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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