 The White House annually evaluates the nation's young scientists and engineers, looking to honor those with the greatest promise. The leaders receive the Presidential Early Career Award for Scientists and Engineers, or PCAS. Each year they look at individuals across the country who are supported by different agencies of the federal government, in particular scientists and engineers, and find those that exemplify creativity, accomplishment, outreach, leadership, and other positive attributes, and they select a very small subset. This year there were 12 that were selected who were supported by the National Institutes of Health, 10 are supported through grants from the National Institutes of Health, and two work here on the Bethesda campus within the intramural program. We're very fortunate that the two intramural scientists that win 2007 PCAS awards are both here in the National Human Genome Research Institute. The Genome Institute winners are Dr. Elliot Margolies, head of the Genome Informatics Section in the Genome Technology Branch, and Dr. Daphne Bell, head of the Reproductive Cancer Genetics Section in the Cancer Genetics Branch. The 2007 PCAS awards were just announced in December 2008, and in this information-intense world, the young winners learned about it in a fairly casual way. He actually informed me by email. No, and I usually get other types of emails from Michael, Goddusman, related to parking or, you know, the holiday schedule and so forth, but seeing this email was like late on a Friday, and it was actually addressed to me, I was high Elliot, and so that was like, oh, wait a second, this is something a little bit different. To be a recipient of the PCAS award is extremely prestigious, and I'm very honored to have been selected. You get it for having potential as a young scientist in the field of science or engineering. And it's basically to recognize those scientists and engineers that are really quickly rising stars, if you will. And certainly the two individuals here at NHGRI that are this year awardees fit that category well. We know frighteningly little about our genome sequence. A lot of people have heard about things called genes, which code for proteins, but it turns out this only makes up about one or two percent of the three billion bases in our genome. And trying to figure out what the rest of the 98 percent does in a nutshell is what my research program is all about. Certainly that two percent is very important. It's about 20 or so thousand genes, but we've got to turn them on and off at the right place at the right time. So these things we call them enhancers to turn on genes or silencers to turn off genes. And understanding that language, what encodes an enhancer, what's the specific order of A's, C's, G's and T's that would encode that is something we don't quite understand yet. One of the ways that my lab tries to tackle this question is through comparing our genome to that of other species' genomes, effectively using the experiments of evolution over the last millions and millions of years to try and tease out those places in the genome that we think are important or do something, we call those functional regions. And that's been a very helpful tool to find other places in the genome besides those places that code for genes that might be important because we don't really have to know how something is encoded to be functional, but we can tease out that evolutionary signature that says, you know what, this is a region that hasn't changed across millions and millions of years, so it must be important. In addition to understanding how the genome works, the team Dr. Margolies leads also develops new research tools. The other half of my lab is involved in using new sequencing technologies to address current challenges in genomics research. And over the last few years, we've seen a phenomenal explosion in the amount of sequence somebody in the lab can generate on a daily basis, both with cost and time so we can generate a lot more sequence, a lot faster, and a lot cheaper. Cheaper and faster sequencers can speed up the search for the genetic roots of a disease. When you're attacking a complex disease, there are kind of two approaches that you can take. You can analyze somebody's entire genome and do that for a few people and try and narrow down regions of the genome that are important. But the other way, once you've narrowed down certain regions that you think are important, whether they're genes or an entire genomic loci, parts of chromosomes, then what really becomes powerful is sequencing that part of the genome in many, many, many people. And that, there's always going to be a need for that because as we're finding, you know, people's DNA is more different than we might expect. Cancer is a genetic disease, making it an ideal candidate for these kinds of studies. My lab is trying to understand the genetic changes that actually lead to the development of a particular type of cancer known as endometrial cancer. Endometrial cancer is a tumor that arises within the lining of the uterus, or the womb, and affects about 32,000 women annually in the U.S. Most women present at an early stage in their disease, and their disease is actually still confined to the uterus, and by having a hysterectomy, they essentially have a cure. But about 15% of women have aggressive tumors, and what we mean by that is the tumor has already spread beyond the uterus by the time they're presented to a physician to give a sense of the importance of endometrial cancer. About 7,500 women die from endometrial cancer each year just in the U.S. alone. The major technique that we're using to unravel the genetic alterations in endometrial cancer is DNA sequencing, where we can read the sequence of genes that we think might be likely to cause the cancer in DNA from the patient's tumor, and compare that sequence with the DNA from a normal piece of tissue from the same patient, and we look for the differences to tell us which part of the sequences has been altered in the tumor. At the moment, we're looking at close to 200 different genes in the tumor set that we have. Dr. Bell's group is not just focusing on individual mutations, but on the biochemical pathways that control growth of individual cells. Understanding these pathways could have an impact on many different types of tumors. From our understanding of cancer genetics as a whole, we understand that it's really the pathway that's important to be destroyed or disrupted, and tumors can actually disrupt the pathway by either knocking out genes at certain parts along its length, and so based on that information, you can select pretty good candidate genes. Obviously, there will be genes and pathways that you'll miss, but it's a pretty good starting point. Understanding the genetic changes in these cancer-promoting pathways should lead to new ways of diagnosing the disease, and hopefully even to the development of new treatments. These are two individuals that came into NHGRI after international searches. We brought them here recognizing that they were stars, but it's gratifying to see that other people recognize them as exemplary scientists as well.