Disrupting Six/Eya Signalling as New Therapy for Lung Fibrosis
Abstract
This proposal will address the Fiscal Year 2018 Peer Reviewed Medical Research Program topic area of Pulmonary Fibrosis and Respiratory Health. Lung diseases are currently the third killer in the United States, behind cancer and cardiovascular conditions, yet there is a lack of effective therapies for lung diseases. Among lung diseases, lung fibrosis is a common condition. A defining feature of lung fibrosis is shortness of breath that is a result of the lung being unable to oxygenate blood effectively. This happens as a result of scarring in the alveolar spaces, which obliterates these airspaces where oxygen is able to diffuse into the red blood cells and oxygenate the body. Although we now understand the environmental, workplace, and genetic predispositions that may lead to lung fibrosis, many of the mechanisms that promote and maintain this aberrant repair process are not known. There are very limited treatment options for patients with lung fibrosis, which accounts for approximately 50% of all lung transplantations. This highlights the need to develop new treatments for lung fibrosis. Novel findings have identified a molecule known as Sineoculis homeobox homolog 1 or Six1 to be elevated in patients with lung fibrosis. Six1 is only normally observed in the embryo where it plays a role in the development of the lungs, therefore its presence in adult lungs with lung fibrosis is abnormal. Remarkably, Six1 was observed to be present in lung epithelial cells from patients with IPF. Experiments aimed at investigating whether Six1 could be a novel target for lung fibrosis demonstrated that switching off Six1 in lung cells was able to halt the progression of experimental lung fibrosis. These important findings allow us to hypothesize that pharmacological or gene therapy aimed at disrupting Six1 in the lungs could provide novel therapies for lung fibrosis. These experiments will be tested in this proposal, and if successful, they will pave the way for new treatments for lung fibrosis.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910007
Entities
People
- Harry Karmouty-Quintana
Organizations
- United States Army
- University of Texas Health Science Center at Houston