A Conversation With Peter Zandstra,A PhD, FRSC(E)

Peter Zandstra is a Professor of Biomedical Engineering, the Chief Technology Officer of ExCellThera, and the Chief Scientific Officer of the Center for Commercialization of Regenerative Medicine (CCRM). He is a renowned stem cell scientist and has recently joined the University of British Columbia to lead the School of Biomedical Engineering and as the Director of the Michael Smith Laboratories. BCREGMEDa s Trainee Steering Committee sat down with Dr. Zandstra to discuss his scientific career, his vision for the new school of biomedical engineering and the future of regenerative medicine in BC. What follows is a paraphrased transcript of their conversation.

You are involved in a variety of activities: from basic researchA to education, to entrepreneurship. What aspect of your daily work schedule do you most enjoy?

It isna t so much what aspect of the work it is. For me, ita s about working with the students, faculty, scientists, and other professionals who are passionate about making an impact. Especially working with young people, thata s what I really enjoy. Digging into data, thinking about how to approach a problem, thinking about what a curriculum would look like, in many ways they are the same thing: you are working with someone who is interested in solving an important problem.

Can you speak about your general vision for the new school of biomedical engineering?

The world is moving to a state where cellular and molecular biology can be an engineering- and design-based science. In other words, we can start to think about how to design biological systems to either (1) test fundamental hypotheses or (2) solve clinical problems.

We now know many of the bits of the cell, we know a lot about the genome, we know much about proteins and their structure, and we have a comprehensive understanding of the cell surface. Using the cell as a basic system, we can overlay design and mathematics to create new things. Much like asking the question how do you design an airplane?A We can now start asking how do you design a cell?a or a system of cells that interact to achieve a specific purpose? How do you take systems apart? That is essentially the philosophy that Ia m trying to build as part of this new school. And, of course, part of that is designing better devices that interface with human biology. These could be retinal chips that interface with neural circuitry or many other kinds of devices. Therefore, how we define BME is basically a ?anything that talks and listens to biologya .

How has the field of bioengineering evolved since you started your career?

When I started, many bioengineers came from a process engineering background, and they would be involved in manufacturinga first proteins, and then cellsa and that still remains a very important part of whata s going on today. But bioengineering has evolved more towards driving fundamental discoveries in biology. Tools like CRISPR/Cas9 and optogenetics are great examples of technologies which were influenced by bioengineering-like initiatives and are helping reveal a lot of about how cells fundamentally work. I think this concept, that tools are enabling our understanding of biology and helping us implement that understanding to achieve transformative solutions, is running much more as a standard way of thinking these days. What we can do is dependent on the tools that we have, and biomedical engineers are experts in developing and implementing these tools.

So how do you see the field of bioengineering and regenerative medicine growing in BC?

Ia m still getting to know the ecosystem. But so far, it’s apparent that we have a number of key strengths. We are strong in the T-cell therapeutics area and certainly in hematopoiesis, and these are things that we can build on. Where we can go even further, I think, is with designing cells that are useful for therapeutic purposes that are derived from stem cells. From another perspective, we have great strengths in the fields of imaging, computational biology, and biomedical devices. These are either physical devices or computer systems that are designed to work in a clinical environment. I think there is an opportunity to bring these devices closer and closer to interacting with human biology so you really start to achieve technologies that respond to biological a ?feedback loopsa . One vision for these systems would be new so-called a ?bionic systemsa ? where you have multi-directional interactions between machines and human physiology. There areA lots of opportunities to catalyze in BC, and I am hopeful our new School of BME will play a lead role in advancing these to the next level.

In terms of regenerative medicine, with the Canadian Stem Cell Network, Medicine by Design and many growing provincial initiatives including the BC Reg Med Network, an important goal would be for these provincial regenerative medicine institutes to communicate with each other under one umbrella, and, as a country, ita s worth our while to be coordinated and strategic about how we approach regenerative medicine. Reg Med is a science that Canada has fundamental strengths in and one we should lead the world in for the benefit of Canadians.

You have co-founded multiple biotech companies, including CCRM and ExCellThera. How did you first get involved in biotech entrepreneurship?

One of the things that is ingrained into engineers during their training is the perspective of applications for their work. When I finished my PhD and moved to Boston, I started to work with a few biotech companies there, and from those experiences, I realized that in order for regenerative medicine to really have an impact on patients, you need to think about cost-effective ways of developing and implementing new products.

I was involved in an early company where they needed someone to think about manufacturing issues. I then co-founded CCRM largely to try to accelerate this process. In my lab, we typically not only think about how our fundamental discoveries can contribute to science but also about how we can take them one step further and implement them to solve biomedical problems. All of the projects in my lab are focused on solving fundamental problems, but we recognize that there are opportunities that emerge from doing that. This relates somewhat to an important idea: that Canada should capture the great science it does; that we want to create jobs for students that are in our labs and that we want to keep talented people in Canada.

In fact, we have great institutions and resources in Canada today that can enable scientists and engineers to build their careers here. One aspect of what I am trying to do is to build a Canadian ecosystem of bioengineering expertise. How can we help our students stay in Canada to build their careers and have their families here? How do we capture the great science coming out of our Country? These are questions I am constantly thinking about.

What are some important lessons you learned from your experiences in entrepreneurship?

I think going through that process really sharpens the kinds of questions that you ask. In science, we derive value from the things we learn. When you take this extra stepa to commercialize a producta you have to overlay onto that a number of additional questions which very quickly determine if you are competitive, or novel, or whether people really can use what you are creating to make a difference. Is there a market? Is it really better than what we do now? Will it solve a need? Those questions hone your focus very quickly.

The other thing thata s exciting is that these entrepreneurial experiences brought me into contact with really smart people. People who not only think deeply about science but also think about how science can be used to solve significant health problems. And that has been really fulfilling.

To finish off, what is one thing (concept, publication, or idea) emerging in the field of bioengineering that you are most excited about lately?

I am really excited about this emerging sub-field that wea re working on called a ?Engineering Developmenta . It centers on trying to understand how multicellular structures from single (stem) cells in a coordinated manner.

It is known that you can control the genetic programs that occur early in development to generate cellular structures that are reminiscent of adult tissues. But the word a ?reminiscenta is key here: while many of the cells that are found in normal tissues also appear in organoid systems, these cells, and the structures they produce, lack the architectural complexity and compartmentalization that we normally see in adult tissues (i.e., cell junctions, epithelial borders, and other formations that contribute to the normal physiological function of a tissue). So, what the heck is going on here?A Why are these two programsa expression and compartmentalizationa so independently coordinated? My sense is that is where the emergent function of the appropriately organized cell or tissue liesa beyond just the proteins and the genetic code which leads to the cell type of interest.


Peter Zandstra will be participating in a Fireside Chat alongside Dr. Fabio Rossi at the Pre-Symposium Trainee Workshop on May 8th. If you are a graduate or postdoc trainee and would like to hear more from Dr. Zandstra, click here to register for the workshop!

By Ido Refaeli (PhD Candidate, McNagny Lab)A & Elizabeth Bulaeva (PhD Candidate, Eaves Lab)

April 10th 2018