or replacement for in vivo work. They have the potential to hugely improve and scale up research and create better insights into human-related diseases.
Organoids have the potential to hugely improve and scale up research and create better insights into human-related diseases.
What made you so passionate about applying your knowledge and skills to address mental health disorders?
That’s where my personal background comes into play. Growing up, my family life was shaky. My father was an alcoholic, and that, combined with the financial crash of 2008, which happened when I was in elementary school, led to alcohol abuse on his part and instability. I was born in Virginia, and we moved to California, then to New Hampshire, then back to Virginia, then back to California, then back to New Hampshire. We moved at least once every three years on my dad’s whim. I went to three high schools in four years. All of that moving was really destabilizing, and not something a kid should have to go through.
There’s a strong genetic component to mental health, so having a parent with a chronic addiction disorder and distant relatives with bipolar disorder got me scientifically curious, especially as I started understanding neurobiology better and doing research.
Plus, I know how scary it is to come home each day and not know what to expect from your parent. You have no control, and you want to help, but you can’t. If someone has a physical ailment, you might assist them in getting up the stairs or get them a glass of water or make them soup, but when it comes to addiction and other mental health disorders, sometimes there’s nothing you can do. So, I channeled my personal background and neurobiology experience into a drive to improve treatment for mental health disorders. That is something I can do to help.
I know how scary it is to come home each day and not know what to expect from your parent. You have no control, and you want to help, but you can’t. [Doing this research] is something I can do to help.
Thank you for sharing that. So, is that why you wanted to join the CircaVent Team at the Wyss?
Yes, it was a combination of that personal experience and my desire to work on brain organoids. When I graduated with my Master’s, I was so fascinated by the whole field of organoids, and there’s so much we still don’t know about the brain. The idea of using organoids to provide better insights into brain tissue and structure, and ultimately to better understand our brains and use that knowledge to help people, was so appealing.
For those who don’t know, what is the CircaVent project?
The CircaVent team is developing and refining a high-throughput drug screen platform that combines predictive algorithms, preclinical models, and human brain organoids to identify and test drugs that could treat mental health disorders, starting with bipolar disorder. We also aim to better understand the causes underlying bipolar disorder.
We are making brain organoids with cell lines derived from patients diagnosed with bipolar disorder. There are phenotypic differences between them and organoids derived from healthy patient cell lines. We use our organoid pipeline to make initial discoveries, then use in vivo models to validate our findings
What is your role on the CircaVent Team?
To accomplish our goals, we need reliable, high-quality brain organoids. I make all of the organoids, which are used downstream for testing and analysis. It’s fun and thought-provoking but also challenging. Brain organoids require a long time and a lot of effort to grow and mature. So, when you see your organoids actually behave like a brain, you feel a sense of accomplishment, like you’ve won a game. It’s cool to know you’ve done something so complex and interesting.
Right now, it takes a lot of specialized technical skills, grit, and determination to perform the highly manual process of creating reliable brain organoids. So, I’ve been working to automate the process to reduce variability, so we can expand our work and increase its value, efficacy, and scale. To do that, we’re combining the standardization of procedures with the use of specialized equipment, some of which we have access to through the Scientific Instrumentation @ Wyss Collaboratories Program, such as Ramona’s Vireo system and the Tecan Fluent 780 liquid handling robot. We’re excited to share this once we’ve perfected the system, to make it easier for other labs to use it in their research.
What are the benefits of working on such a multidisciplinary team?
The first word that comes to mind is empathy. Collaborating with other scientists gives you insights into their processes. By understanding what they’re doing, we can tailor some of our processes to make their lives easier. Also, it gives you diverse perspectives. They have a different way of thinking, which gives them ideas that I just wouldn’t think of. Working together can make things click in a new way and improve my day-to-day.
My team is great. Everyone has their own aspirations, but we’re working together towards a common goal. They are also incredibly helpful. I wouldn’t have been able to push for automation and grow professionally without their support, especially from Senior Scientist Katharina Meyer. When we’re in the thick of the hard work, it’s so helpful to have reassurance, kindness, and camaraderie.
Why is it important to speak about mental health?
Communicating will help people to empathize and better understand what someone’s daily life is like living with a mental health disorder. Hopefully, more openness would de-stigmatize mental illness, and it would make our society better.
It would also help people who are diagnosed with these disorders. When you get to a street corner, a crosswalk helps guide you across the street safely. When a patient gets a diagnosis, if they’ve never learned about these disorders or feel ashamed to discuss them, they might feel like they’re going into the chaos of oncoming traffic. They might not be able to find the resources to help them move forward, or cross the metaphorical street, safely. More open discussions about mental health will help guide patients in the right direction so they can get treatment.
How do you hope your work can have an impact on patients with mental health disorders in the future?
It’s an uphill battle, especially when it comes to brain-related work. But, I see the work that the CircaVent team, and thus myself, is doing as chipping away at this big, unknown black box. Eventually, with a whole bunch of research groups chipping away, we will discover something. What motivates me to keep going is the idea that if no work is done, there won’t be any results, but if I can do just some work, we’ll get to a better understanding and treatment sooner than if we don’t do anything at all.
I see the work that the CircaVent team, and thus myself, is doing as chipping away at this big, unknown black box. Eventually, with a whole bunch of research groups chipping away, we will discover something.
At the same time, by doing this work to automate the procedure of making organoids, we’re trying to democratize the process so that research groups all over the world who want to do brain-related research can use it. And that’s not limited to mental health issues; it can be applicable to neurodegenerative disorders, for example. So, the scale-up we’re working on is essential because the more brilliant minds are working on research, the more we can chip away at that box and find solutions for patients with brain-related diseases.