Microfluidics-based genomics analysis

Microfluidics technologies facilitate rapid, high-throughput, and reproducible capture and analysis of individual cells

Systems-level reconstruction of the disease state

Global gene expression analysis of individual cells comprising normal or cancer tissues facilitate reconstruction of how the system functions in toto

Stem cells in development and disease

Understanding the role of stem cells and developmental programs in cancer initiation and metastasis

We use diverse single-cell genomic and spatial technologies to study cellular heterogeneity and generate new insights into the basic cellular and molecular mechanisms that drive tissue homeostasis and metastasis.

Cells use different forms of metabolism depending on their bioenergetic needs and access to nutrients. We study the role of cellular metabolism in metastatic spread and why specific forms of metabolism are beneficial for metastasis.

We study how the immune system controls metastasis to the central nervous system (CNS), a particularly deadly form of metastasis. The CNS immune microenvironment is unique and its ability to control metastasis is poorly understood.

Tumors behave like normal tissues, which are hierarchically organized with stem cells that give rise to more differentiated progeny. We study how stem cells and their unique biological properties promote cancer progression and metastasis.

Featured publication

Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing
Davis RT et al., Nature Cell Biology, 2020

Although metastasis remains the cause of most cancer-related mortality, mechanisms governing seeding in distal tissues are poorly understood. Here, we establish a robust method for the identification of global transcriptomic changes in rare metastatic cells during seeding using single-cell RNA sequencing and patient-derived-xenograft models of breast cancer. We find that both primary tumours and micrometastases display transcriptional heterogeneity but micrometastases harbour a distinct transcriptome program conserved across patient-derived-xenograft models that is highly predictive of poor survival of patients. Pathway analysis revealed mitochondrial oxidative phosphorylation as the top pathway upregulated in micrometastases, in contrast to higher levels of glycolytic enzymes in primary tumour cells, which we corroborated by flow cytometric and metabolomic analyses. Pharmacological inhibition of oxidative phosphorylation dramatically attenuated metastatic seeding in the lungs, which demonstrates the functional importance of oxidative phosphorylation in metastasis and highlights its potential as a therapeutic target to prevent metastatic spread in patients with breast cancer.

 
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