EVMS microbiologist lands
$1.8 million NIH grant to study viral brain infection
May 1, 2007
 |
|
Edward M. Johnson, Ph.D. |
NORFOLK—Edward M. Johnson, Ph.D.,
professor and chairman of the Department of Microbiology and
Molecular Cell Biology, received a grant totaling more than $1.8
million over five years to study the molecular mechanics of a brain
disease that kills four percent of AIDS patients worldwide.
Johnson's research focuses on the JC
virus, discovered in 1971 and named for the initials of a patient
who died of progressive multifocal leukoencephalopathy, or PML, a
disease that kills patients by essentially causing their brain's
neurons to short-circuit. PML, which afflicts patients with a
weakened immune system, is aggressive and incurable. The time
between the onset of symptoms and death can be less than a few
months. The brain-wasting disease can occur even in patients whose
AIDS is kept in check by aggressive antiretroviral drugs. The JC
virus, the focus of Johnson's study, causes the brain to lose
myelin, the sheath that insulates the passage of nerve signals. Such
demyelination is also found in diseases such as multiple sclerosis.
William J. Wasilenko, Ph.D., associate
dean for research, said the grant from the National Institutes of
Health (NIH), the gold standard of medical research, reflects
Johnson's status as a national leader in studying the connection
between viruses and cancer.
"This research addresses a very
important yet poorly understood component of AIDS pathology," said
Wasilenko. "Dr. Johnson's research results have great potential to
lead to new clinical treatments for AIDS and many other viral
pathologies."
Johnson, who came to EVMS in 2005 from
The Rockefeller University, Memorial Sloan-Kettering Cancer Center
and Mount Sinai School of Medicine, has a long history of NIH
funding for his research on AIDS and cancer.
Johnson's research on the JC virus dates
back to the 1980s, when he started studying DNA replication of the
polyoma virus, whose variants include the JC virus. Present in more
than 90 percent of adults, the polyoma resides in the kidneys and
was once considered relatively benign, one of many viruses in humans
that cause no illnesses. Johnson's research showed that the normally
latent virus occasionally begins replicating wildly, and that this
is a major risk factor for cancerous tumors in the urinary tract.
While researchers knew that the polyoma
infections were present in cancer cells, demonstrating that the
virus played a role in causing cancer didn't occur until 2006 when
Johnson and a team of researchers examined the records of 3,785
patients and showed that those with polyoma infections were nearly
four times more likely to develop bladder cancer. Johnson's group is
now examining the connection to related cancers, including prostate
cancer.
Although researchers have known for
years that the JC virus caused the brain-wasting PML, nobody has
figured out exactly how. In fact, researchers don't understand how
the JC virus, or even the AIDS virus, gets into the brain through a
kind of microscopic cheesecloth that filters from the blood anything
that can harm the brain. Johnson speculates that the viruses may
infect cells that are able to squeeze through the protective
blood-brain barrier. "This remains an important problem to solve,"
Johnson said.
Johnson's newest five-year grant will
help him unravel the mystery of exactly how the JC virus does its
damage. While many have theorized that damaged immune systems of
AIDS patients leave them vulnerable to otherwise benign viruses,
Johnson, going a step further, believes that proteins produced by
the AIDS virus, HIV, may actually supercharge the JC virus. To do
this, the HIV proteins interact with proteins produced by cells in
the brain.
This prompts a molecular cascade that
kills brain cells called oligodendrocytes. These cells have long,
sticky tendrils that wrap around and insulate wire-like nerve fibers
that connect the brain's neurons. Without this insulation, myelin,
the brain's neurons misfire and then atrophy, leaving dead tissue
scattered through the brain.
Because brain tissues don't divide,
Johnson's must conduct his study using oligodendrocytes removed from
patients suffering from malignant brain cancer. Ironically, the
cancerous cells are taken from patients whose cancer kills by
causing massive overproduction of the cells that are destroyed in
patients with PML.
If Johnson can decipher the molecular
mechanics, the research could help doctors find a way to disrupt the
sequences of infection in both PML and AIDS and help stop these
diseases.
"The interaction of HIV with other
viruses is definitely a target for therapeutic agents," said Johnson.
Top
|
