Modulation of hedgehog signaling in tobacco-related emphysema

While a great number of people are exposed to tobacco smoke, only a small percentage of those people go on to develop tobacco-related lung diseases such as emphysema, suggesting that different people might have different susceptibility to tobacco exposure. Multiple genetic studies have identified variations near a gene called Hedgehog-interacting protein (HHIP) that predisposes people to developing emphysema. Despite the known association between variations in this and related genes and emphysema, very little is known about how it might influence emphysema development. Our proposal aims to define the role of HHIP and related genes in the development of emphysema, providing therapeutic rationale for targeting this molecular pathway in patients with emphysema to improve the prognosis of this debilitating tobacco-related lung disease.