Role of SREBP Network in Surfactant Lipid Homeostasis and Lung Maturation

Specific Aims: 1). Identify a transcriptional network controlling perinatal surfactant lipid homeostasis; 2). Determine the mechanisms by which SREBP influences perinatal lung lipid homeostasis; and 3) Determine the critical perinatal regulatory components in the SREBP network.

Collaboration with Drs. James Bridge, Jason Lu and Jeffrey Whitsett

"Lung Map" Atlas Research Center

Aims: 1) Cell and regional-specific nexgen rna analyses to create an "atlas" of gene expression in the murine lung during the canalicular/saccular/alveolar period. 2) Cell and regional-specific nexgen rna analyses to create an "atlas" of gene expression in human fetal lung during the canalicular/saccular/ alveolar period. 3) Systems biology/bioinformatics analysis of NEXGEN RNA sequences to define cell-specific gene expression during murine and human lung formation.

Role: Co-investigator

Multi-center collaborations (detail see Lungmap Roster)

Transcriptional Programming of Asthma Related Pathology in Respiratory Epithelia

Aims:1) Mechanisms controlling SPDEF expression and activity during mucus cell etaplasia; 2) Mechanisms by which SPDEF regulates mucus metaplasia and pulmonary inflammation; 3) regulation of innate immunity and lung function by SPDEF during Rhinoviral infection and aero-allergen exposure.

Role: Co-investigator

Role of SFTPC in Pathogenesis of Interstitial Lung Disease

This application tests the central hypothesis that environmental stress superimposed on a SFTPC mutation leads to accumulation of misfolded, cytotoxic SP-C that, in turn, results in Type II epithelial cell injury/death, which is the inciting event in SFTPC-associated familial ILD.

Role: Co-investigator

The Role of Autophagy in the Pathogenesis of interstitial Lung Disease

Aims: 1) Autophagy is an Important Cytoprotective Pathway for Turnover of Misfolded SP-C; 2) Identification of a Novel ER Quality Control Pathway Linked to Autophagy; 3) The Role of Autophagy in Pathogenesis of ILD.

Role: Co-investigator

Mechanisms of Dicer1 Function in Lung Organogenesis and Cystic Lung Disease

Aims: 1) Define developmental time periods and epithelial cell types wherein Dicer1 function is critical; 2) Determine the signaling pathways and miRNAs that are deregulated in Dicer1 deficient lungs; 3) Elucidate the role of Dicer1 haploinsufficiency and p53 loss in promoting mesenchymal growth.

Role: Co-investigator

Transcriptional Control of Submucosal Gland Formation and Function

Aims: 1) To define the role(s) of PAX9 in SMG formation and differentiation in vivo and in vitro; 2) To identify molecular mechanisms by which PAX9 interacts with transcriptional partners to regulate gene expression in SMGs; 3) To identify the role(s) of PAX9 and an associated gene network in the regulation of SMG formation and function in CF.

Role: Co-investigator

Airway Progenitor Cell Profileration and Differentiation During Lung Repair

Aims: 1) Transcriptional control of AEC progenitors, 2) production of antibodies against AEC progenitors, 3) transcriptional and genomic programming of AEC progenitors, and 4) generation and analysis of novel transgenic mouse models for study of proliferation, lineage analysis, homeostasis and repair in conducting airways.

Role: Co-investigator

Transcriptional networks and gene signatures for preterm birth via amniotic fluid transcriptome analysis.

Aims: 1). Identify the signature genes and tissue markers in normal full term and preterm fetus amniotic fluid; 2). Identify critical transcriptional regulators and targets associated with the preterm birth through transcriptional network analysis.

Collaboration with Drs. Beena Kamath-Rayne and Nathan Salomonis

Mechanisms Underlying DICER1 Suppression of Pleuropulmonary Blastoma

Role: Co-investigator

Single cell RNA-seq on Xenopus/mouse and human foregut cells at the time of Nkx2.1 induction

Role: Co-investigator