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Each year, The Pew Charitable Trusts chooses 20 of America's most promising new researchers as Pew Scholars in the Biomedical Sciences. The grants support new investigators poised on the edge of biomedical discoveries. Since 1985, the organization has provided more than $91 million to scholars who are junior faculty members at medical schools and research institutions across the United States.
Two Seattle Pew Scholars are using advances in genetics, such as gene mapping and microarray analysis, to investigate the causes of cancer. Dr. Michael Lagunoff, assistant professor of microbiology and adjunct assistant professor of immunology, is studying the molecular virology of Kaposi's sarcoma. This cancer causes tumors in AIDS patients and other susceptible populations. Dr. Nina Salama, affiliate professor of microbiology and investigator at Fred Hutchinson Cancer Research Center's division of human biology, is researching Helicobacter pylori, a bacterium associated with stomach ulcers and gastric cancer.
The two scientists face some similar challenges. The virus that causes Kaposi's sarcoma and the Helicobacter pylori bacterium can cause serious diseases, such as cancer in some infected patients, while leaving other infected individuals with no symptoms of illness. Each infection is more prevalent in specific regions of the world. Both infections cause suffering in developing countries where treatment is not readily available.
Kaposi's sarcoma is the leading cause of malignancies in AIDS patients in the United States, and the most common cause of tumors in parts of central Africa, where not all of those with the sarcoma have the AIDS virus.
A herpes virus known as KSHV was discovered in 1994 and found to be associated with all Kaposi's sarcoma tumors. KSHV is found in one to five percent of the United States population. In some parts of the world where Kaposi's sarcoma is more prevalent, such as in Sicily and southern Italy, approximately 25 to 30 percent of the population has KSHV.
The discovery of KSHV opened paths to cancer research. Using microarray analysis, Lagunoff is looking at how KSHV alters the gene expression of infected endothelial cells, and thereby causes the cells to grow out of control and become tumors.
Lagunoff also is studying how cytokines, agents that are released from cells and that can act on other cells, may play a role in tumor formation. This avenue of exploration is of interest because KSHV seems to be necessary, but not sufficient, for tumor formation. Many people who have KSHV do not develop tumors.
"HIV doesn't actually kill," said Lagunoff. "By destroying the patient's immune system, HIV allows opportunistic infections like KSHV to take hold and cause death. In the absence of a cure for AIDS, we need to find ways to control these opportunistic viruses that are killing patients."
Unlike KSHV, Helicobacter pylori infections eliminated through intervention with anti-microbial drugs. However, without treatment, the bacteria can cause gastric ulcers and cancer.
According to Salama, physicians and researchers believed for a long time that the stomach was a sterile environment. While acids and the vigorous turnover of stomach contents make it a restrictive environment, Helicobacter pylori lives in the stomach lining in many genetic variations. These variations occur not only in different patients, but also within a single patient. Salama hopes to describe this variability, as well as its impact in determining whether a patient actually will develop stomach ulcers or cancer.
Salama is using two approaches to identify genes that are required for Helicobacter pylori to establish an infection in the hostile environment of the human stomach. One approach is microarray analysis of the bacteria's genetic variations. The other is a high throughput method of testing bacterial mutants in mice.
According to Salama, human genetic risk factors and environmental factors also likely influence whether an infected person will go on to have diseases related to Helicobacter pylori.
Said Salama, "Our goal is to understand Helicobacter pylori better so that we can devise better therapies. Because the infection is so common, it may not make sense to treat everybody. We need to be able to identify those individuals who are most likely to progress to severe disease."
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