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Defining the Role of Hedgehog Signaling in Emphysema

Institution: University of California, San Francisco
Investigator(s): Chaoqun Wang, Ph.D. in Biomedical Sciences
Award Cycle: 2019 (Cycle 28) Grant #: 28FT-0012 Award: $180,996
Subject Area: Pulmonary Disease
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. Emphysema is a subtype of COPD, characterized by enlargement of the air sacs of the lungs. There is still no effective cure for emphysema due to the incompletely understood disease process. People have different susceptibility to emphysema and this has been associated with the differences in individual genetic background. Previous studies have implicated deficiency in a gene called hedgehog interacting protein (HHIP) in emphysema and reduced production of HHIP was observed in emphysema lungs, suggesting that the activity of this gene protects against emphysema. However, we are still unclear about how HHIP is involved in emphysema. Our preliminary studies support the hypothesis that loss of HHIP causes emphysema. We will define HHIP's role in modulating the molecular pathway called hedgehog (Hh) and test the effect of an FDA-approved Hh inhibitor on emphysema. Furthermore, we will define the role of HHIP in mediating critical interactions between different cell types, using lung cells from healthy individuals and from patients with emphysema. Successful completion of this proposal would provide important insights on how molecular abnormalities contribute to emphysema, and therapeutic rationale to FDA-approved Hh inhibitors trial in patients with emphysema.