microfluidics

Microfluidics-based genomics analysis

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

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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

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Stem cells in development and disease

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

 

Patient-derived xenograft (PDX) models are generated by transplanting human patient tumor samples into mice. Transplanted mice serve as patient ‘avatars’, which are the basis of our work because they are the most authentic model for studying human cancer.

The metastatic spread of tumor cells to other tissues in the body is the cause of nearly all patient mortality. Our work focuses on identifying new strategies to prevent or control metastasis, as we believe this is the most promising approach to improving patient outcomes

Tumors behave much like normal tissues, which are hierarchically organized with stem cells at the apex that give rise to more differentiated progeny. We study stem cells to understand how normal developmental processes go awry during tumorigenesis.

The fundamental unit of all tissues is the single cell. Most biological systems (e.g., gene expression, mutation, cell signaling, differentiation, proliferation, migration) can be best understood by looking at the single cell level.

Featured publication

Single-cell analysis reveals a stem cell program in human metastatic breast cancer cells
Lawson DA et al., Nature, 2015

We utilized single-cell gene expression technology to investigate differentiation changes in metastatic cells at different stages of the metastatic process. In mice engrafted with human patient breast cancers, we found that metastatic cells from low-burden (earlier stage) peripheral tissues expressed higher levels of stem cell, epithelial-to-mesenchymal transition (EMT), pro-survival, and dormancy-associated genes. In contrast, metastatic cells from high-burden (later stage) tissues were similar to primary tumor cells, which were more heterogeneous and expressed higher levels of luminal differentiation genes. Transplantation of stem-like metastatic cells from low-burden tissues showed that they have significant tumor-initiating capacity, and can differentiate to produce luminal-like cancer cells. These findings support a hierarchical model for metastasis, where metastases are initiated by stem-like cells that proliferate and differentiate to produce advanced metastatic disease.

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