YALE UNIVERSITY SCHOOL OF MEDICINE
PUBLIC INFORMATION
100 CHURCH ST. SOUTH, SUITE 212
P.O. BOX 7612 NEW HAVEN, CT 06519-0612

CONTACT: Helaine Patterson
(203) 785-5824

EMBARGOED FOR SUNDAY JANUARY 26, 1997

MAJOR ASTHMA RESEARCH PROGRAM STARTS AT YALE National Institutes of Health Names Yale One of Seven Centers Awards Medical School $8.6 Million Grant

NEW HAVEN, Conn., Jan. 26, 1997--The National Heart, Lung and Blood Institute (NHLBI) has selected Yale University School of Medicine as one of seven locations in the United States to establish a Specialized Center of Research to understand the causes of asthma. To conduct this research the NHLBI, a component of the National Institutes of Health, has awarded $8.6 million to Yale over the next five years.

"Asthma is so common now that it has become a major health-care issue," points out Jack A. Elias, M.D., director of this new Yale medical research center. "Approximately 15 million children and adults in the United States suffer from asthma, a chronic condition in which their airways become chronically inflamed. The frequency of asthma appears to be particularly prominent in inner-city areas. In the last 15 years, asthma has become an increasingly severe health problem, even reaching epidemic proportions," he adds. Since the early 1980s, national statistics show that the prevalence (frequency) and death rates due to asthma have increased by approximately 40 percent.

Yale physicians in internal medicine, pulmonary medicine, critical care medicine and occupational and environmental medicine will join scientists from the section of immunobiology, the departments of pathology, laboratory medicine and comparative medicine, and the John B. Pierce Laboratory to conduct studies designed to understand the inflammation in airways of patients with asthma. This multidisciplinary team will be headed by Dr. Elias, professor of medicine and chief of pulmonary and critical care medicine at the Yale University School of Medicine.

The research's major focus will deal with the cellular and molecular biology of asthma. "Our research will center on three main themes," Dr. Elias notes. "The first are cytokines, small proteins that cells make to communicate with one another. Secondly, we will explore certain kinds of cells, called T lymphocytes, which are small cells that are considered to be the 'orchestra leaders' of the inflammatory response in the airways of people with asthma.

"Thirdly, intense studies will be undertaken of a particular type of occupational asthma seen in patients who are exposed to chemicals frequently found in plastics and spray paint. A subset of people are sensitive to and experience asthma attacks when they come in contact with these chemicals. A particularly high frequency of this type of asthma has been noted in sick patients who are autobody workers in Connecticut.

"Since our research center's goal is to gain additional information about the cellular and molecular causes of asthma," Dr. Elias says, "we hope that these molecular studies conducted at Yale will lead to an improved understanding of the basic science of asthma and to the development of improved treatments for it. For example, we may be able to block or get rid of a problematic cytokine or a disease-causing lymphocyte population." The ultimate goal of all of the studies will be to generate the type of knowledge upon which new treatments for asthma can be based.

The Yale Asthma Research Program encompasses six major projects studying the cellular and molecular mechanisms of asthma. The projects and their leaders are described below.

∑ Interleukin-11 in Viral Asthma. Jack A. Elias, M.D., professor of medicine and chief of pulmonary and critical care medicine. These studies will investigate the role that the cytokine interlukin-11 plays in viral infections and the mechanism by which viral infections lead to asthma attacks.

∑ Regulation of Th2 Effector Function in the Airways. Kim Bottomly, Ph.D., professor of immunobiology and biology, and associate investigator at the Howard Hughes Medical Institute. These studies will investigate the processes that regulate the generation and function of a specific lymphocyte population, known as Th2 lymphocytes, and the role that they play in mediating asthma.

∑ Molecular Analysis of IL-5 Gene Transcription. Anuradha Ray, Ph.D., assistant professor of medicine (pulmonary). Dr. Ray's study is focusing on a cytokine, called interlukin-5 (IL-5), which plays an important role in asthma. Interleukin-5 recruits a particular type of white blood cells, called eosinophils, to the lungs of people with asthma. These cells are believed to be responsible for many of the manifestations of asthma. Her studies are designed to determine what processes regulate the production of interleukin-5.

∑ Transgenic Modeling of Airway Inflammation in Asthma. Jack A. Elias, M.D. This study is centering on the use of transgenic technology in which human genes can be implanted into laboratory mice. These studies will allow Dr. Elias and his colleagues to determine which genes are likely to generate asthma-like features such as inflammation, wheezing and mucous production that people with asthma experience.

∑ Cytokines and Adhesion Molecules in Hapten-Induced Airways Hyperresponsiveness. Gregory P. Geba, M.D., assistant professor of medicine (pulmonary). This study is concentrating on the development of a new model of asthma in laboratory mice, based on generating a delayed form of airway inflammation. Dr. Geba and his colleagues will be determining what starts the inflammatory response and what turns it off. In addition, they will explore the mechanisms by which inflammatory cells enter the airways of these animals.

∑ T Cells in the Pathogenesis of Human Isocyanate Asthma. Carrie A. Redlich, M.D., associate professor of medicine (occupational and environmental medicine). This research is designed to study the mechanisms of inflammation in the airways of adults exposed to chemicals used in the autobody industry in Connecticut.

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