Innovator Profile: Randolph Ashton and Gavin Knight

Randolph Ashton and Gavin Knight, researchers in Biomedical Engineering and the Wisconsin Institute for Discovery at the University of Wisconsin Madison, have developed a novel, scalable approach to bioengineer reproducible cell culture models of brain and spinal cord development. This technological advance has profound implications for identifying neurodevelopmental toxins and developing precision medicine approaches to prevent or mitigate the severity of neurodevelopmental disorders. In their research lab, the pair focused on engineering tissues derived from human stem cells to model human brain and spinal cord development. With an idea born from this research, Ashton and Knight co-founded Neurosetta. Neurosetta utilizes human stem cell technology and principles of neurodevelopmental biology to create quick, consistent, and precise screening platforms. These platforms evaluate the effects of chemicals, drugs, and genetic factors on human neurodevelopment.

Ashton and Knight founded Neurosetta to commercialize RosetteArray™ technology, a scalable screening platform that models human brain and spinal cord development, specializing in neurodevelopmental disorders such as Spina Bifida and Autism Spectrum Disorder. This platform can be used by chemical and drug development companies to screen for the developmental neurotoxicity associated with potential compounds in their product pipelines. Currently, patients with complex neurodevelopmental disorders have little to no therapeutics to lessen the severity of their disorders. Similarly, parents with family histories of neurodevelopmental disorders have no way to prevent transmission in future pregnancies. RosetteArray™ technology efficiently detects a compound’s human developmental neurotoxicity and can be used to screen patient-specific models of neurodevelopmental disorders, offering patients risk assessments and putative, personalized therapeutic options.

We asked Ashton and Knight to discuss the impact of their technology and experience as innovators in the field of biomedical engineering:

Where did the idea for your company come from initially?

Gavin: The basis of our technology sprung from our work during my graduate studies. We were very interested in controlling the self-organizing phenomenon that we observed in cultures of differentiating human pluripotent stem cells. From this, we engineered custom cell culture plates that could harness the ability of these cells to form embryonic brain and spinal cord-like tissues in a dish. Because this process closely resembles the early stages of human neural development, we were curious if these tissues were sensitive to the same environmental and genetic factors that can cause neurodevelopmental problems. When we began investigating this, it became obvious that despite the simplicity of the tissues we were generating, the assay built around them was quite sensitive to chemicals and genetic factors that can cause developmental neurotoxicity, neural tube defects like Spina Bifida, and even Autism Spectrum Disorder pathologies during embryonic development.

How has D2P helped you, and what have you learned?

Gavin: We took part in D2P’s Innovation to Market course in the summer of 2019. D2P mentors Abram Becker and Kieran Furlong helped us narrow our target markets and pushed us to find our technology’s key value propositions.

Randolph: D2P helped fund initial proof-of-concept experiments and have been instrumental in connecting Neurosetta with interested companies and venture investor.

What other entrepreneurial resources/programs have guided you?

Gavin: We have participated in the WARF Accelerator and the SBIR Advance program hosted by the Center for Technology and Commercialization (CTC). I have taken part in the Morgridge Entrepreneurial Bootcamp at UW–Madison, and I spent a week last April (2023) at the Institute for Biomedical Entrepreneurship’s Entrepreneurship Program.

What’s your current focus with the company?

Gavin: Our current focus is to market our RosetteArray™ technology as widely as possible. The more accepted these “neural rosette” tissues become by the scientific community at large, the easier it will be for toxicologists and regulators to regard them as sufficiently representative of the human tissues they resemble.

Comparison of Neural Rosette Uniformity

Randolph: The company is working on building our customer base and increasingly demonstrated applications of the RosetteArray™ platform. Neurosetta is also working to start drug discovery activities for neurodevelopmental disorders

What are your hopes for the company moving forward?

Randolph: We hope that Neurosetta becomes a profitable contract research organization for developmental neurotoxicity screening services, including having the assay validated/endorsed by regulatory agencies. We also hope that Neurosetta can begin drug discovery programs for Autism Spectrum Disorder and Spina Bifida within the next 1-2 years.

 What drives you/why is this project important to you personally?

Gavin: Our technology can potentially to reduce prevalence of neurodevelopmental disorders and developmental toxicity in general, which is important for proper human development. Plus, more reliance on our screening technology would also reduce the burden on animals as models for testing. Further, the RosetteArray™ platform makes it easy for persons not experienced with stem cell or organoid culture to conduct such screening assays. Human health, ethics of animal experimentation, and accessibility of science are all strong drivers for me.

What advice would you give to other campus innovators who are just starting with exploring the potential of their ideas?

Gavin: Entrepreneurship takes a ton of time and energy. So it’s best to be critical of your ideas early (i.e., who needs it? Who buys it? What value does it provide?, and proof from real potential customers). I strongly suggest they find people who will help guide them, like D2P. There are also many (free) services at UW-Madison or in Wisconsin for budding entrepreneurs, e.g., UW-Madison Law & Entrepreneurship Clinic and the Wisconsin Center for Technology Commercialization.

Randolph: Additionally, they should plan to be the ones to commercialize the technology and be pleasantly surprised if someone else wants to do it for them.

Is there an experience during the development of your project that surprised you or had a powerful impact on your direction? What did you learn, or how did it change your thinking?

Randolph Ashton (left) and Gavin Knight (right) working in Neurosetta’s lab

Gavin: Working with Kieran Furlong at D2P during our Innovation to Market session helped us discover a whole new target market in which our technology was a better fit and more well-received. We were also put in touch with a number of people at companies in the industry who provided invaluable feedback and one incredibly impactful collaboration. That was a significant shift in our focus and likely would not have happened (at least that early) without D2P. This cemented the idea that you need to characterize your business plan early. Otherwise you could waste valuable time pursuing customers that would never use your product.

How do you balance the time you must spend on your project with other work and life responsibilities?

Randolph: Everyone will push you to build a company as fast and as big as possible. Set boundaries in managing work and life balance. If you have a good idea/technology, you won’t miss the opportunity to commercialize it. However, you can destroy your personal life by working all the time.

Campus is full of bright minds and amazing ideas, but people often do not self-identify as an entrepreneur. Do you connect with that term, and why or why not? Is there another term you’d use to describe what you’re doing with your project?

Gavin: I don’t easily connect with the term entrepreneur. I think that term can engender (perhaps uncharitably) a more opportunistic or economically-driven motivation that people may or may not associate with. While that’s certainly a consideration for me, I’m more comfortable identifying as someone motivated by translating useful and impactful science out of the lab and into industry. Often, really cool technology never makes it beyond a university lab bench, and that’s a shame.

Read more innovator profiles from D2P