Modeling and understanding alveolar hypoplasia in Down syndrome using iPSCs-derived alveolar type II cells
Grant Award Details
Grant Type:
Grant Number:
DISC0-15654
Investigator(s):
Name:
Type:
PI
Disease Focus:
Human Stem Cell Use:
Award Value:
$1,524,196
Status:
Pre-Active
Grant Application Details
Application Title:
Modeling and understanding alveolar hypoplasia in Down syndrome using iPSCs-derived alveolar type II cells
Public Abstract:
Research Objective
Understanding alveolar progenitor cell defects in T21 and the genes/pathways associated with them will allow for developing therapeutic approaches for individuals with DS.
Impact
Although trisomy 21 affects multiple organ system, respiratory complications are the major cause of death in kids and adults with DS. The causes of lung disease in DS remain poorly understood.
Major Proposed Activities
Understanding alveolar progenitor cell defects in T21 and the genes/pathways associated with them will allow for developing therapeutic approaches for individuals with DS.
Impact
Although trisomy 21 affects multiple organ system, respiratory complications are the major cause of death in kids and adults with DS. The causes of lung disease in DS remain poorly understood.
Major Proposed Activities
- Create an in vitro model to study alveolar defects in Trisomy 21 using T21 and euploid iPSCs lines
- Elucidate the defects in progenitor cell commitments to AT2 and AT1 cells in Trisomy 21
- Determine the role of the FGFR2 pathway in such defects and whether targeting this pathway in ex vivo organoid model can reverse the defects observed in T21
Define the role of the mesenchymal niche in the alveolar hypoplasia phenotype observed in T21- Generate unique resources (iPSCs) from diverse racial and ethnic background that will become available to the scienti<c community to study other co-morbidities of DS (intestine, pancreas, liver)
- Generate multi-omics data that will be made publicly available and serve as a tool for other scientist to develop other research questions
Statement of Benefit to California:
In California, about 667 babies are born with Down Syndrome every year, with the highest DS rate for Hispanic infants. Respiratory complications are the most common cause for hospital admissions in DS. Healthcare cost is 12-13 times higher for children with Down Syndrome than those without. Understanding lung disease in Down Syndrome provides the opportunity to intervene early and adequately thus ameliorating outcomes and reducing healthcare burden for the state of California.