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School of Medicine receives $12 million NIH contract for new Cardiovascular Proteomics Center
By David J. Craig
After the Human Genome Project produced a virtual blueprint of the human body by identifying its approximately 30,000 genes, biomedical researchers began to closely examine the proteins encoded by those genes to do specific tasks. Proteomics -- the study of the structure and function of the human body’s some 200,000 proteins -- is one of today’s hottest areas of biomedical research, and it is the focus of an increasing number of studies at BU’s School of Medicine.
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| Peter O’Connor, a MED research assistant professor of biochemistry, Catherine Costello, a MED research professor of biochemistry, and Richard Cohen, a MED professor of medicine and pathology and director of the school’s Vascular Biology Unit (from left), will develop new technologies to study how proteins are involved in cardiovascular disease at BU’s new Cardiovascular Proteomics Center. Photo by Kalman Zabarsky |
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This month, MED received a $12 million, seven-year contract from the
National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes
of Health (NIH) to create the Cardiovascular Proteomics Center. As part
of the contract, about 50 researchers from 10 BU laboratories will participate
in projects that could yield new diagnostic tests and medications, and
other treatments for illnesses such as heart disease, arteriosclerosis,
and sickle cell anemia.
“Unraveling the complex functions of proteins offers the greatest
promise for improving the lives of millions of people,” says Aram
Chobanian, MED dean and BU Medical Campus provost. “The characterizing
of the human genome has provided us with new tools to explore human biology.
However, understanding the intricacies of body functions and disease processes
will ultimately depend on in-depth knowledge of proteins, most of which
are very poorly characterized, and which interact in a complex manner
to control cellular activity.”
The Cardiovascular Proteomics Center will develop new technologies and
conduct basic research on the effect of oxidant stress on proteins crucial
to the function of cardiovascular cells. Oxidant stress is the process
by which free radicals -- oxygen molecules that have either gained or
lost an electron -- steal an electron from a protein so that all of its
own are paired. The destruction to proteins caused by oxidant stress is
a basic part of aging and is believed to be hastened by factors such as
cigarette smoke, air pollutants, and sun exposure.
“It’s generally recognized that cardiovascular risk factors
such as cholesterol, diabetes, and smoking cause cardiovascular cells
to act abnormally, at least in part, by increasing oxidant stress,”
says Richard Cohen, a MED professor of medicine and pathology, director
of the school’s Vascular Biology Unit, and co–principal investigator
of the NHLBI contract. “But we want to know how certain proteins
are involved in that process, which is a key to understanding exactly
what’s happening to the cardiovascular cells.”
Researchers from several MED departments, as well as faculty at the College
of Arts and Sciences biology department and the College of Engineering
biomedical engineering department, will incorporate proteomic techniques
into their existing studies to better understand the cardiovascular damage
that occurs when proteins are oxidized by free radicals. Building on the
insights into cellular metabolism gained by genomics, they will study
the pathogenesis of cardiovascular diseases by examining how proteins
behave in cultured cells, in animals, and in humans.
Catherine Costello, a MED research professor of biochemistry, also will
serve as co–principal investigator of the NHLBI contract, overseeing
the development of new technologies for protein analysis. One group of
researchers at the center will develop a mass spectrometry instrument
that will enable quick analysis of complex protein mixtures. Mass spectrometers
are used to measure the mass of individual molecules or molecule fragments
and therefore can profile changes in proteins resulting from oxidant stress.
“Proteomics has become the killer application for mass spectrometers,
because proteomics generates sufficiently complex problems to justify
the high performance of the mass spectrometer,” says Peter O’Connor,
a MED research assistant professor of biochemistry and a spectrometry
expert. “A sample may have as many as 10,000 proteins, each of which
generates 10 to 20 peptides, so you have a mixture of a couple of hundred
thousand components. What I’m interested in doing is improving what
is now the highest resolution instrument out there, so it can analyze
many samples at once, in a high-throughput, automated motion.”
In addition, data from the ongoing 54-year-old Framingham Heart Study,
an NHLBI-funded project operated by BU, will be used to create new diagnostic
markers to help researchers and clinicians monitor chemical reactions
involving proteins that contribute to cardiovascular disease. “The
markers might be used to track how quickly vascular disease develops in
a patient who is a smoker, as opposed to another person, and to see how
his body stands up to the oxidant stress,” says Cohen.
The center will develop other technologies for analyzing proteins in collaboration
with Beyond Genomics, Inc., a Waltham, Mass., biopharmaceutical company
that specializes in proteomics, which has been hired as a subcontractor.
“Beyond Genomics has developed technologies for looking at complex
protein mixtures in mammalian tissues,” Cohen says, “and the
company is going to help us establish that technology at the core laboratory
we’re establishing for proteomics at BU.
“A provision of this NIH program,” he continues, “is
that information gained through the Cardiovascular Proteomics Center will
be rapidly disseminated, including via the Web, so that other research
programs might also benefit, and to ensure that our discoveries benefit
patient care as soon as possible.”
25 October 2002
Boston University
Office of University Relations