Dr. Samie Jaffrey Receives Competitive NIH Director's T-R01
Award
Speedier Lab Testing With Results That Glow in the Dark
Dr. Samie Jaffrey, associate professor of pharmacology at Weill
Cornell Medical College, is among the first researchers to win a
prestigious NIH Director's Transformative R01 award from the
National Institutes of Health. Dr. Jaffrey and his colleagues are
developing innovative protein recognition technologies that may
some day speed up lab testing by instantaneously measuring proteins
within biological samples.
Protein detection is essential for diagnosing illnesses,
detecting environmental toxins, and for most types of biomedical
research. Protein detection typically takes hours or days, and
requires antibodies that specifically bind these proteins.
Specialized techniques are required to transform the binding of
these antibodies into signals that detect the presence of these
proteins. Dr. Jaffrey and his lab are developing new protein
recognition tools that rapidly emit light upon binding specific
target proteins. These simplified protein sensors have the
potential to vastly simplify and reduce the expense of protein
detection.
Dr. Jaffrey has been developing sensors from RNA, a natural
bio-molecule that has the capacity to adopt a variety of shapes. By
designing these molecules that are complementary to proteins, RNA
can form complexes with specific target proteins. The RNAs are
designed to bind fluorescent compounds after forming complexes with
proteins. If the RNA binds to the complementary target protein in a
urine, blood, or tissue sample, the sample glows green, which
indicates a positive presence of the targeted protein.
"The ability to simply add a sensor to a biological sample, and
monitor the level of a given protein in minutes, would allow
clinical diagnosis and medical decision making to occur much more
rapidly," explains Dr. Jaffrey. "A big advantage is speed. The
current tests to measure proteins can take days. But the biggest
advantage is how rapidly we can design new sensors from RNA."
According to the NIH, the grants were given to "encourage
investigators to explore bold ideas that have the potential to
catapult fields forward and speed the translation of research into
improved health."
The NIH made 42 awards totaling $30 million. Dr. Jaffrey's award
is $1,690,000, funding the research for five years.
NIH-Funded Study Looks to Reduce Neurodegeneration in
Parkinson's Disease
Compounds May Reduce Oxidative Stress and Inflammation in the
Brain
Synthetic experimental compounds may help to reduce oxidative
damage and inflammation in the brain, a common cause of cell death
in patients suffering from Parkinson's disease and other
neurodegenerative disorders.
The compounds, called synthetic triterpenoids, work by boosting
the activity of anti-inflammatory and antioxidative genes -- by
activating the pleiotropic transcriptional machinery controlled by
the Nrf2/ARE pathway -- within brain tissue. Weill Cornell Medical
College scientists, led by Dr. Bobby Thomas, assistant professor of
neuroscience, hope to determine the most efficient molecule of the
three synthetic triterpenoids (CDDO methylamide, ethylamide or
trifluoroethylamide), which have also been developed in
collaboration with Dr. Michael Sporn at Dartmouth College.
They will test the compounds in mice models of Parkinson's
disease in an effort to determine the neuroprotective efficacy and
the ability to activate the Nrf2/ARE pathway. The researchers hope
their findings will lead to the development of potential
therapeutic drugs to block the death of midbrain dopamine neurons
in Parkinson's disease.
Parkinson's disease currently affects about 1.5 million people
in the United States. The study is funded by stimulus grants from
the American Recovery and Reinvestment Act.
Body's Own Cholesterol Processing May Lead to Innovative
Therapies
High-Tech Imaging Reveals Earliest Stages of Artery Blockage
When waste removal cells called macrophages are overrun by
cholesterol in the blood stream, it can lead to potentially fatal
blockages within arteries. A new Weill Cornell study hopes to
provide a better understanding of how the body's defenses fail to
eliminate cholesterol during the earliest stages of
atherosclerosis, or the hardening of the arteries. Preliminary
findings may represent a new strategy for developing therapies that
prevent the formation of blockages before they occur.
Using high-tech microscopic fluorescent imaging, a team led by
Dr. Frederick Maxfield, chairman of biochemistry at Weill Cornell
Medical College, has observed how the body's cells process
low-density lipoprotein (LDL), commonly referred to as "bad
cholesterol." They have learned that macrophages form a compartment
outside of their cell membrane, called an extracellular lysosome or
a lysosomal synapse. This structure is an organelle containing
digestive enzymes.
Over time, scientists believe that lysosomes cannot keep up with
large amounts of LDL, leading to a build-up within the arteries.
The researchers hope that a complete understanding of the mechanism
may lead to therapies that boost the body's own ability to remove
harmful cholesterol, without initiating harmful reactions in the
macrophages as they attempt to clear the cholesterol.
The study is being funded by stimulus grants from the American
Recovery and Reinvestment Act. According to the American Heart
Association, coronary heart disease is caused by atherosclerosis,
which likely produces angina pectoris (chest pain), heart attack or
both. Coronary heart disease caused 445,687 deaths in 2005 and is
the single leading cause of death in America today.
Making a Better Vaccine
Viral Vector Has Potential for Greater Safety
Weill Cornell scientists are studying a new, safer type of viral
vector -- a harmless virus used to impart immunity to infections --
that may someday be used to engineer vaccines for a variety of
diseases.
Lentiviral vectors are powerful inducers of the body's immune
responses; however, they carry the risk associated with integration
into the host genome by replicating and causing harm. But now a
team of researchers, led by Dr. Mirella Salvatore, assistant
professor of public health at Weill Cornell Medical College, are
studying a new "non-integrating" lentivirus vector that does not
transfer pieces of its DNA into the body's cells.
The virus will still express a protein, without permanently
transferring pieces of DNA to the host. The protein is recognized
by the body, which then mounts an immune response. Dr. Salvatore
believes using an integrase-defective viral vector is a potentially
safer method to create vaccines for the prevention of infectious
diseases such as influenza, HIV, and even cancer. The researchers
will test the vector using the influenza virus on mouse models.
Collaborators on this study include Dr. Andrea Cara, from the
Istituto Superiore di Sanità in Rome, Italy, and Dr. Mary
Klotman, from Mount Sinai School of Medicine, in New York City. The
study is being funded by stimulus grants from the American Recovery
and Reinvestment Act.
New Way to Get a Boost in Energy Disorder
Weill Cornell Researchers Discover Presence of an Enzyme
Responsible for Energy Production Within Cell
Rocco Baldelli, an outfielder for the Boston Red Sox, has a
condition that affects how organelles in his cells, called
mitochondria, produce energy for his body. The condition, called
mitochondrial myopathy, often leaves him fatigued, even after mild
physical exertion. He is not alone -- one in every 5,000 people
suffer from a mitochondrial disorder. Impaired mitochondrial energy
production is also associated with many neurodegenerative
disorders, like Parkinson's disease, Alzheimer's disease,
Huntington's disease, and amyotrophic lateral sclerosis (ALS or
"Lou Gehrig's disease").
Now, Dr. Giovanni Manfredi, professor of neurology and
neuroscience, and his team from Weill Cornell Medical College may
have discovered a new way to someday treat the disorder by boosting
an enzyme within the mitochondria that could directly jumpstart
cellular energy production.
New results published in a recent issue of the prestigious
journal Cell Metabolism show that an enzyme responsible for the
final steps of energy creation within cells, called soluble
adenylyl cyclase (sAC), is produced within the mitochondria
themselves. This finding is significant because it was previously
unknown if the enzyme was produced independently within the
mitochondria, and may, therefore, serve as a specific target for
therapies to boost energy production. According to the researchers,
exclusively targeting the mitochondria is important because
increasing the enzyme throughout the entire cell could cause
malfunctions with other cellular processes.
Currently, Dr. Manfredi's research team is boosting the enzyme
in a rodent model that exhibits mitochondrial disease. Promising
early results show that energy production may be raised and the
animals' symptoms eased.
Co-authors of the study include Drs. Jochen Buck and Lonny
Levin, both professors of pharmacology at Weill Cornell Medical
College.
The study was supported by the National Institutes of Health,
the Muscular Dystrophy Association, American Diabetes Association,
Spanish Ministry of Education Fulbright Fellowship, United
Mitochondrial Disease Foundation, Milstein Foundation, and Medical
Scientist Training Program (MSTP) funding.
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