researchers

Danopoulos, Soula Athanasia PHD

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

INCLUDE Grants

Type I IFN signaling during lung development in Down Syndrome-Multiome sequencing of human fetal and pediatric trisomy 21 lungs

Danopoulos, Soula Athanasia

Trisomy 21 (T21) is the most prevalent chromosomal abnormality worldwide, with an incidence of approximately 1 in 700 live births. Our single cell RNAseq data and immunofluorescent stainings have demonstrated upregulation of the surfactant metabolism pathway and increased cell number of differentiated proximal airway markers (SCGB1A1 and FOXJ1), suggesting precocious development/differentiation in the T21 lungs, which may be associated to genome wide perturbation due to dysregulated epigenetic regulation. In this proposal we will assess the ontogeny of pulmonary anomalies observed in Down Syndrome (DS) by using single nuclear (sn) RNA and snATAC sequencing (multiome sequencing) to simultaneously assess the epigenetic landscape and determine the cellular and molecular abnormalities observed in developing T21 lungs (from prenatal to postnatal), which may ultimately provide a foundation for potentially new therapies for compromised lungs in individuals with DS.

Type I interferon regulates angiogenesis in Down Syndrome

Al Alam, DeniseDanopoulos, Soula Athanasia

Down Syndrome (DS), often due to Trisomy 21 (T21), is the most prevalent chromosomal abnormality worldwide, [1, 2] resulting in several pulmonary disorders such as pulmonary hypertension and hemosiderosis, both possibly caused by a dysregulated lung endothelium. While endothelial cell defects in T21 have been described, a detailed understanding of lung specific endothelial defects and the mechanisms underlying these anomalies during human lung development remains elusive. A detailed understanding of the role of type I interferon pathway in endothelial cell defects in the human developing lung can lead to the discovery of novel therapeutic targets not only for DS but also other lung diseases where endothelial cells defects are observed, such as pulmonary hypertension and alveolar capillary dysplasia.