For Release: November 19, 2009
Contact:
David Corriveau, Media Relations Officer, Dartmouth Medical School, at David.A.Corriveau@Dartmouth.edu or 603-653-0771
Mark Hollmer, Media Relations Officer, Brown University, at mark_hollmer@brown.edu or 401-863-2476
DMS researchers to join $6m NIH study
Dale Mierke, Ph.D.
Mark Spaller, Ph.D.
Dartmouth Medical School's Dale F. Mierke, Ph.D., will collaborate with researchers from Brown University and Germany's University of Tuebingen on a five-year, $6-million study aiming to learn how a virus that can trigger a rare brain disease attaches to host cells.
With a grant from the National Institutes of Health (NIH), Brown professor Walter Atwood, Ph.D., is leading the study of progressive multifocal leukoencephalopathy (PML), which occurs in patients with compromised immune systems, such as those who suffer from HIV and AIDS. The condition, almost always fatal, is increasingly afflicting some multiple-sclerosis patients and others with autoimmune disorders who are undergoing treatment with drugs that suppress the immune system.
Mierke, a member of DMS's biochemistry faculty and a professor of chemistry at Dartmouth College, will focus his research on the virus that causes PML, with more than $2.4 million of the NIH grant. Mark R. Spaller, Ph.D., an associate professor of pharmacology and toxicology at DMS and a member of the Molecular Therapeutics Research Program at Norris Cotton Cancer Center (NCCC), will provide technical support in chemical/molecular libraries, and co-direct the synthetic core.
Mierke came to Dartmouth in 2007 from Brown Medical School, where his laboratory had collaborated with Atwood's since 2004.
"Our group used molecular modeling techniques to provide a structure framework for analysis of mutational data carried out by the Atwood group, investigating the initial binding of the virus to the host cell," Mierke says. "Based on these findings and protein engineering, we developed a soluble protein template. ... [With the new NIH funding, the researchers will use that template to] screen peptide and chemical libraries to identify molecules that bind to our virus mimic, thereby developing inhibitors of further spread of the virus."
Earlier research by Atwood and others found the cells to which the so-called JC virus - named for John Cunningham, the first patient in whom scientists isolated it in 1971 - sticks, and identified which receptors are involved. The process involves a complex of carbohydrate molecules with a protein in the central nervous system. One of the serotonin receptors in the carbohydrate complex serves to attach the virus to the cells. The new grant will seek details about how the virus gains traction in the brain.
While researchers estimate that more than 70 percent of the human population has been exposed to the virus, it only causes disease in some immunosuppressed patients. These include a small number with cancers such as non-Hodgkins lymphoma, and some with AIDS.
In recent years, some antibody-based therapies for autoimmune diseases such as multiple sclerosis and Crohn's disease have left some patients vulnerable to PML.
The virus, which Atwood first began studying in 1991 as a postdoctoral fellow at the NIH, is considered challenging because it has no animal model, which makes it difficult to test the effectiveness of therapies.