Role of GPR116 in Alveolar Homeostasis
The major goals of this project are to define the signaling pathways by which GPR116 controls surfactant homeostasis using cell-based assays and mouse genetics through completion of three integrated aims: 1) Defining the signaling pathways downstream of activated GPR116; 2) In vivo activation of endogenous GPR116 to reverse alveolar surfactant overload; 3) Defining the pathogenesis of pulmonary disease induced by epithelial-drive surfactant overload.
9/1/16 – 8/31/23
(PI: Whitsett; Co-I:Bridges)
Editing Alveolar Progenitor Cells for Correction of Monogenic Disease
Aims: Seeks to develop novel strategies designed to use CRISPR/CAS9 gene editing for lung progenitor cells for correction of a prototypic Childhood Interstitial Lung Diseases (CHILD) disorder that disrupts pulmonary surfactant homeostasis (ABCA3 deficiency) that leads to fatal infantile lung disease.
(PI: Miller; Co-I:Bridges)
Mechanisms of vGPCR mediated Cytomegalovius growth in the salivary gland.
The major goals are to define the mechanisms by which CMV vGPCRs signal through Gaq/Ga11 proteins leading to altered salivary gland physiology ultimately affecting CMV growth and spread. In Aim 1, knockout mice deleted for Gaq and Ga11 will be studied for their ability to support MCMV replication in the salivary gland. In Aim 2, changes in gene expression in murine salivary glands will be examined. In Aims 3 and 4 murine and human salispheres will be used to study the biochemical and function activities of the MCMV and HCMV vGPCRs. The data gleaned from these studies will provide novel insight into the mechanisms that regulate HCMV replication in the gland and provide a basis for future intervention of these processes.