Asthma & Allergic Diseases Research

Joshua A. Boyce, MD

Asthma and allergic diseases are among the most common serious medical conditions in the developed world. The objective of the Asthma and Allergic Disease Research Center is to develop state of the art, collaborative, multidisciplinary approaches to understanding the basic environmental, genetic, and mechanistic aspects of asthma and allergic diseases. These approaches will permit more efficient translation of novel research findings into new approaches to the diagnosis and treatment of these diseases. The Center is composed of investigators from several disciplines, with backgrounds in basic cellular and molecular immunology, biostatistics, genetics, functional genomics, pulmonary physiology, and clinical trials.

Basic/Laboratory Research

A large percentage of the basic research is carried out at the Inflammation and Allergic Disease Research Section in the Division of Rheumatology, Immunology and Allergy. This Section has a more than a 40-year history of accomplishment in the discovery of mechanisms of asthma and allergic disease. The Section is also noteworthy for having trained many leaders in the field of academic allergy and immunology through its NIH-funded fellowship training program. The Section is co-directed by K. Frank Austen, MD, and Joshua A. Boyce, MD. The core faculty conduct basic and translational research that is focused entirely on the mechanisms of asthma and allergic disease. The faculty includes three full Professors, four Associate Professors, four Assistant Professors, and eight Instructors. The faculty includes leading investigators in the areas of eicosanoid biology, mast cell biology, and mechanisms of inflammation. The investigators have developed several cellular, molecular, and whole animal experimental systems to study the basic mechanisms that cause asthma and allergic disease, and as a result have identified several molecular targets for drug development. The advent of two new classes of medications for asthma within the last decade, 5-lipoxygenase inhibitors and leukotriene receptor antagonists, resulted largely from the work done by the investigators in the Section. Several of the faculty members are MDs who are clinically active in addition to their laboratory responsibilities. The scientific program of the Section is supported largely by grants from the National Institutes of Health (NIH). There is also an NIH-funded training grant that supports a total of 9 fellows in allergy and immunology, with a major educational mission to train future leaders in the field of basic research in asthma and allergy.

Clinical Research

Clinical research in the Center has focused on the development of new approaches to the treatment of life-threatening allergic reactions (anaphylaxis) to cancer chemotherapy drugs. These approaches, developed by Dr. Mariana Castells, involve the administration of very small doses of the offending drug to the patient, followed by successively larger and larger doses until the desired therapeutic dose is achieved. This procedure, referred to as “desensitization”, has now been safely carried out on over 300 patients with cancer at the BWH and is now being widely adopted by other institutions. There is collaboration with the laboratory researchers to understand the mechanism by which desensitization works. There are clinical trials of newly developed drugs for the treatment of allergic diseases. These include anti-IL-5 (a treatment for a rare, potentially lethal disorder known as the hypereosinophilic syndrome), bradykinin receptor antagonists (for the treatment of hereditary angioedema) and anti-IgE (for the treatment of food allergies). These studies are generally funded by the pharmaceutical industry.

The clinical investigators of the Section collaborate actively with those in the Pulmonary Division at the BWH through their activities in the Partners Asthma Center, a major referral center devoted to the diagnosis and care of patients of all ages with asthma. The Asthma Center includes an Asthma Clinical Research Center under the direction of Dr. Elliot Israel, a principal investigator on the NIH-funded Asthma Clinical Research Network. The Research Center provides staff and expertise in running clinical trials and performing procedures such as bronchoscopy, spirometry, and inhalation challenge studies for research purposes.

Research in the Genetics of Allergic Diseases at the Channing Laboratory: Respiratory, Environmental and Genetic Epidemiology Division

The Respiratory Division of the Channing Laboratory was founded in 1972 by Frank Speizer, MD. It has a long history of excellence in research related to the environmental and genetic causes of asthma. Currently the Division is led by Scott T. Weiss, MD, and has a faculty of 27 investigators and 110 support staff. The asthma genetics program is maintained by grants from the NIH. The research expertise of the division is divided into several research programs: asthma pharmacogenetics (in collaboration with the BWH Pulmonary Division), asthma genetics, asthma genetical genomics (whole genome gene expression) in the mouse and the human, high throughput genotyping and gene expression, environmental exposure assessment, predictive medicine, and immunoepidemiology. There are strong links to animal model researchers for mouse asthma and mouse genetics of asthma. The Channing Laboratory respiratory division expertise is highly complimentary to that of the Inflammation and Allergic Diseases Section and hence provides synergy for the Center.