Research Program > Research Breakthroughs | 2009 Research Grant Awardees

Research Breakthroughs

The American Asthma Foundation has funded a broad spectrum of new asthma initiatives, all directed at improving treatment, preventing, and finding a cure for this disease. Summarized below are some of the studies that have opened new pathways to understanding asthma. Several of these have led to support from industry to develop new therapies, and three have led to clinical trials of new treatments for asthma.

  • Michael Blackburn, Ph.D.Treating Asthma with a Drug Used to Treat Immune Deficiency Biochemistry and Molecular Biology, University of Texas Health Sciences Center at Houston
  • Richard Bond, Ph.D.Turning the Treatment of Asthma on its Head Pharmaceutical Sciences, University of Houston
  • David Christianson, Ph.D.Blocking an Enzyme with Multiple Effects on Asthma Chemistry and Chemical Biology, University of Pennsylvania
  • David Clapham, M.D., Ph.D.Preventing the Airway Muscles from Squeezing the Airways During Asthma Attacks Cardiology, Children’s Hospital, Boston
  • Marco Conti, M.D.Bringing New Precision (and Fewer Side Effects) to the Treatment of Asthma Reproductive Biology, University of California, San Francisco
  • Michael Croft, Ph.D.Stopping Inflammation in Asthma by Blocking Immune Cell Communication Immunochemistry, La Jolla Institute for Allergy and Immunology
  • Joe DeRisi, Ph.D.A Simple Method for Detecting Known Viruses Affecting Asthma Microbiology and Immunology, University of California San Francisco
  • K. Christopher Garcia, Ph.D.New Information that Permits Designing Drugs for Asthma Molecular and Cellular Physiology, Stanford University
  • Mike Holers, M.D.Taming Natural Defenses that Cause Harm in Asthma Rheumatology, University of Colorado Health Sciences Center
  • Robert Lefkowitz, M.D.“Arresting” Inflammation in Asthma Biochemistry and Medicine, Duke University
  • Eric Olson, Ph.D.Controlling Genes that Control Asthma Molecular Biology, University of Texas Southwestern Medical Center at Dallas
  • Daphne Preuss, Ph.D.The Role of Pollens: More Than We Thought Molecular Genetics and Cell Biology, University of Chicago/Howard Hughes Medical Institute
  • Danuta Radzioch, Ph.D.Treatment of Asthma with a Drug Previously Used Only on the Skin Infection and Immunity Axis, McGill University
  • Jonathan Stamler, M.D.Restoring the Ability to Keep Airways Open in Asthma Biochemistry, Duke University
  • Kevan Shokat, Ph.D.Synergy Between Investigators Opens New Approach to Asthma Chemical Biology, University of California, San Francisco
  • Jenny P-Y Ting, Ph.D.Newly Discovered Pathways to Inflammation Microbiology and Immunology, University of North Carolina at Chapel Hill
  • Ralph Weissleder, Ph.D.Visualizing the Lungs During an Attack of Asthma Radiology, Harvard Medical School

  • Michael Blackburn, Ph.D.

    Treating Asthma with a Drug Used to Treat Immune Deficiency Biochemistry and Molecular Biology, University of Texas Health Sciences Center at Houston

    A genetic cause of immune deficiency in children is the lack of an enzyme called adenosine deaminase (ADA), and pat ients lacking ADA can be treated by replacing the enzyme. Dr. Blackburn has found that treatment with ADA unexpectedly reduces lung inflammation in animal models for asthma, and ADA thus prevents long-term damage to the lung. Dr. Blackburn has entered into an agreement with ENZON Pharmaceuticals, the company that makes ADA, to examine the use of ADA in the treatment of asthma and other lung diseases.
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  • Richard Bond, Ph.D.

    Turning the Treatment of Asthma on its Head

    Many patients with asthma inhale drugs called ‘β-agonists’, such as albuterol, which open the airways. Drugs called ‘β-blockers’ oppose the action of β-agonists. Although β-blockers have long been used for diseases such as hypertension, they are usually forbidden in patients with asthma because they may make asthma worse. From his studies of animals,however, Dr. Bond has surprising evidence that this may not be true in the long run; asthma may instead improve with low daily doses of β-blockers. Dr. Bond and his colleagues are now testing low-dose β-blockers in humans with asthma. If this works as it does in animals, it will turn the treatment of asthma on its head—small doses of what was once thought a ‘poison’ in asthma will instead be used to treat it.
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  • David Christianson, Ph.D.

    Blocking an Enzyme with Multiple Effects on Asthma Chemistry and Chemical Biology, University of Pennsylvania

    The lungs of both mice and humans with asthma have an increase in an enzyme called arginase, which is present only in low levels in healthy lungs. The activity of this enzyme has multiple effects that make asthma worse, namely closing airways, increasing secretions in the lungs, and causing permanent scarring in airways. For these reasons, it is desirable to find drugs that block the activity of arginase. Dr. Christianson is seeking to do just this by determining the molecular structure of arginase. This will allow him to develop drugs that bind to arginase and block its activity. The ultimate goal is to develop drugs that can be inhaled to prevent or reverse an attack of asthma.
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  • David Clapham, M.D., Ph.D.

    Preventing the Airway Muscles from Squeezing the Airways During Asthma Attacks Cardiology, Children’s Hospital, Boston

    The sudden difficulty in breathing that occurs in asthma is due to muscles around the airways, which tighten and squeeze the airways. This muscle tightening requires the entry of calcium into muscle from the surrounding tissues. Dr. Clapham has developed a treatment for asthma that blocks the entry of calcium into airway muscle cells. He has cofounded a company that will continue his work to test the use of these drugs in asthma.
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  • Marco Conti, M.D.

    Bringing New Precision (and Fewer Side Effects) to the Treatment of Asthma Reproductive Biology, University of California, San Francisco

    For many years asthma was treated with theophylline, a drug that is related to caffeine. But the use of theophylline was limited by its side effects, some of which can be dangerous. Based in part on Dr. Conti’s work, several drug companies have developed drugs that are more selective in their action and should thus have fewer side effects. One of these is in advanced (Phase-3) clinical trials. Dr. Conti’s AAF-supported work has shown the feasibility of making drugs that are even more selective in their action, but just as effective, further reducing side effects. Two pharmaceutical companies have developed patents based on this work.
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  • Michael Croft, Ph.D.

    Stopping Inflammation in Asthma by Blocking Immune Cell Communication Immunochemistry, La Jolla Institute for Allergy and Immunology

    In asthma, the immune system becomes overactive in the lungs, causing inflammation and damage to the lungs. Dr. Croft found a new way to block the overactive immunity in asthma by blocking proteins (called OX40 and OX40L) on the surface of immune cells. These two proteins interact with each other, allowing the immune cells to “talk” to each other, sending signals to activate immunity. Dr. Croft’s work has led Genentech, in collaboration with Roche Pharmaceuticals, to pursue a new therapy that will prevent the interaction between OX40 and OX40L. This approach is now in clinical trials.
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  • Joe DeRisi, Ph.D.

    A Simple Method for Detecting Known Viruses Affecting Asthma Microbiology and Immunology, University of California San Francisco

    Asthma attacks are often brought on by viral infection, but we understand too little about which viruses are especially prone to cause an attack. To solve this problem, Dr. DeRisi and his colleagues used cutting-edge technology to develop a tiny chip that can detect all known viruses that infect humans. This is being used to track viral infection in asthma. It has also been important in other illnesses and was used to first identify the SARS virus.
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  • K. Christopher Garcia, Ph.D.

    New Information that Permits Designing Drugs for Asthma Molecular and Cellular Physiology, Stanford University

    Attacks of asthma are launched and sustained by molecules called ‘cytokines’, which circulate through the body to activate the immune system. This attack is useful for defending against infections, but in asthma the response goes astray, causing unnecessary inflammation of the lungs and narrowing of the airways. To block this response in the lung, it would be useful to have drugs that prevent the cytokines from binding to immune cells in the lung. To this end, Dr. Garcia, has defined the exact shapes of molecules on the cell surface that can bind to cytokines that cause asthma. This allows chemists to design drugs that will block the binding by cytokines, arresting the immune responses that cause asthma. In fact, a 2008 AAF grant to Gregory Verdine, at Harvard proposes just that—to develop new drugs for asthma based on Garcia’s work.
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  • Mike Holers, M.D.

    Taming Natural Defenses that Cause Harm in Asthma Rheumatology, University of Colorado Health Sciences Center

    Dr. Holers has shown that natural defenses, normally used against infections, may cause harm in asthma. These defenses are collectively called the complement system. Dr. Holers has shown in animals that blocking one part of this defense system prevents inflammation in asthma. The biotech company Taligen Therapeutics is developing this approach for future testing in humans.
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  • Robert Lefkowitz, M.D.

    “Arresting” Inflammation in Asthma Biochemistry and Medicine, Duke University

    The cells that cause inflammation in asthma express proteins called β-arrestins. Dr. Lefkowitz has previously shown that heart and vascular diseases involve β-arrestins. As part of his award, he and his colleague, Julia Walker, demonstrated in animals that β-arrestins are required for the development of asthma. This led to a patent regarding inhibition of β-arrestins in asthma, and Dr. Walker is pursing studies of how arrestins might be blocked to prevent asthma.
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  • Eric Olson, Ph.D.

    Controlling Genes that Control Asthma Molecular Biology, University of Texas Southwestern Medical Center at Dallas

    The closing of airways in asthma involves inappropriate contraction of airway muscles, which also grow in size and strength. These changes are genetically regulated, and Dr. Olson has identified molecular pathways in the cell that control the genetic changes. These studies have the potential to lead to the development new therapies, including drugs that could mimic the actions of corticosteroids with fewer side effects.
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  • Daphne Preuss, Ph.D.

    The Role of Pollens: More Than We Thought Molecular Genetics and Cell Biology, University of Chicago/Howard Hughes Medical Institute

    Pollens are a major trigger to allergy and asthma. Testing for allergy to pollens involves skin tests with extracts from the plants that produce pollens. Dr. Preuss and her colleagues have shown that the preparation of these extracts often removes the parts of allergens that are most important in causing allergy and asthma. She has developed new tests that can rapidly, accurately, and inexpensively detect allergies using only a small amount of blood. This holds great potential for defining allergies in asthma and for customizing therapy to each individual.
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  • Danuta Radzioch, Ph.D.

    Treatment of Asthma with a Drug Previously Used Only on the Skin Infection and Immunity Axis, McGill University

    Dr. Radzioch’s studies led her to test a compound called S28463 (a.k.a. resiquimod), developed by 3M Pharmaceuticals. This drug is clinically used as a topical treatment for skin conditions, including skin cancer. When Dr. Radzioch gave S28463 to animals, it almost completely blocked the development of asthma. In partnership with 3M and Grace Pharmaceuticals, she is now conducting studies monitoring the safety of this compound so clinical trials can start in asthma.
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  • Jonathan Stamler, M.D.

    Restoring the Ability to Keep Airways Open in Asthma Biochemistry, Duke University

    Cells in normal airways make a small molecule called GSNO, which keeps the airways open. Dr. Stamler and his colleagues found that GSNO falls to low levels in asthma, and that asthma in animals is improved when GSNO is restored. Based on this work, N30 Pharma has initiated clinical trials of GSNO in patients with asthma.
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  • Kevan Shokat, Ph.D.

    Synergy Between Investigators Opens New Approach to Asthma Chemical Biology, University of California, San Francisco

    As part of a broad approach to blocking the activation of inflammatory cells, Dr. Shokat discovered a drug that blocks the breakdown of GSNO, the very molecule that Dr. Stamler found to be reduced in asthma (above). The two investigators compared notes at the annual meeting of AAF investigators, and Dr. Shokat is now working with a former trainee of Dr. Stamler’s (now on the faculty of UCSF with Dr. Shokat) to develop this and other ways of preventing the loss of GSNO in asthma. Dr. Shokat has founded a company, Intellikine, which is actively pursuing these and other approaches to asthma.
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  • Jenny P-Y Ting, Ph.D.

    Newly Discovered Pathways to Inflammation Microbiology and Immunology, University of North Carolina at Chapel Hill

    A few years ago, Dr. Ting described a group of related proteins that are used throughout the animal and plant kingdoms to control immunity and inflammation. She called these CATERPILLER proteins, recently named NLR proteins. Her studies have led to the discovery of how these proteins work and their role in asthma. She has entered into an agreement with a major biotechnology company to apply this work to asthma therapies.
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  • Ralph Weissleder, Ph.D.

    Visualizing the Lungs During an Attack of Asthma Radiology, Harvard Medical School

    To better understand what causes asthma, it would be useful for scientists to see exactly what happens during asthma: how the airways close and open, what changes occur in the cells and fluids in airways, and what changes occur in the cells and enzymes that surround the airways. Dr. Weissleder is a leader in exploring new approaches to look at living tissue and, with his Award from the AAF, he has turned his attention to the asthmatic lung, bringing new understanding to the changes that occur in asthma. Dr. Weissleder has begun with studies of rodents, but his work will also have future application to humans with asthma.
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