The primary goal of the Nicoli lab is to decode the in vivo requirements of miRNAs.  miRNAs are small non-coding RNAs that ensure precise protein output by targeting and degrading several messenger RNAs via an RNA recognition motif named the SEED sequence. Although miRNAs control more than 60% of gene expression, we still do not fully understand what the purpose of this regulatory mechanism is in vivo.  Major difficulties addressing this question include the recognition of phenotypes incurred by miRNA loss and the association of phenotypes to complex target gene networks.

We use vascular and neuronal development as a platform to dissect the function of the miRNA-regulome. We uniquely combine several experimental approaches to solve this biologic question including in vivo genomic manipulation of the zebrafish vertebrate system, single-cell resolution microscopy, live imaging of zebrafish development, and genome-wide computational analysis.
Why is this important?    

While changes in miRNA expression are a typical signature of cardiovascular and neurological disorders including atherosclerosis, diabetes and Alzheimer's disease, very little is known about the function of miRNAs in physiological processes. Placing miRNA function in tissue development and homeostasis will allow us to better understand the contribution of miRNAs to disease susceptibility and further predict the potential success of miRNA therapeutics. 


miRNAs and cardiovascular development

In our lab, we identified many miRNAs that are expressed in endothelial cells during vascular development, and generated over forty miRNA knockouts via CRISPR/Cas9 mutagenesis that are ready for phenotypic characterization. We are dissecting miRNA 
function in:

  • Hemogenic endothelium
  • Vascular angiogenesis
  • Vascular remodeling
  • Blood Brain Barrier

miRNAs and vascular cell homeostasis

 We identified the miRNA-mRNA interactome in human artery and vein endothelial cells by performing HITS-CLIP (high-throughput sequencing of RNAs isolated by crosslinking immunoprecipitation) for Argonaute2, the major RNA-binding protein that facilitates miRNA-mRNA interaction. We are interested in studying how and why endothelial miRNAs regulate specific vascular signaling pathways controlling:

  • Mechanotransduction
  • Cell Migration
  • Growth factors
  • Artery-Vein Identity