Research Project: The pluripotency factor OCT4 in pulmonary fibrosis
basic biologic mechanisms
interstitial lung disease
The lung is critical for gas exchange between the body’s blood vessels and the outside air, facilitating both removal of carbon dioxide from and uptake of oxygen by the body. The structure of lung tissue is similar to a honeycomb, maximizing surface area for gas exchange. In the deadly disease idiopathic pulmonary fibrosis (IPF), the lung accumulates excessive scar tissue. This impairs gas exchange. I am studying why scar tissue accumulates in lung fibrosis and its link with inflammation. I will focus on cells known as myofibroblasts, which produce most of the excessive scar tissue. Initial findings show elevated levels of the gene Oct4 in myofibroblasts in IPF lung cells. Additionally, deletion of Oct4 in a pool of progenitor cells (descendents of stem cells) dramatically protects against fibrosis. Using human and mouse fibrotic lung samples, I am studying mechanisms underlying the protective effect of this Oct4 deletion. This work promises to identify novel targets that will be helpful in developing new treatments to combat lung fibrosis.
We identified Oct4 as a regulator of the disease-causing fibroblast precursors in pulmonary fibrosis. Additionally, when Oct4 activation is blocked, pulmonary fibrosis is prevented in a model of pulmonary fibrosis. We found Oct4 deletion led to a reduction in a protein called CCN1, which is involved in inflammation and fibroblast activation. Blockade of CCN1 reduces inflammatory cells and fibroblasts in a mouse model of pulmonary fibrosis. We are now studying how Oct4 and CCN1 are linked to promote fibrosis.