Earlier detection
How cells make “decisions” Archana Dhasarathy and Sergei Nechaev, assistant professors of biomedical sciences/Epigenetics Center of Biomedical Research Excellence Disease processes like cancer sometimes start because of faulty switching — just like a bad switch in your house can lead to all sorts of electrical problems. For molecular biologists and research collaborators (and marriage partners) Archana Dhasarathy and Sergei Nechaev, that entails searching for clues in the body’s gene expression system. All of that, of course, done at the molecular level, where you can’t really see directly what’s going on, they note. “We’re looking at the basic mechanism of how cells are programmed epigenetically into different fates,” said Nechaev. A long-standing question in biology has been how cells that have the same genes, or genome, can look so different, for
instance, and how cells containing the same set of genes can become muscle cells or brain cells. This implies mechanisms that go beyond the DNA or genetics — something called epigenetics. “It all starts with genes, which are pretty much the same in all cells in our body, but the information can be read completely differently in different cell types,” Nechaev said. “We’re trying to see how cells know which set of genes to activate. It’s not necessarily about genes themselves; it’s about which sets of genes and patterns of genes are active in each cell type.” The problem here — and it’s a very big problem — is how do cells know which pattern of genes to activate? “The key question in this age of genomics will be to understand how different cell types concurrently regulate these sets of genes,” Dhasarathy said. “Loss of the precise control over gene regulation can lead to improper choices, which could lead to cancer (and other diseases).” Dealing with a large amount of information at once is challenging, and therefore, Dhasarathy and Nechaev’s work — like that of many of their colleagues across campus — is largely collaborative. It involves experts in a variety of fields such as bioinformatics and systems biology. n
Looking for signals Donald Sens, professor of pathology Donald Sens completed his postdoctoral fellowship in molecular biology at Harvard Medical School. Since then, he’s been looking to identify biomarkers, or flags, that could reveal the presence of disease. In his case, he’s looking specifically for biomarkers for bladder cancer. “What I do in my research is look for biomarkers of disease progression,” said Sens, who’s the lead researcher on a $16.8 million federal IDeA Network of Biomedical Research Excellence (INBRE) grant. It is the largest single grant received by a UND researcher, and the third INBRE grant Sens has received. “The public wants a biomarker that tells them they don’t need to be treated, he says, “but biomarkers that say you don’t need treatment are hard to come by.” Part of the INBRE money that Sens administers is dedicated to a program in medical informatics, which encourages researchers to use Sens medical or clinical information on patients or people at risk for disease in relation to a health outcome. This might include pilot studies of mediPAGE 8
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Sergei Nechaev (left) and Archana Dhasarathy are among a group of scientists working to build a center for epigenomics and epigenetics research at UND. Photo by Jackie Lorentz.
cal records and disease risk or use of surveillance data from disease registries to test a defined hypothesis. In the area of research with which Sens is involved, the biomarkers he’s looking for are finicky to define — but that’s why he’s chasing them down. “It takes a lot of cells for a pathologist to see them,” Sens said. “We’re actually trying to get a handle on any protein that gives a signal on any cancer, not just bladder cancer.”
Something to crow about
But, Sens says, medical science hasn’t done much to crow about its successes. “The thing that has amazed me with diagnostics is that we’ve done a terrible job of taking victory laps,” he observed. “Consider the blood pressure device. It used to be that mercury thing hanging on the wall. It was quite an operation to access the blood pressure monitors in those days. Today, you can go into any drugstore, stick your arm in, and get your blood pressure taken for free. You can buy a little $25 meter. So it’s become easy to diagnose — and treat — high blood pressure. That’s saved a lot of lives.” “So we’ve already got a lot of earlier detection examples that go unappreciated,” Sens said. “Think of heart disease, where we can now easily prevent it from getting worse, or the pap smear that has made many women’s cancers totally preventable.” n