Long Nguyen

At A Glance

• Our lab is interested in understanding the mechanisms that regulate cancer stem cell activity in human breast cancer, how these contribute to disease progression, relapse, and treatment resistance with the goal of designing new effective treatment strategies.
• We have considerable expertise in combining advanced clonal tracking systems with single cell analysis platforms to link phenotype, genotype, and function at clonal and single cell resolution in models of human cancer.
• We use primary patient material, and models of human breast cancer including patient-derived tumour xenografts, patient-derived tumour organoids, and human cancer cell lines.

Short Bio

Dr. Nguyen completed his MD/PhD in Experimental Medicine at the University of British Columbia with Dr. Connie Eaves on the topic of normal and malignant mammary stem cell biology. He trained in Internal Medicine and specialized in Medical Oncology at the University of Toronto. He then pursued a clinical/research postdoctoral fellowship in functional breast cancer genomics with Dr. Carlos Caldas at the University of Cambridge in the United Kingdom for which he received both a Translational Research Fellowship from the European Society for Medical Oncology, and a Young Investigator Award from the American Society of Clinical Oncology.

Dr. Nguyen is a Scientist, and a Staff Medical Oncologist in the Breast Site Group at Princess Margaret Cancer Centre. He is an Assistant Professor in the Department of Medicine, and in the Department of Medical Biophysics. His research laboratory is focused on studying clonal heterogeneity in human breast cancer to understand how rare malignant clones contribute to disease progression and treatment resistance.

Research Synopsis  

The expertise of our lab is in studying tumour heterogeneity from a phenotypic, genomic, and functional perspective by combining advanced clonal tracking systems such as expressed lentiviral-based cellular barcoding with single cell sequencing platforms to understand the relationship between phenotype, genotype and function of malignant tumour cells. We apply these methods in a robustly quantitative manner to study cancer stem cell biology on a clonal level and at single cell resolution.

We are interested in the molecular mechanisms which govern clonal fitness and long-term regenerative activity with the aim of identifying which malignant cell types within a tumour are ultimately responsible for disease progression. Furthermore, we are probing the mechanisms which allow these clones to resist treatment to identify genetic susceptibilities which can be used to overcome treatment resistance.

For our work, we use primary patient material or models derived from these materials, such as patient-derived tumour xenografts, or patient-derived tumour organoids, to study the disease as close as possible to that of the patient. We work closely with a strong network of collaborators both nationally and internationally.

Recent Publications

1. Nguyen LV, Caldas C. Functional genomics approaches to improve pre-clinical drug screening and biomarker discovery. EMBO Molecular Medicine 2021, PMID: 34254730.
2. Nguyen LV, Searle K, Jerzak KJ. Central nervous system-specific efficacy of CDK4/6 inhibitors in randomized controlled trials for metastatic breast cancer. Oncotarget 2019, PMID: 31695840.
3. Lan X, Jorg D, Cavalli FMG, Richards LM, Nguyen LV, Vanner R, Guilhamon P, Lee L, Kushida MM, Pellacani D, Park NI, Coutinho FJ, Whetsone H, Selvadurai HJ, Che C, Luu B, Carles A, Moksa M, Rastegar N, Head R, Dolma S, Prinos P, Cusimano MD, Das S, Bernstein M, Arrowsmith CH, Mingall AJ, Moore RA, Ma Y, Gallo M, Lupien M, Pugh TJ, Taylor MD, Hirst M, Eaves CJ, Simons BD, Dirks PB. Fate mapping of glioblastoma reveals an invariant stem cell hierarchy. Nature 2017, PMID: 28854171.
4. Balani S, Nguyen LV, Eaves CJ. Modeling the process of human tumorigenesis. Nature Communications2017, PMID: 28541307.
5. Nguyen LV, Pellacani D, Lefort S, Kannan N, Osako T, Makarem M, Cox CL, Kennedy W, Beer P, Carles A, Moksa M, Bilenky M, Balani S, Babovic S, Sun I, Rosin M, Aparicio S, Hirst M, Eaves CJ. Barcoding reveals complex clonal dynamics of de novo transformed human mammary cells. Nature 2015, PMID: 26633636.
6. Eirew P, Steif A, Khattra J, Ha G, Yap D, Farahani H, Gelmon K, Chia S, Mar C, Wan A, Shumansky K, Rosner J, McPherson A, Nielsen C, Roth AJL, Lefebvre C, Bashashati A, deSouza C, Siu C, Edwards J, Oloumi A, Osako T, Bruna A, Sandoval J, Algara T, Greenwood W, Leung K, Cheng H, Xue H, Wang Y, Lin D, Mungall A, Moore R, Zhao Y, Lorette J, Nguyen L, Huntsman D, Eaves C, Hansen C, Marra M, Caldas C, Shah SP, Aparicio S. Dynamics of genomic clonal evolution in breast cancer patient xenografts at single cell resolution. Nature 2015, PMID: 25470049.
7. Nguyen LV, Cox CL, Pellacani D, Eirew P, Kannan N, Carles A, Moksa M, Hirst M, Aparicio S, Eaves CJ. DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts. Nature Communications 2014, PMID: 25532760.
8. Nguyen LV, Makarem M, Carles A, Moksa M, Kannan N, Pandoh P, Eirew P, Osako T, Kardel M, Cheung AM, Kennedy W, Tse K, Zeng T, Zhao Y, Humphries RK, Aparicio S, Eaves, CJ, Hirst M. Clonal analysis via barcoding reveals diverse growth and differentiation of transplanted mouse and human mammary stem cells. Cell Stem Cell 2014, PMID: 24440600.
9. Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nature Reviews Cancer 2012, PMID: 22237392.