Physiology and Biophysics, UC Irvine
Devon A. Lawson
About UCI
A new window into metastasis
Using single-cell technologies to reveal the fundamental underlying properties of individual metastasizing cells
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
Patient-derived xenograft (PDX) models are generated by transplanting human patient tumor samples into mice. PDX mice can subsequently serve as patient 'avatars' to authentically study many aspects of tumor progression and metastasis.
The metastatic spread of tumor cells to other tissues in the body is the cause of nearly all mortality for breast cancer patients. 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-like cells at the apex that give rise to more differentiated progeny. We study the role of stem cells and cellular differentiation in cancer progression and metastasis using in vitro, in vivo, and genomic approaches.
Single cell genomics
The fundamental unit of all tissues is the single cell. We use diverse single-cell technologies and bioinformatic approaches to understand cellular diversity and its impact on cancer progression and metastasis.
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.
The Lawson lab is interested in understanding the cellular and molecular mechanisms underlying the metastatic spread of cancer cells to peripheral tissues. We take a systems-level approach, using cutting edge single-cell technologies to understand how the interplay between intracellular signals within the cancer cells, and extracellular stimuli from cells in the microenvironment influence the metastatic potential of individual cancer cells. We believe that new insights into the metastatic process will lead to new drugs to prevent and treat metastatic disease.
140 Sprague Hall
Chao Family Comprehensive Cancer Center
The University of California, at Irvine
Email: dalawson@uci.edu
Study reveals seeds of Metastasis: Comment on Lawson DA et al., Nature, 2015
What we're reading:
Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance (Fischer et al., Nature, 2015)
DNA barcoding reveals diverse growth kinetics of human breast tumour subclones in serially passaged xenografts (Nguyen et al., Nature, 2015)
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