Unraveling the mechanisms of asthma
On World Asthma Day, we applaud the innovative and translational lung research conducted by our BIO5 Institute members.
Asthma, a condition of narrowed airways and excess mucus in the lungs, affects more than 25 million people in the U.S., including more than 6 million under the age of 18. By investigating the causes and identifying molecular markers of asthma, researchers at the BIO5 Institute help scientists and physicians to better prevent, identify and treat this chronic lung condition.
Those with asthma often experience shortness of breath, coughing, wheezing and chest tightening. Symptoms can range in severity and frequency, though colds, exercise, workplace conditions or allergies can cause symptoms to flare. Asthma attacks more often affect adult women and young children, but in general, the condition interferes with everyday life activities and contributes to the permanent narrowing of the bronchi in many patients.
There is no cure for asthma, but symptoms can be managed with preventive, long-term medications to reduce airway inflammation and narrowing.
BIO5 members including former director Fernando Martinez developed the oldest research center in the College of Medicine into the robust and outcome-focused Asthma & Airway Disease Research Center (A2DRC) to address these gaps in knowledge.
“UArizona has a long tradition of research in respiratory diseases, but at A2DRC, we wanted to focus on new ways to prevent and treat asthma and chronic pulmonary disease,” Martinez said. “An important part of our current work is to understand how exposure to protective bacteria in early life can prevent the development of asthma and allergies.”
Two major collaborative studies led from the Center are addressing this issue: the Binational Early Asthma and Microbiome Study (BEAMS) that is comparing exposures to bacteria and development of the immune system in Nogales Sonora and Tucson Arizona; and the Oral Bacterial Extracts for the Prevention of Wheezing and Asthma (ORBEX) clinical trial, in which over 800 children aged less than 18 months from all over the US are receiving bacterial products or placebo, to determine if these products can gear the immune system against the development of asthma.
Allergens, infections, and a family history of asthma can place an individual at risk for disease, but the exact links to asthma are unknown. To better decipher the disease etiology, Darren Cusanovich, assistant research scientist and professor at BIO5, studies how genetic variation and environmental exposures alter the regulation of our genetic code and ultimately lead to chronic disease. Because asthma involves complex interactions between many cell types of the lung and immune system, Cusanovich uses single-cell genomics to understand the impact of genetic and environmental variability.
Cusanovich originally trained with Donata Vercelli, professor of cellular and molecular medicine and director of molecular genomics at A2DRC. Vercelli, also the director of the Arizona Center for the Biology of Complex Diseases, works at the interface of immunology and genetics in complex lung diseases. She’s well known for devising a highly innovative approach to combine multiple basic science and public health methods to understand the mechanisms behind the asthma-protective and asthma-promoting effects of two distinct U.S. farming environments.
Since many aspects of the innate immune response to allergies and infectious agents are dysfunctional in asthma, Monica Kraft, chair of the Department of Medicine, aims to understand the relationship between infection and body’s response. Kraft, also a physician-scientist in the Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, has more than 150 publications in the areas of adult asthma and lung remodeling, as well as devised clinical trials to evaluate new therapies for asthma patients.
Mucus overproduction is a hallmark of almost all chronic airway disease including asthma, but mechanical suction remains the only therapy. Associate professor in the College of Pharmacy Yin Chen investigates the regulation of mucus production to better understand disease progression and ultimately identify targeted therapies.
Chen, Vercelli, Martinez, and collaborators including BIO5 member Deepta Bhattacharya were also awarded a $2.58 million grant from the National Institute of Allergy and Infectious Diseases (NIAID) to better understand asthma caused by exposure to fungi.
Dr. Martinez, a Regents’ Professor, and Stefano Guerra, director of population science at the A2DRC, are highly regarded for their work on the natural history of asthma. Dr. Guerra combines the powers of patient specimens with epidemiologic and phenotypic approaches to identify risk factors, disease prevalence and novel biomarkers. Dr. Martinez is world-renowned for his work on the natural history, genetics and treatment of childhood asthma.
Using the biomarkers identified by Drs. Martinez and Guerra, collaborator Julie Ledford, associate professor of cellular and molecular medicine and clinical translational sciences, seeks to determine the mechanistic roles for these biomarkers. Further, Ledford, also an associate professor of immunobiology and medicine, studies the genetic and molecular mechanisms for allergic airway diseases in children.