About Knipe Laboratory
Repetitive injury to the lung is believed to initiate many chronic lung diseases, including pulmonary fibrosis. The lung’s ability to repair normally depends on functional cellular processes involving epithelial cells, endothelial cells, immune cells, and fibroblasts. Ineffective repair leads to persistent tissue damage and fibrotic scarring. One example of inadequate repair in patients with pulmonary fibrosis is the failure of type 2 alveolar epithelial cells (AEC) to differentiate into type 1 AECs.
The Knipe Laboratory at Massachusetts General Hospital, led by Rachel Knipe, MD, is interested in understanding the mechanisms that lead to ineffective repair and fibrosis, focusing on the role of endothelial dysfunction in this process. We believe that persistent endothelial dysfunction activates fibroblasts and prevents epithelial regeneration after injury, thereby tipping the balance in the lung toward fibrosis rather than repair. We are interested in idiopathic pulmonary fibrosis (IPF) and fibrosis that occurs in the context of systemic diseases, such as connective tissue disease (CTD), and after viral infections, such as influenza or COVID-19 infections.
Endothelial cells are important for many tissue functions, with one primary role being modulating vascular permeability. The Knipe laboratory is interested in signaling pathways that regulate vascular permeability, including Rho kinase (ROCK) and sphingosine-1-phosphate (S1P). Both pathways induce significant cytoskeletal changes that influence endothelial barrier function. In addition, they mediate downstream signaling that controls migration, proliferation, and survival. The Knipe Lab has shown vital links between these signaling pathways and fibrotic outcomes in both bleomycin- and influenza-induced animal models of pulmonary fibrosis.
- Loss of endothelial S1PR1 drives post-influenza pulmonary fibrosis
- Activation of endothelial ROCK2 drives pulmonary fibrosis through increased vascular permeability
- Defining histologic and transcriptional changes in the lung endothelium that contribute to progressive pulmonary fibrosis
View Knipe Laboratoy publications
Awards and Recognitions
Rachel Knipe, MD, is supported by a Career Development Award from the NIH NHLBI (K08), awarded in 2018, and an NIH NHLBI R03, awarded in 2022. In 2021, she received the Eleanor Shore Fellowship Award from Harvard Medical School and Mass General Department of Medicine, and a Boehringer Ingelheim Discovery ILD Award. In 2022, she received the Jo Rae Wright Award from the American Thoracic Society Respiratory Cell and Molecular Biology Assembly.
- Rachel Knipe MD (PI)
- Patricia Brazee PhD (Post-Doctoral fellow)
- Trong Nguyen BS (Lab Manager)
- Roxene Clarke (Mouse Colony Manager)