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The Maley laboratory is exploring fundamental concepts in neoplastic progression, the processes by which normal tissue becomes cancerous, for the purposes of developing better methods for cancer prevention and therapy. They are applying evolutionary biology, ecology, computational biology and genetics to the understanding of these problems. We are interested in all aspects of evolution in cancer, including the evolution of cells within tumors and normal tissues (“somatic evolution“) as well as the selective effects of cancer on the evolution of multicellular organisms. We take three, mutually reinforcing, approaches to these problems:
Observational: Evolutionary analysis of the genetics from tumors
We analyze tissue samples from tumors, mainly Barrett’s esophagus and acute myeloid leukemia (AML), and apply evolutionary theory to the genetics and epigenetics of the samples. We are interested in understanding and controlling the dynamics of clonal diversity within those tumors.
Theoretical: Computational modeling of somatic evolution
We use agent-based models to represent the populations of cells in tumors and to track their evolution over time. These models help us explore the implications of current theories in cancer biology and to design experiments aimed at understanding and controlling somatic evolution.
Experimental: Evolutionary experiments in model systems
We use both yeast and human cell lines in tissue culture to study how we might control somatic evolution so as to prevent cancer and therapeutic resistance.
The Maley Lab will soon (~ January 2015) be hiring at least 4 post-docs or staff scientists to work on the evolutionary biology of cancer. Specific projects and desired expertise include:
Genomic diversity within cancers. There will likely be two positions available for analysis of high throughput sequencing data on multi-region samples to measure genetic diversity within breast cancers, AML, bladder cancers, and potentially others. The ideal candidate would have expertise in both evolutionary biology and high throughput sequence analysis. Background in single cell sequencing and/or the human microbiota would be favored.
Phylogenetics of cancer cells. A phylogeneticist to help develop methods to reconstruct the phylogenies of cell lineages from within neoplasms. This will require the development of new likelihood models and the integration of multi-modal data (e.g., point mutations and chromosomal alterations). Initial data will derive from SNP arrays and exome sequencing of Barrett’s esophagus tissue samples. Experience withe BEAST would be favored. We will work with Mary Kuhner on this project.
Mouse models of Peto’s Paradox. A genetic mouse modeller who will investigate cancer suppression using transgenic mice with genetic constructs inspired by Peto’s Paradox and the results of analyses of whales and elephants, in collaboration with Lou Chesler at the Institute for Cancer Research in London. We also seek to develop a mouse model of neoplastic progression that can be sampled longitudinally to study the effects of interventions on the somatic evolution of neoplastic progression.
Carlo Maley gave a public lecture at Arizona State University on “Why we get cancer and why it has been so hard to cure.”
Our favorite science radio show and podcast, Radio Lab from WNYC, had an episode on “famous tumors”. It includes an interview with Carlo Maley about the evolution of cancer.