One of the main goals of Ranade lab is to understand how cellular signaling is connected to cellular differentiation in development. Specifically, we study how cardiopharyngeal neural crest cells integrate into the heart and craniofacial structures by receiving signaling cues from pharyngeal progenitor cells. This crosstalk is required for proper organ morphogenesis and is the origin for some congenital developmental defects in complex syndromic disorders such as Down Syndrome. We primarily use human pluripotent stem cell and mouse models of development and disease to address these questions.
Signaling and Differentiation in Heart and Craniofacial Development
In our previous work, we have developed an unbiased and temporal profile of the transcriptional and chromatin accessibility states of single cells in early stages of mouse heart development. This work allowed us to pinpoint specific subsets of cardiac and neural crest progenitor cells impacted due to loss of transcription factors or in the context of aneuploidy.
In our future work, we will build on this foundation by:
- Developing new mouse models driven by enhancers for specific cellular populations
- Using spatial transcriptomics to map the locations and states of progenitor cells
- Developing new image-based machine learning algorithms to find hidden connections between cellular location and cellular state/fate
Functional Interrogation of Epigenetic Regulatory Elements
In our past work, we generated novel machine learning algorithms that could predict transcriptional enhancer potential of open chromatin regions in the genome for both cardiac and neural crest cells. One major outstanding question now is to understand how the regulatory elements controlling differentiation programs are activated by signaling factors. We are currently using high throughput perturbations with CRISPR based modulations and activity reporter assays to define how cis regulatory elements controlling developmental programs are impaired in the context of developmental disorders.