2009 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
Serpil Erzurum, M.D.
Imaging Inflammation in Asthma
Cleveland Clinic
Dr. Erzurum is an expert in asthma. In her AAF studies, she proposes to open a new field of research in asthma by collaborating with Dr. Frank DiFilippo, an expert in nuclear medicine, physics, and instrumentation. Together, they seek to use new technologies for physicians and scientists to “image” the lung—to see not just x-ray pictures, but also localized areas of inflammation and even chemical reactions in the lung. The technique is called “SPECT” scanning (single photon emission computed tomography), and they will use it to track a molecule in the lung called glutathione, which normally protects the lungs from damage caused by highly reactive oxygen (forms of oxygen similar to ozone). Drs. Erzurum and DiFilippo will take images of the lung that show local changes in glutathione. The use of SPECT scanning will allow new insight into the mechanisms of asthma, and it may provide a noninvasive means for assessing the activity of asthma in patients.
- Read about Dr. Erzurum in the Fall 2011 issue of Cleveland Clinic’s Catalyst
Bruce D. Hammock, Ph.D.
Soluble Epoxide Hydrolase is a Novel Therapeutic Target in Asthma
University of California, Davis
Attacks of asthma are intermittent, but it is now appreciated that they reflect chronic and sustained inflammation of the airways. Sustained inflammation requires the ongoing recruitment of white blood cells, and one important signal for the recruitment of white blood cells involves the breakdown of “fatty acids” within cells. Dr. Hammock has studied the enzymes that cause this breakdown. He will define the role of fatty acid breakdown in asthma, and he will test the therapeutic effect of blocking this breakdown, using either single drugs or a combination of therapies.
To learn more about Dr. Hammock’s research visit The Hammock Lab by clicking here
William Harnett, Ph.D.
Application of a Parasitic Helminth Product to the Understanding and Treatment of Asthma
University of Strathclyde
Over the last 20 years, asthma has been rapidly rising in developed countries, but the increase has been slower in developing countries. One hypothesis is that asthma may be inhibited by parasitic infection, particularly infection with intestinal worms, which are more prevalent in developing countries. Dr. Harnett has discovered that parasitic worms make a molecule, called ES-62, which can block immune events known to be important in asthma. He proposes to study the mechanisms of this effect and to test the effects of ES-62 on asthma in mice. The ultimate goal is to use the ES-62 molecule as a model for developing new drug therapies for asthma.
Raphael Kopan, Ph.D.
The Role of Skin-derived TSLP in the Atopic March Connecting Atopic Dermatitis with Asthma
Washington University
Asthma is notably more common in children who have skin allergies. Recent studies have suggested that breakdown of the skin may release a protein, called TSLP (thymic stromal lymphopoietin), which promotes asthma. Dr. Kopan and his colleagues will define the causes of TSLP release by the skin and they will seek to block this. If successful, this will open new pathways for treating atopic skin disease and preventing the associated asthma.
Dean Li, M.D., Ph.D.
Blunting the Effects of Cytokines on the Asthmatic Lung
University of Utah
Current therapies for asthma are directed against either the tightening of airway muscles, which cuts off the air supply, or the chronic inflammation that leads to airway constriction. Dr. Li proposes yet a third approach, to protect lung cells from damage by inflammation. He has found that proteins normally present in the brain and on the lining of blood vessels (“Robo” proteins) are also on the cells that line the airways and other cells in the lungs. These proteins normally protect cells from the damaging effects of infection with virus or bacteria. Dr. Li will test the importance of Robo proteins in the lungs of mice in protection against asthma. If Robo proteins are important in asthma, potential new therapies will be tested.
Xiaoxia Li, Ph.D.
Molecular Mechanism for IL-25-mediated Th2 Responses
Cleveland Clinic
The immune response that causes asthma is promoted when a molecule called IL-25 (interleukin-25) is released into the lungs. Immune cells carry receptors for IL-25, and they become activated when encountering these molecules. Dr. Li has found an important new mechanism for controlling the response to IL-25. She has identified a molecule, called Act1, which is important in this response. She will now define the importance of Act1 in lung inflammation and asthma, testing whether this may provide a new target for the therapy of asthma.
Rui Wang, M.D., Ph.D.
Altered Metabolism of H2S in the Lung: A Novel Biomarker and Therapeutic Avenue for Asthma
Lakehead University
Hydrogen sulfide (H2S) is a chemical that is partly responsible for the familiar smell of rotten eggs, and in high concentrations it can be toxic to humans. Normally, though, the body produces a low level of H2S, which is essential for normal biological activity. Dr. Wang has pioneered studies of the role of H2S in the body, including its effect on muscle relaxation and blood pressure. H2S levels are generally lower in asthma, but it is not clear whether this is a cause or an effect of asthma. Dr. Wang will define the relationship between H2S and asthma and will test whether asthma can be improved by supplying H2S in order to relax the muscles that close the airways in asthma.
Charles Zuker, Ph.D.
Neuronal Aspects of Asthma
Columbia University
Dr. Zucker is an expert on the nerves that determine taste and smell. He will use his expertise on the nervous system to study asthma. His first step is to identify the nerves that control airway tightening in asthma, and he then will define the genes in these nerves that are actively making proteins. These proteins will be evaluated as potential therapeutic targets for asthma, opening the airways by blocking their activity in nerves.
Early Excellence Awards
Matthew Krummel, Ph.D.
Directing Antigens to Specific APC and T Cell Subsets in the Lung
University of California, San Francisco
Dr. Krummel is developing new ways to examine the functions of immune cells by observing them under powerful microscopes in living lung tissue. In his AAF studies, he seeks to answer the question of why asthmatics have a strong allergic response to some inhaled allergens, such as specific pollens, but have no response to others. He will study in particular the white blood cells that first take up the inhaled allergens and which then present these to the immune system. He will determine if different types of white blood cells respond to different types of allergic stimuli and elicit different immune responses. This type of study has not been possible until recently, when advances in technology allowed tracking the immune response in vivo. Dr. Krummel’s studies hold the promise of identifying more selective targets for treating asthma.
To learn more about Dr. Krummel’s research visit The Krummel Lab by clicking here
Michael McAlpine, Ph.D.
Prevention and Diagnosis of Asthma via Ultra-sensitive and Selective Molecular Nanosensors
Princeton University
Dr. McAlpine proposes to build a portable nanotechnology device to study asthma. He will devise tiny sensors to simultaneously monitor particles in the air that may cause asthma, as well as the chemicals present in exhaled air from asthmatic patients. He will look for chemical patterns that distinguish the composition of exhaled breath during an asthmatic response from normal breathing. There is nothing like this currently available. Success in this endeavor will open a new field of research into the causes of asthma by allowing scientists to better characterize particles that trigger asthma attacks as well as to detect the resulting asthmatic response. Further, it may help to distinguish different types of asthma, allowing more specific therapies.
To learn more about Dr. McAlpine’s research visit the McAlpine Research Group by clicking here
Daniel Minor, Jr., Ph.D.
Structural Studies of Calcium-activated Chloride Channel Modulation and Function
University of California, San Francisco
Normal airways produce a thin layer of mucus, which protects the airways cells and serves as a vehicle to expel foreign particles from the lungs. The most common cause of death from asthma is overproduction of airway mucus, leading to asphyxiation. The production of mucus by airway cells is regulated by a protein called CaCC, which resides on the surface of the airway cells and allows the passage of calcium into the cell. The gene for CaCC was discovered in 2008. This discovery allows the work proposed by Dr. Minor, to define the molecular structure of CaCC. This is essential for designing a drug that can alter CaCC, preventing the fatal overproduction of airway mucus in asthma.
Adrian Salic, Ph.D.
Mechanism and Function of Platelet-activating Factor,a Critical Molecule in Asthma
Harvard University
Allergy and inflammation are promoted by a molecule called platelet-activating factor (PAF). Dr. Salic has discovered a method by which molecules similar to PAF can be observed under a microscope within living cells. He is refining his technique in order to specifically detect PAF molecules, which will allow him to track the movement of PAF in living cells under various conditions. By observing the activity of PAF in live cells, he will be able to identify the genes that control the synthesis of PAF, its transport within cells, and its release from the cell to promote inflammation. Each gene he identifies that controls the generation of PAF is a potential therapeutic target for asthma.
To learn more about Dr. Salic’s research visit The Salic Lab by clicking here
