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Maitreya Dunham: Varied Interests in Cancer

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Title: Assistant professor, University of Washington
Education: PhD, Stanford University, 2003
Recommended by: Mary-Claire King, University of Washington, Drew Endy, Stanford University

Maitreya Dunham's varied interests in genomics, evolution, and the latest technologies have led her to study genome evolution in yeast with an eye toward applying what she learns to determine how cancers and other diseases progress. To do this, Dunham is using experimental evolution — she allows a culture of yeast to adapt to a new environment in the lab over several months and then uses genomic methods to explore the evolved strains. "In our yeast cultures, some of the same mutational mechanisms are important as in cancer cells," Dunham says. "Changes in gene copy number turn out to be selective, which is a pattern seen very frequently in cancer cells."

The ability to watch evolution in action and see how organisms adapt to carefully controlled experiments is what draws Dunham to this particular area of research. "There's more biology to be learned out there, and yeast is a great system — I like the combination of the model eukaryote with the microbial lifestyle."

The technological aspects of this research also appeal to Dunham. New sequencing technologies are often tested on yeast before being adapted for more complex genomes: "It's been a fun field to be in because we get the fun toys first," she says.

But there are challenges. Finding the link between genotype and phenotype is still a problem for many researchers. "You can discover a mutation and you can say, 'We observed this mutation in a strain that was subjected to the following selection conditions,' but you still can't link that mutation to adaptation to that selection condition without doing an experiment," Dunham says. There's still much modeling work to be done to understand a gene's role in its network to understand how a single point mutation can change protein function in a meaningful way, she adds.

Papers of note

In September, Dunham and her collaborators published a paper in Cell identifying several aneuploidy-tolerating mutations. The group found aneuploid yeast strains with improved proliferative abilities; molecular characterization of them revealed strain-specific genetic alterations and mutations shared between different aneuploid strains.

And the Nobel goes to ...

Dunham would like to be able to understand how aneuploidy and copy-number variations affect cells. "Why do aneuploid cancer cells have a growth advantage while most aneuploidies are incompatible with human development?" she asks. Understanding the underlying basis for the large pleiotropic mutations and how they evolve in diseases could have a Nobel-worthy impact on human health, she says.

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