Peter Zandstra enjoying the beauty of British Columbia
Few people have made bigger contributions to the Canadian regenerative medicine ecosystem than Dr. Peter Zandstra. He is co-founder of two companies advancing cutting-edge biotechnologies for therapeutic use (Notch Therapeutics and ExCellThera, both of which are developing technologies set to transform the lives of patients) and he’s the founding Director of the University of British Columbia’s School of Biomedical Engineering (SBME), a school that is building the next generation of Canadian bioengineers. He is also the co-founder and Chief Scientific Officer of CCRM.
Recently appointed to the Order of Canada, one of the country’s highest civic honours, Dr. Zandstra is well placed to provide an insider’s perspective on the scientific leaps that will propel the cell and gene therapy industry forward. In this Q&A, we discuss his career, recent research, and predictions for the future. He shares thoughts on how artificial intelligence (AI) could assist in drug discovery, advances in our ability to engineer the decisions cells make, and his fascination with the human immune system, machine learning and tennis.
Is this how you thought your career would unfold?
No, I really think every year is different from what you thought the year was going to be, which is what makes bioengineering jobs so exciting. You can’t predict how the science will evolve, how technologies will evolve, how things like pandemics or disease prevalence, or the needs in society will evolve. One of the exciting things about my job is the variety and unpredictability, which keeps it challenging and motivating.
The other observation I have is that it’s amazing what a wonderful national and international community can be created around these types of scientific positions. Engaging with colleagues from around the world is something I wouldn’t have necessarily anticipated, yet it has been such a wonderful part of my job, and it’s been a real pleasure to see the national and international stem cell and regenerative medicine community grow and evolve.
Thinking about different areas of expertise that will be key to overcoming the challenges on the road ahead, if you could wake up with any niche of expertise tomorrow, which would you choose?
I’m continuously amazed by the depth of complexity of the human immune system and I would continue to learn there. I’m excited about some of the advances taking place in computational biology and machine learning. I don’t work in the area at all but I’m also fascinated by many of the questions that are being asked in neurobiology about how the brain works and functions, especially as a higher-order collective behaviour system – if I could pick that up by going to bed and waking up the next morning, that would be a nice niche to know!
And if you could choose a skill or niche outside of science to inherit overnight?
I could always become a better tennis player. I recently had the opportunity to see close-up some of the tennis at the Indian Wells Masters; it makes one realize how skilled these players are! I think as usual when it comes to sports, we’re always finding that boundary between our skill, ability and our ambitions. That occurs in many aspects of life, doesn’t it?
In a recent interview, you mentioned that a theme connecting your lab’s work is understanding how cells make decisions. Can you tell us about a recent project that brings us closer to engineering those decisions, and what impact progress in this area is likely to have on human health in the next decade?
One example of a recent paper that I think is quite important is one by Laura Prochazka, a scientist at Notch Therapeutics. Laura used an mRNA detection circuit that used micro-RNA-based logic circuits to detect cell state and then have that cell state report a specific transcription factor. That is the beginning of how we can use cell states to drive decisions in cell fate automatically.
I think that’s exciting because it shows us that the cell state, cell actuation type event is something that we can start to build into stem cell differentiation systems and organoid systems. In the end, I think this could influence the types of living drugs we make. For example, one could envision a cell that senses a local disease signal and then responds in a specific manner to modulate disease.
Over the longer term, wouldn’t it be wonderful if these living drugs could actually evolve their response as a disease evolves? We know that disease isn’t static and many diseases evolve as they progress. The ability to have drugs that are responsive to changing conditions could be really exciting, and this paper by Laura really starts to move us in that direction and provides a nice foundation for where we’re going with those types of technologies.
It’s always good to hear about exciting things coming from the team at Notch Therapeutics. Can you tell us about the recent paper in Nature Biotechnology that came from Notch?
I think it’s a really important paper for the cell gene and gene therapy field because it starts to define what a target product profile would be for a living cellular therapy product, like a CAR T.
Led by Dan Kirouac, it looks at clinical data from currently approved CAR T therapy products and starts to identify and develop a model that simulates how CAR T interacts with the tumour microenvironment, in this case B-cell lymphomas, and then uses that model and single-cell genomic data to extract a signature or a genetic fingerprint of what the cells, which are most clinically effective within that therapeutic product, might be. That is important for the field because it gives us the design criteria that we would then use to design therapeutics with those properties. And of course, that’s a great opportunity for companies like Notch, because they have the ability to design T-cell therapeutics from stem cells. Using the type of information provided in this paper really helps guide where we’re going, leading to better and more effective products.
If you were an early career researcher or student considering your future in regenerative medicine, what questions would you be asking?
Given where I’ve seen the field go, I would ask “How can we move toward technologies that have the same or better clinical efficacy as the complex, sophisticated technologies we have, but that are more scalable and accessible?” As an industry, we’ve made amazing progress in making new therapeutics with what is increasingly really effective clinical responses, but these products are very expensive and they’re often challenging to deliver to the large numbers of people that eventually will be able to benefit from them. A challenge we have before us is to design these technologies so that they’re scalable, robust, cost-effective and easy to deliver, even in low-resource settings so that more people can benefit from them.
This underlines the importance of initiatives that support therapeutics developers along the path from lab to life. Can you tell us which commercialization projects you’re most excited about right now?
I’m really excited about one of the business units at CCRM that focuses on identifying and commercializing promising discoveries. For many years we’ve been working on figuring out how CCRM can accelerate the creation of sustainable companies that target areas of opportunity and unmet need. I think CCRM’s process for identifying these opportunities, and for supporting early-stage companies through wet lab and early proof of principle diligence, and then also participating as investors in early funding rounds, is a super exciting one. We are starting to see it come to fruition with new companies in the pipeline that will be emerging over the next few years. I expect that this impact will grow with time and substantive partnerships that will ultimately contribute to the Canadian biotech ecosystem.
Artificial intelligence is seeing many industries grapple with its potential applications. Is AI being applied to assist in cell engineering and how will the role of AI likely evolve in your field?
Perhaps we should ask ChatGTP 😊? We’re using it increasingly in the lab in a couple of different ways. One is to help us accelerate the creation of gene regulatory networks which simulate cell fate decisions and, as the data accumulate, those tools will become more and more predictive and will be able to do more experimentation on the effects of new synthetic circuits inside cells in a purely computational way, reducing the cost of increasing the efficacy of those experiments.
Where I’d like to see it go eventually is using those types of algorithms to move towards a more discovery-based paradigm, as opposed to a validation and probability paradigm. To do that, we have to combine AI with automation and robotics, and develop ways of closing the loop between creating an experimental prediction, and then testing that prediction, and finally using the outcomes from that prediction to refine the system we’re testing. The ability to iterate along that cycle should be really exciting.
What’s your motto?
Something I really try to instill in the lab is that we should be passionate about what we’re doing, and we should enjoy what we’re doing. Science and bioengineering are really hard. Doing a PhD, doing a postdoc, and the work we undertake in the lab, these are all challenging. We should be having fun and enjoying the process of learning and struggling with the science, because the results may or may not come, but the process is incredibly valuable. That passion for finding and pushing the boundaries of knowledge is where we like to be.
Are there any opportunities you’d like to put on the radar of Signals readers?
It’s a really exciting time for CCRM, cell and gene therapy, and biomanufacturing in general right now. The Canadian government has recently announced their biomanufacturing hubs across Canada, and universities are thankful for this important investment. There’s a lot of energy and activity around new projects and programs that will prepare Canada for a robust biomanufacturing economy. We need great people to participate in this endeavour, and to contribute to the next discoveries and technology development that will emerge out of this investment.
Cal Strode
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