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NHLBI Funds $22M to Five Institutions for Metabolomic Research into Cardiovascular, Lung Diseases

NEW YORK (GenomeWeb News) – The National Heart, Lung, and Blood Institute has awarded grants totaling $22 million to five institutions to conduct metabolomics research into cardiovascular and lung diseases.

The recipients of the grants are Weill Cornell Medical College; Washington University School of Medicine in St. Louis; Cleveland Clinic; Emory University; and National Jewish Health.

Researchers at Weill Cornell were awarded $6.5 million over five years to investigate metabolic changes in airway epithelial cells in the lungs of chronic obstructive pulmonary disease (COPD) patients. In addition, the grant will go toward research to identify which cigarette smokers are at most risk for developing COPD, and to identify novel biomarkers to help in developing new therapeutic treatments for the disease.

Weill College and its project collaborator Cold Spring Harbor Laboratory will conduct a study aimed at uncovering the underlying genesis of smoking-induced cellular dysfunction within the airway epithelial cells that result in the shortening of cilia cells, mucus accumulation, and the impairment of infection defenses — a process known as ciliopathy.

According to Steven Gross, co-principal investigator on the grant and a professor of pharmacology and director of the Mass Spectrometry Facility at Weill Cornell, the study seeks to "identify what exactly drives ciliopathy in smokers with COPD," he said in a statement from Weill Cornell.

Researchers will use mass spec-based technology to broadly identify, analyze, and profile abnormal changes in cell metabolism and metabolites for COPD in the airway of epithelial cells in the lungs. A global metabolite profiling of lung serum and tissue samples from COPD patients will be performed, and researchers will investigate thousands of small molecules and measure changes in metabolite expression.

They will also combine metabolic profiling with in vitro studies of human subjects and murine airway epithelium, and analyze serum, lung epithelial lining fluid, and airway epithelium samples from human research subjects, as well as an extensive cohort of banked human clinical trial samples. These will be compared in populations of nonsmokers, smokers, COPD smokers, and smokers with and without COPD who underwent smoking cessation.

Washington University received $4.7 million to study heart disease in diabetes with the goal to identify better measures of heart disease in patients with the diabetes.

Its program will have four parts: to establish a clinically useful method for measuring key lipids related to diabetes complications in blood samples; to identify biomarkers of abnormal lipid metabolism in existing blood samples from clinical trial participants, including those in the Framingham Heart Study; to design laboratory experiments to better understand how abnormal lipids may contribute to heart muscle dysfunction; and to conduct a clinical trial for patients with type 2 diabetes to whether blood lipid-lowering drugs improves heart function.

Washington University said it is serving as coordinating center among the five centers which received the NHLBI funding.

Cleveland Clinic received about $4.8 million to discover novel pathways associated with the development of cardiovascular disease.

Stanley Hazen, a co-principal investigator on the project being carried out by the clinic, last year discovered new pathways involved with heart disease, including a dietary nutrient found in animal products that is metabolized by gut flora and is linked to atherosclerosis.

With the NHLBI grant, he and W.H. Wilson Tang, co-principal investigator on the grant, will extend the research to analyze thousands of metabolites in blood, including many formed by gut flora, to discover new pathways linked to heart attacks, strokes, and heart failure.

They also plan to manipulate the bacteria in humans to test whether specific probiotics can be used to treat cardiovascular diseases, Cleveland Clinic said.

NHLBI awarded Emory University a $5 million grant to use mass spec driven research to identify and validate new cardiovascular disease risk biomarkers.

Dean Jones, a professor of medicine and director of the Emory Clinical Biomarkers Laboratory, plans to sort through thousands of substances in blood to find those whose levels match established measures of blood vessel function and coronary artery disease, the university said.

Jones and his collaborators will track disease progression in one group of 900 health individuals enrolled as part of the Emory-George Tech Predictive Health Institute and another group in the Emory Cardiovascular Biobank, consisting of 4,000 patients with suspected cardiovascular disease.

Jones has developed a mouse model of acute atherosclerosis where alterations in blood flow can result in blocked arteries in a few weeks. In the animal studies, the scientists will further investigate and validate biomarkers identified in humans.

The grant to National Jewish Health is for $1 million, a spokesman for NJH said. According to the grant abstract, its work will build on preliminary research conducted at the hospital using metabolomics, genomics, and animal studies that identified dysregulation of sphinolipids "as a crucial step in the pathogenesis of COPD and emphysema."

In further work funded by the NHLBI grant, NJH will focus on identifying candidates who develop chronic airflow limitation and/or emphysema using the NHLBI-sponsored COPDGene cohort, a 10,000 subject, highly phenotyped cohort of smokers with and without COPD.

"Using this integrated metabolomics-genomics-animal model approach, we anticipate that we will identify other dysregulated pathways that can explain why some smokers get COPD and emphysema yet other smokers do not," according to the grant abstract.

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