2006

2005-2006

Richard T. Strait, MD, Cincinnati Children's Hospital Medical Center, “Inhibition of immunopathology by blocking antibodies” (NIAID Referral).

 Prevention of severe allergies by use of 'allergy shots' is a common practice, but the reasons the shots only sometimes work is not well understood. Since early in the 20th century scientists have suspected that one possible explanation for why allergy shots might improve allergy symptoms is through serial exposure to just small enough amounts of the substance that set off the allergy, thus causing the body to develop antibodies that neutralize the offending substance before it can cause allergy symptoms. However, the existence of these 'blocking antibodies' has never been proven. Dr. Strait's investigations have proven their existence by using a mouse model of severe allergic reaction. This research has demonstrated that certain antibodies can be made by the body and neutralize an allergic substance by two methods. One is by interception before it can reach certain target cells in the body and second by once the substance does reach these certain cells, binding to the substance and a receptor on that target cell that blunts the allergic reaction of that cell to the substance. Thus, scientists now have definitive proof of the existent of blocking antibodies and have two different target mechanisms to work with in designing better allergy shots. AAFA is pleased to note that as a result of the progress made during the AAFA grant, Dr. Strait's investigations were published in a peer-reviewed scientific journal (The Journal of Clinical Investigation Volume 116, Number 3, March 2006).

2004-2005

Anthony A. Horner, MD, University of California, San Diego, “Analysis of airway-TLR ligand interactions and their impact on CD4 cell differentiation.”  (NHLBI referral) 

In addition to allergens, there are a variety of environmental factors that are likely to influence the development of allergic asthma.  For instance, microbes such as bacteria, viruses, and fungi – which are present almost everywhere – have a profound effect on how our immune systems work.  Researchers are currently focusing their efforts to describe just exactly what these microbial effects are and how they are related to asthma and allergies.  This research project contributes to this effort.  We have found that airway exposure in a mouse to bacterial peptidoglycan promotes the development of allergies and asthma, while airway exposure to bacterial DNA prevents this development.  Given that there are high levels of both bacterial peptidoglycan and bacterial DNA in air and dust samples, the goal of our research project is to understand why these two bacterial products seem to have such opposite effects.

2003-2004

David Lewis, MD, Stanford University School of Medicine, “Mechanisms of viral induced asthma:  role of TH1 cytokines and dendritic cells.”   (NIAID Referral)

Dr. Lewis's laboratory is interested in determining how respiratory viral infections may increase the risk of allergic sensitization and allergic diseases, such as asthma. His group has developed a mouse model in which mice sequentially are infected with influenza A virus, the most common cause of the annual flu, and then sensitized and challenged starting 30 days later with allergens. The results from the first year of funding have found that influenza A infection augments later allergen sensitization and asthmatic inflammation. The mechanism involves, in part, alterations in the function and increases in the number of lung dendritic cells following influenza infection. Dendritic cells are key in either turning on or turning off immune responses to allergens. A major surprise is that these alterations in dendritic cells and the enhancement of later allergic disease requires the production of a cytokine called interferon-gamma. Interferon-gamma has been widely accepted as potentially limiting allergic diseases, but it is clear that its effects on allergy are dependent on the context and the timing of its production. These findings have potentially important clinical implications as to the design of immunotherapy for asthma that utilizes Th1 cytokines, such as interferon-gamma, and also suggest that more universal vaccination for influenza of young children might be beneficial in reducing the onset of allergic disease in those who are genetically predisposed.

2003

Vincenzo Casolaro, MD, Johns Hopkins Asthma and Allergy Center, “Regulation of IL-4 cells involved in allergic disease”   (NIAID Referral)

2002-2003

Amy Simon, MD, Tufts University School of Medicine, “The role of the Jak-STAT pathway in airway remodeling”  (NHLBI Referral)

2001-2002

David Corry, MD, Baylor College of Medicine, “The role and mechanisms of action of the cytokine, IL-13, in the lung”  (NHLBI Referral)

2001

Dr. Juan José Lafaille, New York University School of Medicine, “In vivo regulation of IgE production” (NIAID Referral)

2000

Gurjit Khurana Hershey, MD, PhD, Children’s Hospital Research Foundation, “Biology of IL-4 Receptor Allelic Variants”  (NIAID Referral)

1999-2000

Giovanni Piedimonte, M.D., Director, University of Miami School of Medicine, “Neurogenic Inflammatory Response to RSV”   (NIAID Referral)

Thomas F. Huff, PhD, Virginia Commonwealth University, “Differentiation of Mast Cells In Vitro”  (NIAID Referral)

Thomas F. Huff, Ph.D., Virginia Commonwealth University, and his team examined the relationship of mast cell to the bone marrow stem cell, from which it grows. The mast cell's granules and IgE receptors explain how they become the major effector cell in asthma and allergic disease. His laboratory discovered a unique form of a DNA-binding protein, called GATA-2, which controls expression of the genes for some of the granule proteins or IgE receptor proteins, and therefore the mast cell's function. His team thinks that this shorter form of GATA-2 might be useful as a novel means of allergy therapy by inhibiting the mast cell granules and IgE receptors. In another mast cell project, his laboratory studied telomerase. Telomerase prevents cells from aging, and has been called the "fountain-of-youth" gene. Most cells do not express telomerase, but the laboratory has found that mast cells, like bone marrow stem cells, do express telomerase. His team has also studied whether this expression of telomerase is associated with the mast cell's unique ability to divide.