Deep-sea microbe illuminates workings of human brain
|The bowl-shaped structure of the glutamate transporter may be important in the development of new drugs for schizophrenia and depression.
Reaching far down the evolutionary ladder, Eric Gouaux Ph.D., and his team of structural biologists have uncovered from a microbe the shape of a protein that is also used by human neurons to control cell-to-cell communication.
It is unclear what the protein does in microbes, but in human brains the protein acts like a molecular vacuum cleaner to clean up the synapse, the space between neurons that enables neurons to communicate. During neuron-to-neuron communication, one cell sends small neurotransmitters across the synapse to another cell. When the neurotransmitters are received, the "vacuum cleaner" proteins called neurotransmitter transporters prepare the synapse for the next message by quickly clearing any leftover molecules from the space.
Numerous brain disorders, including schizophrenia, epilepsy, and depression, stem from too many or too few neurotransmitters in the synapse, so the detailed picture of the synapse's neurotransmitter transporters may aid the development of new drugs. Some available drugs already hone in on these proteins, including antidepressants like Prozac, which block the serotonin transporter to increase the amount of serotonin in the synapse.
Dr. Gouaux, professor of biochemistry and molecular biophysics, together with postdoctoral fellows Olga Boudker and Dinesh Yernool and senior technician Yan Jin, solved the structure of the glutamate transporter, one of several different types used by the brain. This is the first time a neurotransmitter transporter structure has been elucidated. The research appeared in the Oct. 14, 2004, issue of Nature.
Caribbean Hispanics Prone to Stroke
Hispanics experience stroke twice as often as Caucasians and new research from CUMC's Northern Manhattan Family Study suggests genetic predisposition may be related to stroke risk in Hispanics.
The findings show that about 40 percent of variability in carotid intima-media thickness (IMT) the combined thickness of the inner and intermediate layers of the carotid artery is accounted for by genes in Caribbean Hispanics. The results were published in the October 2004 issue of Stroke.
Carotid IMT is a measure of subclinical vascular disease and a strong predictor of stroke, as well as myocardial infarction and vascular death. The risk factor applies to all ethnicities but may be particularly important for Hispanics because they tend to have a greater prevalence of hypertension and diabetes, important determinants of IMT.
Finding those genes, and genes for other risk factors, could lead to drugs to prevent stroke or screening tests to predict risk, say the paper's lead authors Suh-Hang Hank Juo, M.D, Ph.D., assistant professor of epidemiology in the Columbia Genome Center, and Ralph Sacco, M.D., professor of neurology and epidemiology in the Sergievsky Center.
The researchers also found that obesity and carotid IMT share common genes. The researchers say that if a therapy is found to reduce IMT, that therapy may also reduce obesity.
Columbia Cardiologists are Strong Presence at AHA Meeting
Promising news about drug-coated stents, adult stem cells, and a new valve repair procedure was presented by CUMC researchers at this year's annual American Heart Association (AHA) meeting in New Orleans in November. With about 30,000 attendees and more than 3,800 oral and poster presentations, the AHA annual meeting is the premier cardiovascular research meeting in the world.
Following are a few highlights of Columbia's research:
Gregg Stone, M.D., professor of medicine, reported that in a trial of 1,314 patients with paclitaxel-coated TAXUS stents the largest drug-coated stent trial in the United States the stent continues to keep blockages in the heart at bay a full two years after implantation. The results dispel concerns that the new stents may only be effective for a short time. Dr. Stone is also director of cardiovascular research and education at CUMC's Center for Interventional Vascular Therapy.
Since their approval by the FDA in 2002, drug-coated stents have revolutionized the treatment of coronary artery disease. The stents prevent the regrowth of arterial blockages that frequently occur with bare metal stents. An estimated 1 million people in the United States will receive the drug-coated stents this year.
About 5 million people in the United States have heart failure. Apart from heart transplants, however, current therapies can only slow the progression of the disease. Now, Hina Chaudhry, M.D., Irving Assistant Professor of Medicine, has found that genes responsible for building heart muscle normally turned off after birth appear to be re-activated in heart failure patients in the presence of certain types of stem cells.
The findings imply that future cell-based therapies may be able to harness these genes to grow new cells in damaged regions of the heart. Dr. Chaudhry looked at 24 patients with heart failure and found that a few had stem cells in their hearts and that the presence of the stem cells correlated with a limited degree of heart muscle regeneration.
A new nonsurgical method to repair mitral regurgitation in the heart appears to be feasible and safe, according to results from a phase I clinical trial at CUMC and six other institutions. About 40,000 Americans undergo surgery every year to fix a leak in the mitral valve which, if left unrepaired, can eventually lead to heart failure.
The new minimally invasive procedure mimics a surgical repair by using a catheter inserted into the femoral vein to attach a clip to the heart's mitral valve. The clip successfully repaired the valve in 23 of 27 patients enrolled in the trial. The other four had elective open heart surgery. No significant adverse events have been noted. At CUMC, the trial is being led by Hal Wasserman, M.D., associate clinical professor of medicine.
CUMC researchers Shi Fang Yan, M.D., assistant professor of surgical science, and Martin Andrassy, M.D. (former postdoctoral research scientist), won a "best poster" award for work that identifies a key molecule in the heart that causes tissue damage after a heart attack. The molecule, protein kinase C beta (PKCbeta), is activated soon after the blood supply returns and initiates a cascade of events that damage the tissue long after the heart attack is over. Blockage of PKCbeta could reduce injury and enhance recovery after myocardial infarction.