Qin Ma, PhD, FAIMBE, and Mingtao Zhao, DVM, PhD, were recently awarded a four-year R24 grant from the National Institutes of Health (NIH) to deepen the understanding of the genetic basis behind cardiac development and disease in those with Down syndrome, a genetic condition caused by an extra copy of chromosome 21, called trisomy 21.
The interdisciplinary research study, titled “Single-Cell and Spatial Atlas of Human and Mouse Trisomy 21 Hearts,” combines Drs. Ma and Zhao’s expertise with that of co-investigator Sanjeev S. Ranade PhD, assistant professor in the Center for Cardiovascular and Muscular Diseases at Sanford Burnham Prebys. Their work will advance perceptions on congenital heart disease by pairing multimodal single-cell and spatial profiling with an integrated AI and computational framework. Using human patient-derived induced pluripotent stem cells (iPSCs) alongside mouse, zebrafish, and pig models, the study will generate a harmonized cross-species atlas and build predictive, mechanism-level models of trisomy 21 cardiac development. The study will:
- Examine how trisomy 21 disrupts early heart development and contributes to the structural heart defects that affect approximately half of individuals with the condition.
- Combine iPSCs, genetically engineered mouse models and cutting-edge single-cell and spatial transcriptomics to examine heart development at unprecedented cellular resolution, with the aim to uncover the cellular and tissue mechanisms that drive congenital heart defects in Down syndrome.
- Develop and publicly share the first open-access, single-cell and spatial atlas of human and mouse trisomy 21 hearts through the INCLUDE Experimental Models of Down Syndrome (EMODS) portal, which is expected to support researchers worldwide by accelerating discoveries into the causes of congenital heart defects in Down syndrome and advancing future biomedical research.
- Bring together experts in artificial intelligence, biomedical science and computational biology to develop innovative methods for analyzing complex biological data and accelerating discoveries that improve human health.
The study has the potential to unravel the regulatory mechanisms underpinning complex diseases such as Down syndrome, providing new insights into the genetic and developmental processes underlying them.
