Past, present and future: Academic life from the lens of Dr. James Piret

Writing by Santanu Sasidharan from the Tokuriki lab, Michael Smith Laboratories

This is the fourth and final article in our Past, Present and Future series, where explore the journeys of inspiring faculty whose work is shaping the future of research. In this instalment, we feature Dr. James Piret. Dr. Piret is a professor at the Michael Smith Laboratories and the Department of Chemical & Biological Engineering at the University of British Columbia. Dr. Piret’s research focuses on mammalian cell biomanufacturing, developing innovative methods, devices, and data analytic technologies to improve access to therapies for diseases such as cancer and diabetes. Advancing these types of applied science goals, close to real world applications, is best achieved by multidisciplinary teams. Dr. Piret has led many teams, collaborating with stem cell and immune cell biologists, as well as chemists, engineers, and often industry partners.

1. How has your research evolved and impacted your field?

Inspired by an older sister, I developed a fascination for biology at a young age. With an aptitude for math, I started my academic journey with a bachelor’s degree in applied mathematics to biochemistry. This led me to explore the intersection of engineering and the life sciences, and ultimately into the field then known as biochemical engineering.

After initially doing research on biofuels, at that time hopelessly more costly than petroleum, I transitioned into mammalian cell bioprocessing. This was just as it was becoming clear in the nascent biotechnology industry that we would need these fragile cells for producing therapeutic antibodies. My doctoral research focused on improving the understanding, design, and operation of a packed cell bioreactor. This experience developed into what became a lifelong passion for R&D aimed at designing robust mammalian cell culture devices and processes, for reliable biomanufacturing.

Soon after arriving at UBC, this passion extended to stem cell biomanufacturing, collaborating with Connie Eaves and recruiting Peter Zandstra as our first co-supervised graduate student. Together we worked on improving methods for culturing stem cells, for example demonstrating that hematopoietic stem cells could successfully be cultured in homogeneous and scalable stirred suspension cultures as opposed to conventional static plates. We applied engineering design of experiment methods to optimize these complex cell processes. Likewise, I led a team that developed the first commercialized acoustic cell retention device that uses sound waves as a cell filter, a device that is now used for therapeutic protein manufacturing. Throughout my career, I’ve been driven by the challenge of translating cutting-edge science into practical, scalable, and cost-effective solutions.

2. What major challenges have you encountered during your research career?

One of the biggest challenges in this work has been the inherent complexity of biomanufacturing systems. Unlike basic science, we often cannot isolate individual variables to run simple, highly controlled experiments. In bioreactors for example, multiple variables are shifting simultaneously: nutrient levels drop, pH fluctuates, metabolites accumulate, and yet we need to generate results that are informative in the context of this dynamically changing environment. Navigating this complexity requires choosing appropriate compromises in order to generate informative results, while sometimes coping with ambiguous results. To address this, we rely heavily on multifactorial experimental designs, mathematical modeling, and careful control of the culture environment. For the latter, my lab recently acquired analytical equipment that, in just six minutes, simultaneously measures key culture levels of glucose, lactate, ammonium, pH, oxygen, osmolality, and cell concentrations. In any scientific cell culture experiments variations in these factors can confound results, so we encourage other labs to use this equipment to verify that their experimental designs are only investigating the variable of interest. Likewise, the quality of cultures used for cell inputs to experiments should be verified, most of all for very costly single cell experiments. 

Another challenge for bioprocess engineers is overcoming the perception among many biological scientists that biomanufacturing is best left to industry rather than academia. While industry has far more manufacturing experience, their workers do not typically have the time or resources to pursue the focused, in-depth research performed by academic engineers. This gives university-based biomanufacturing researchers great opportunities for transformative technological innovation.

Such potential was recognized early on by Michael Smith and Doug Kilburn as they designed the Biotechnology Laboratory, which became the Michael Smith Laboratories when it was renamed in 2004.  However, I doubt they anticipated that engineers would be the ones to deliver the most commercially successful spin-off company (to date). I was a key part of the team that developed the UBC microfluidic technology that led to the founding of AbCellera in Vancouver. Overall, five engineers from the Michael Smith Laboratories were central inventors, including Carl Hansen and Veronique Lecault, two of the company’s co-founders. AbCellera went on to win the global race to obtain the first FDA Emergency Use Authorization for a COVID-19 antibody treatment, saving tens of thousands of lives. Given the impact this innovation has had, support for engineering at the Michael Smith Laboratories and UBC remains a crucial advantage of ours. Biotechnology is fundamentally an applied science, with impacts that extend from improving health care to mitigating climate change and enhancing food security, all major challenges of the coming decades.

3. Are there any research topics in your field that you believe are currently undervalued? Where do you see these areas heading in the next 5–10 years?

One major focus of my work has been on process analytical technologies, particularly because cell therapy products are incredibly complex, and therefore can present unpredictable risks to their recipients. I believe that far more innovation is needed in this area to stay ahead of this challenge and allow the technology to reach its full potential. Toward that goal, I have invested a lot of time and effort in developing Raman microscopy as a process analytical technology. This has been made possible through the spectroscopy expertise of Robin Turner’s group. Together, we have developed a shared passion for advocating and demonstrating that Raman spectroscopy is needed to support more reliable cell therapy biomanufacturing.

Raman-based methods allow us to non-invasively monitor the overall composition of cells, providing information that complements conventional assays like mRNA profiling and flow cytometry. The ability to rapidly monitor and characterize cell populations in a more holistic, label-free manner is especially valuable in the context of quality control, a crucial capability for ensuring the safety and therapeutic effectiveness of these highly complex and promising biological products.

The future of this field will depend on the integration of such advanced analytical tools into scalable, routine workflows. Since serious adverse events can result in market entry delays of years, often with financially devastating consequences, robust quality monitoring technologies are a crucial component of both successful and sustained commercialization. I believe innovation in this area will grow rapidly over the next decade, a central component of the maturation of the cell therapy industry.

4. What advice would you offer to someone beginning their research career in your area?

My advice to researchers beginning their careers in biomanufacturing is to continuously develop their ability to ask good questions, and communicate effectively with both biological collaborators and broader audiences. Bridging engineering and biology is essential for navigating the complexity of modern biomanufacturing research, and doing so can lead to highly impactful translational outcomes that are only expected to accelerate in the coming years.

Additionally, high-quality applied science in a biological context requires access to biological scientists and their domain-specific expertise. Unlike many academic researchers in my field who work somewhat in isolation, I have had the privilege of collaborating with outstanding biological scientists such as Connie Eaves, Tim Kieffer, Jim Johnson, and Megan Levings. It is crucial for new researchers to seek and engage the right collaborators, scientists who not only excel in their fields but who also value the crucial contributions that academic engineers can make toward translating their high quality science into real world applications and impacts.