PHILADELPHIA — The Perelman School Medicine at the University of Pennsylvania has received a $12 million grant over five years from the National Institutes of Health to head up a multi-institutional study looking at the biology of asthma and other airway diseases. The goal of the research is to find new, druggable targets in the smooth muscles of the airway that could lead to more effective bronchodilators that prevent or reverse lung constriction for longer periods of time.

Current, long-term therapies for asthma keep the airways open for 12 hours to prevent attacks but at the same time desensitize a key cell surface receptor known as the G-coupled protein receptor (GCPR), limiting their efficacy.  Here, researchers will devise new therapeutics that sustain such receptors, and increase efficacy to 96 hours or more.

“Our approach has been to investigate novel targets and molecules with the hopes of finding bronchodilators that won’t lose activity and remain effective in severe asthma and other airway diseases, like COPD. We want longer-lasting treatment options,” said Reynold A. Panettieri, Jr, MD, director of the Asthma Section in the division of Pulmonary, Critical Care and Allergy, and Principal Investigator for the NIH grant. “This grant will propel our research even further, as the team, under the Airways Biology Initiative here at Penn, work towards much-needed and new approaches to managing asthma, a particular area of interest that affects 26 million Americans a year.”

Bronchodilators are medications that relax the bronchial muscles for obstructive lung diseases, like asthma.  Today, the disease costs the US about $56 billion in medical costs, lost work days, and even early deaths—some of which are caused by current medications.  COPD, or chronic obstructive pulmonary disease, costs the US almost $30 billion, not including lost productivity.

Past studies by researchers from the Initiative have uncovered new mechanisms in the airway smooth muscles that can be exploited. Recent studies in Science Translational Medicine and British Journal of Pharmacology , for instance, defined that regulators of G protein coupled signaling control smooth muscle contractile responses and promote smooth muscle cell growth—two findings that could serve as the basis for therapeutic targets in obstructive lung diseases.

The new research endeavor will elaborate on these discoveries and investigate other unique molecules that promote bronchodilation, new agonists to bitter taste receptors, and antagonists to GCPR to prevent bronchoconstriction.

Other institutions involved in the research include Thomas Jefferson University, the University of Southern Florida, Johns Hopkins University, and the University of Arkansas. The Program Project Grant (PPG) was awarded by the NIH’s National Heart, Lung and Blood Institute (1P01HL114471).

The PPG is more complex in scope and budget than the individual research grant. While individual research grants are awarded to support the work of one principal investigator who, with supporting staff, is addressing a scientific problem, program project grants are available to a group of several investigators with differing areas of expertise who wish to collaborate in research by pooling their talents and resources. PPGs represent synergistic research programs that are designed to achieve results not attainable by investigators working independently.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

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