At the Princess Margaret Cancer Centre, University Health Network
The mission of our lab is to redefine translational cancer research by identifying novel treatment strategies that disrupt malignant clone function. To achieve this, we are actively investigating the molecular programs that regulate specific clone functions such as propagating activity, metastatic activity and treatment resistance. This will aid in our efforts to devise targeted treatment strategies to disrupt the function of these clones that are responsible for disease progression.
Sarah received a Travel Grant to attend the 2025 EACR Congress in Lisbon to present her work on “Dynamics and chemotherapy response of single cell-derived human breast cancer clones” on June 18, 2025 in the Joint EACR-ASPIC Symposium on Cancer Therapy Resistance. Her oral presentation was very well received – well done, Sarah!
This work was supported by the Princess Margaret Cancer Foundation, Canadian Cancer Society, and Marathron of Hope Cancer Centres Network/Terry Fox Research Institute.
The latest publication from the Nguyen, Caldas and Rueda labs. This was a massive effort from a fantastic team and we’re grateful to everyone on the paper for their work on this project! https://doi.org/10.1016/j.celrep.2025.115699
In this paper we used expressed lentiviral barcoding to track the clonal growth of over 20,000 single-cell-derived clones in 110 xenografts from 26 patient-derived breast cancer xenograft models. We also profiled 167,375 single-cell RNA profiles to link clonal growth with gene expression.
We show that extremely rare cells can give rise to clones with propagating activity (frequency 1 in 15,000 – 1 in 116,000). Dominant propagating clones regenerate the full model-specific transcriptional landscape and there is a conserved differentiation program.
In vivo clone doubling time, a metric used to quantify the rate of clonal growth, reveals breast cancer subtype-specific differences in clonal fitness.
Dichotomous cell populations in basal breast cancer distinguish between functional clone types based on differential signaling and metabolic responses. This suggests it is possible to enrich for cells with propagating activity.
Dominant propagating clones display dynamic transcriptional plasticity which we illustrate by profiling gene expression across generations of cells derived from single starting cells.
Altogether, we illustrate the dynamic nature of transcriptional plasticity in propagating clones, highlighting their ability to evolve, adapt, and mature into dominant clones that constitute the majority of tumor cells in secondary xenografts, all originating from a single barcoded cell.
We welcomed Dr. Sahil Sharma as the newest addition to the Nguyen lab with our first lab retreat!
Dr. Sharma comes to us after completing a PhD in Experimental Medicine at McGill University with expertise in cell signaling, molecular biology and RNA biology. His postdoctoral project will focus on developing functional genomics approaches with CRISPR applied to organoid and xenograft models to investigate the molecular regulation of malignant clone function in human breast cancer.
Congratulations to Sarah on this award for her project “Identifying cells inside breast tumours which drive chemotherapy resistance”. With funding from the Canadian Cancer Society, Sarah is researching why some cells within breast tumours respond differently to chemotherapies. If successful, this project could lead to new ways of targeting breast cancer cells that are resistant to chemotherapy, improving outcomes for people with breast cancer.
Heejin Hayley Shin is a PhD student in the Nguyen lab who was awarded the MBP Excellence UTF scholarship. This is funded by an endowment created by Ontario Cancer Institute/Princess Margaret Cancer Centre, the Province of Ontario and the University of Toronto. Congratulations Hayley, way to go!