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Dr. Nika Shakiba, University of British Columbia
Scholar Award, $450,000 over 5 years (co-funded through a partnership between Michael Smith Health Research BC and Parkinson Society BC)
Project description:
Dr. Nika Shakiba from the University of British Columbia (UBC) is studying human pluripotent stem cells (hPSCs) and their applications for conditions like Parkinson’s disease (PD). hPSCs have the special ability to “expand” – make copies of themselves – and give rise to all cell types of the body. Since their discovery over 20 years ago, hPSCs have opened the door to producing cell therapies by transplanting lab-grown cells into the body to restore damaged function.
As a result, hPSCs have received excitement as a substrate to generate cell therapies for degenerative diseases and to replace damaged tissues on-demand. For example, ongoing clinical trials around the world are producing dopaminergic neurons from hPSCs to transplant into patients with PD. Results have shown promise, though further trials are needed. With these clinical trials already underway, clinical demand for hPSCs is growing.
To meet this demand and produce the large quantities of cells needed to treat Canadians, robust biomanufacturing approaches for producing trillions of hPSCs are required, a process called “hPSC expansion”. Canada’s booming biotechnology sector is strategically positioned to meet this demand. However, current hPSC expansion strategies experience challenges, because lab-grown hPSCs can acquire DNA mutations that make them cancer-like, making these cell batches unsafe for clinical use.
Indeed, like all cells in multicellular populations, hPSCs interact with their neighbours, and differences in the “fitness” of these cells leads fitter cells to out-compete and eliminate their weaker neighbours. hPSCs with cancer-like mutations can eliminate their normal neighbours. Further, “hPSC differentiation” strategies that convert hPSCs into therapeutic cell types (such as neurons) experience bottlenecks in their efficiency and yield, because of the loss of cells that are unable to survive in culture, as well as those that give rise to undesired cell types.
Dr. Shakiba’s laboratory at UBC specializes in applying genetic engineering and computational tools to uncover the underlying rules that govern hPSC expansion and differentiation, using this knowledge to create strategies for the production of cell therapies that are safe and cost-effective. Leveraging these tools, her lab works on detecting and removing cancer-like cells in hPSC expansion.
Preliminary results suggest that researchers may be able to predict when hPSCs are going bad in biomanufactured cell batches earlier than they could before, allowing them to intervene to preserve these batches. Using cutting-edge genetic tools to “barcode” and track hPSCs in culture, her team makes high-resolution measurements of the growth of each individual hPSC. Using computational models, her team can identify cancer-like cells based on their growth properties, regardless of the genetic changes they carry. To preserve the safety of costly hPSC batches, her team is now working collaboratively to improve the design of biomanufacturing platforms in which these cell batches are grown, reducing their risk of going bad. She is also working on developing new genetic tools to remove undesirable cells from batches.
Concurrently, her lab is studying hPSCs during differentiation to specialized cells (like neurons), identifying those that survive and thrive, as well as those that are lost. By genetically programming hPSCs, they seek to optimize the yield and efficiency with which specialized cells can be produced in the lab, overcoming bottlenecks to make hPSC-derived cell therapies economical and reliable.
The results of this research aim to build on the legacy of Canadian stem cell excellence that began with Drs. Till and McCulloch’s discovery in 1961, pushing hPSC-derived cell therapies closer to broad clinical use. Dr. Shakiba’s research program is also providing an interdisciplinary training environment, mobilizing the next generation of engineering scientists to build on the Canadian legacy of stem cell research, leading to health and economic benefits for Canadians.
Dr. Shakiba is a biomedical engineer who trained at the University of Toronto and MIT. As an engineer, she is fascinated by the idea of turning cells into fundamentally engineerable units of life by using the latest DNA tools to control their behaviour. She is motivated to make the manufacturing and manipulation of these cells robust so that we can develop cellular therapies to treat degenerative diseases like Parkinson’s.
She is also a big believer in outreach and mentorship. Beyond her research and teaching, she is passionate about providing equity in mentorship in scientific training through her latest project, Advice to a Scientist (https://advicetoascientist.com).