2010 Research Grant Awardees
The American Asthma Foundation awards grants to investigators who are pursuing new, breakthrough pathways for treating, preventing, and curing asthma.
Senior Investigator Awards
Daniel J. Dumont, Ph.D.
Manipulating the Angiopoietin Signaling Axis to Treat Asthma
Sunnybrook Research Institute at the University of Toronto, Canada
Angiopoietins are natural proteins that promote the formation and growth of new blood vessels. Injection or inhalation of one of the angiopoietins, angiopoietin1, suppresses asthma in mice. Dr. Dumont has developed a synthetic peptide (small protein) that mimics the effects of angiopoietin1, but is more stable and more readily delivered as a therapy. He will now study the effects of this peptide on asthma in mice, define how it works, and refine methods for delivering the peptide as a drug. If the peptide is effective, completion of these studies could lead to further testing and clinical trials.
Evan E. Eichler, Ph.D.
Comprehensive Analysis of the Effects of Copy Number Variation on Asthma
University of Washington, Seattle, WA
Dr. Eichler proposes to bring an important advance in genetics to the study of asthma. He will go beyond comparison of gene sequences between asthmatics and nonasthmatics by testing the hypothesis that asthmatics have more (or fewer) copies of important genes than do nonasthmatics. This approach has been shown to be important in the genetics of several other inflammatory diseases.
Stuart B. Hooper, Ph.D.
Imaging Lung Motion for Studying the Dynamics of Asthma and Its Treatments
Monash University, Victoria, Australia
In order to better understand asthma, scientists need to be able to examine what is happening in the lung during an asthmatic attack. It is difficult to capture detailed images of the lung, particularly during a breath because breathing-related movement of the lung causes image blurring. As a result, breathing must normally be halted briefly to acquire an image of the lung while it is stationary. Prof. Hooper and his collaborators have developed methods for looking at the lung with greatly enhanced resolution, allowing many images to be captured during a single breath. This approach not only overcomes the problem of lung motion, but also uses lung motion as one important measure of how different regions of the lung function during breathing. He will apply these techniques to the study of asthma in mice and, in particular, to assess how the lung’s movement is altered by asthma and in response to known therapies.
Richard M. Maizels, Ph.D.
Suppression of Airway Allergy by Products of Helminth Parasites
University of Edinburgh, Scotland
Dr. Maizels has shown that allergic responses in mice can be suppressed by a parasitic worm, and he has begun to dissect the mechanisms of this suppression. As part of this work, he has isolated a group of proteins that are produced by the worm and that mimic the effect of the whole worm on immune suppression. He will now take two paths to defining new therapies for asthma. First, he will define the mechanisms by which asthma is suppressed by the worm proteins as a group. Second he will identify the individual worm proteins that mediate the suppression of asthma, seeking new therapeutic agents for asthma treatment.
Andrew N. McKenzie, Ph.D.
The Role of Nuocytes in the Regulation of Asthma
MRC Laboratory of Molecular Biology, Cambridge, England
Dr. McKenzie examines the mechanisms by which the immune system attacks parasites. Through his work he has defined a new cell in the immune system (the “nuocyte”) that may be important in asthma. Specifically, the nuocyte is an immune cell that responds to worm infection by producing a protein, called IL 13, which is known to promote asthma. Dr. McKenzie will test the hypothesis that nuocytes may be important in the asthmatic immune response. He will also define how nuocytes develop in asthma, so that they may be eliminated as a means of preventing or treating asthma.
Kevin J. Tracey, M.D.
Targeting Nicotinic Acetylcholine a7 Receptors in Allergic Lung Inflammation
Feinstein Institute for Medical Research, Manhasset, NY
Dr. Tracey has previously demonstrated that immunity and inflammation are regulated in part by the nervous system. He will apply lessons from this work to the study of asthma. He has identified a protein (receptor) on the surface of blood cells that suppresses inflammation when it binds to chemicals released by nerves. Additionally, he has developed an artificial chemical compound that mimics the effect of the neurologic signals, thereby suppressing inflammation independently of the nervous system. Dr. Tracey will directly test the effect of this compound on asthma. Additionally, he will pursue other avenues to establish the importance of this connection between nerves and inflammation as a possible path for future new ways of treating asthma.
Dario A Vignali, Ph.D.
Interleukin-35, iTr35 and Allergic Asthma
St. Jude Children’s Research Hospital, Memphis, TN
Cytokines are proteins that are released by cells and serve as “messengers” that cause other cells to turn on, turn off or otherwise change their behavior. Cytokines allow cells to talk to each other at a distance during an infection or an allergic response. Dr. Vignali has discovered a new cytokine, called IL 35, which dampens the immune response that characterizes asthma. Dr. Vignali will test the importance of IL 35 in the normal regulation of asthma and the use of IL 35 in treating asthma.
H. Eric Xu, Ph.D.
Molecular Mechanism of Dissociated Glucocorticoids
Van Andel Research Institute, Grand Rapids, MI
Steroids are a mainstay in the treatment of asthma. However, steroids are often accompanied by side effects that can include bone loss, bone fracture, diabetes, and cataracts. Even though inhalation of steroids lessens their side effects, the side effects nonetheless exist. Dr. Xu is trying to make it possible to use steroids for the treatment of asthma and other diseases without their side effects. At the molecular level, there is considerable evidence that the beneficial effects of steroids can be separated from their detrimental effects, but this has not yet been successfully translated into therapies that separate these activities. Dr. Xu proposes to define the structural requirements for the beneficial vs. harmful effects of steroids and for creating new steroid-like molecules that will promote benefit while minimizing harm. Success in this venture would be of great help to the treatment of asthma and many other inflammatory diseases.
Early Excellence Awards
Brian A. Cobb, Ph.D.
Commensal Antigen-induced T Regulatory Cells in Airway Tolerance
Case Western Reserve University, Cleveland, OH
Dr. Cobb’s proposal builds on the “hygiene hypothesis,” in which exposure to bacteria early in life protects against asthma. His prior research provides evidence that a specific bacterium, Bacteroides fragilis, which is frequent among gut bacteria, may lead to immune suppression. Dr. Cobb will test the hypothesis that a carbohydrate produced by B. fragilis activates “T regulatory cells,” which are cells that suppress immunity. These studies may open the path to a specific means of suppressing asthma by a bacterium that is otherwise thought to live in the gut without adversely affecting humans.
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Andre Levchenko, Ph.D.
Integrative Biology-based Investigation of Interplay between Inflammatory Signaling
Johns Hopkins University, Baltimore, MD
Dr. Levchenko proposes to use new technologies to study how asthma alters the function of muscle cells that close the airways. Contraction of these muscles is regulated both by proteins that are produced during inflammation (cytokines) and by tissue proteins and non-muscle cells that are normally in direct contact with the muscles. To examine all of these factors together, Dr. Levchenko will use nanotechnology, growing airway muscle cells on tiny surfaces that mimic the normal lung, thus creating a system in which he can measure both the contraction of the muscle cells and their ability to change shape. If successful, these studies may reveal new pathways in the regulation of asthma attacks and the techniques will also greatly facilitate other investigations of human asthma.
Carla M.P. Ribeiro, Ph.D.
IRE1-beta-Dependent Airway Mucin Production and ATP Release: A New Pathway in Asthma
University of North Carolina at Chapel Hill, NC
The primary cause of death in asthma is the excessive production of mucus (“mucin”), which fills the airways, in effect causing drowning. Dr. Ribeiro proposes to define a pathway by which asthma causes increased production of mucin in the airways. She has previously identified an enzyme, called IRE1-beta, which is selectively expressed in the mucin-producing cells of the airways and intestine. She has further shown that expression of this enzyme correlates with the production of mucin. Dr. Ribeiro will examine the molecular pathways by which IRE1-beta may stimulate the production of mucin in asthma, thus establishing new potential targets for therapy.
Thaddeus S. Stappenbeck, M.D., Ph.D.
Role of Microbial Driven Autophagy within Respiratory Airways in the Pathology of Asthma
Washington University, St. Louis, MO
Although it was once thought that the airways are sterile, recent studies suggest that this is not so; bacteria are found in the airways of normal lungs and are increased in the presence of inflammation. Dr. Stappenbeck, who has previously studied the role of beneficial bacteria on the cells that line the intestine, proposes that certain bacteria help to maintain the normal function of the cells that line the airways, regulating the production of mucin. He will test the role of specific bacteria on the production of mucus by airway cells. He will also use bacteria as probes to alter the activity of airway cells, searching for new molecular targets for asthma therapy.
Extension Award
Sven-Eric Jordt, Ph.D..
Sensory Chemoreceptors in Asthma and Airway Hyperresponsiveness
Yale University, New Haven, CT
Through his Early Excellence Award, Dr. Jordt made the remarkable discovery that asthma in mice is dependent on a subset of “sensory” nerves that can detect certain chemicals. More specifically, he showed that asthma does not develop if mice cells lack a specific surface protein on nerves, called TRPA1. TRPA1 is involved in sensing chemicals, including ozone and chlorine, and it responds by allowing ions such as calcium to enter nerve cells. TRPA1 plays a role in cough and sneezing, but its role in asthma had not previously been demonstrated. Dr. Jordt additionally showed that by blocking the function of TRPA1 with a chemical inhibitor he could inhibit asthma in mice. He will use his Extension Award to further test this inhibitor of TRPA1 in mice, as well as to test potentially more powerful inhibitors.
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Dr. Eichler proposes to bring an important advance in genetics to the study of asthma. He will go beyond comparison of gene sequences between asthmatics and nonasthmatics by testing the hypothesis that asthmatics have more (or fewer) copies of important genes than do nonasthmatics. This approach has been shown to be important in the genetics of several other inflammatory diseases. |
