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Yardena Samuels
Title: Head, Molecular Cancer Genetics Section, NHGRI
Education: PhD, Ludwig Institute for Cancer Research, 2002
Recommended by: Chris Austin, Elaine Ostrander

Melanoma is rare and deadly. It accounts for 75 percent of skin cancer-related deaths — and melanoma deaths often occur within six months of diagnosis. That's where Yardena Samuels has set her sights. "There's actually few therapeutic options for this disease," Samuels says. She's set out to uncover the genetics of melanoma and translate those findings into the clinic to help patients. "I'm a strong believer that understanding the genetics of cancer can lead to personalized medicine," she says.

While she has the cancer genetics expertise — Samuels did a postdoc in Bert Vogelstein's lab at Johns Hopkins — Samuels collaborates with Steven Rosenberg, who, as chief of surgery at the National Cancer Institute, falls squarely in the clinic. She receives samples from Rosenberg that she analyzes at the bench, passing her findings back to Rosenberg's clinic. "We have this really good cycle where we complement each other, me doing the genetics and functional work and then him actually being able to treat patients," she says.

For one part of her research, Samuels is focusing on signal transduction pathways. Her lab has sequenced all the matrix metalloproteinase and tyrosine kinase genes. "Now, we want to complete more gene families that are involved in signal transduction because these are amenable to inhibition, and we want to be translational," she says. In addition to the genetic work, Samuels is targeting the most highly mutated genes from those families for functional analysis. From that, her group will create a database of mutations. "We hope that that database will give us an understanding of pathways disturbed in melanoma and that will tell us which ones can be inhibited," she says.

Samuels is also sequencing the whole genomes of melanoma samples. One tumor is just about done — she says it looks promising — and she plans to sequence at least 10 more.

Looking ahead

According to Samuels, the future holds a lot of functional analysis. With more whole-genome sequencing catching on, there will be a flood of data, she says. "We're going to have a lot of complementary approaches to finally see the spectrum of these genetic alterations because we'll be able to see all single base changes as well as amplifications, deletions, translocations, epigenetic changes, and transcriptional changes — all at once," she says. That will let researchers pinpoint what genes are the most important in different types of cancers.

However, all that functional work also poses a challenge. "That takes much more time because there are so many of these that are passenger mutations," Samuels says. "It's difficult to decide what's a passenger or a driver mutation. Statistics are just not enough; we really need to find a way to look at this functionally."

Publications of note

In an October Nature Genetics paper, Samuels and her colleagues describe a mutational analysis approach to studying the tyrosine kinase gene family in melanoma. "We take into account what's already known in the literature about that pathway. Then, we use normal biological approaches where we overexpress the wild-type and mutation forms and look at activation of that pathway," she says. They found that the ERBB4 gene was mutated in nearly 20 percent of melanomas and, if those mutated cells were treated with lapatinib or shRNA-mediated knockdown, there was reduced cell growth. Based on those findings, Samuels and her colleagues are planning a clinical study.

And the Nobel goes to...

Samuels would like to win the Nobel for "making a significant contribution to the understanding of cancer that would lead to the development of effective treatments."

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