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INFORMATION FOR

Stefania Nicoli, PhD

Associate Professor Tenure; Director of the Zebrafish Phenotyping Core for Precision Medicine, Internal Medicine and Genetics; Co-Director, Yale Cardiovascular Research Center (YCVRC)

Research Summary

Using Zebrafish, my laboratory's goal is to understand how small non-coding RNAs coordinate cardiovascular and neuronal development.

Extensive Research Description

The vascular system is fundamental for embryonic development and adult life, and aberrant vascularization is associated with numerous diseases, including cancer,atherosclerosis and stroke. Since the processes that govern blood vessel formation are conserved, it is possible to use model systems to gain novel insights on vascular development and function. The Zebrafish (Danio rerio) is an ideal model to study blood vessel formation during embryonic development. The transparency and external development of the zebrafish embryo allow an unprecedented level of observation and experimental manipulation. In parallel, numerous techniques allow forward and reverse genetic analysis of signaling pathways in the zebrafish.These genetic approaches coupled with the ability to easily visualize circulatory patterns and blood vessel morphology, make the zebrafish an ideal in vivo platform to assay gene function during vascular development.

microRNAs (miRNAs) are highly conserved non-coding small RNAs that post-transcriptionally regulate gene expression by binding to the 3’UTR of target mRNAs and inhibit their translation, or promote their degradation. miRNAs are autonomously transcribed in a large mRNA transcript (pri-mRNA), or are found in introns of coding genes. In both cases,mature miRNAs are formed by sequential processing into a primary stem loop precursor (pre-miRNAs) by the endonucleases Drosha and Dicer. In vertebrates,the 22 base pair duplex miRNAs are unwound and a single mature strand is loaded onto Argonaute 2 (Ago2). The Ago2/miRNA complex (the RNA-induced silencing complex, or RISC), leads to translational repression and decreased transcript stability, through deadenylation. miRNAs function in a number of different biological processes, including cardiogenesis, muscle development, oncogenesis, brain morphogenesis, and hematopoiesis.

Despite recent findings, several critical barriers remain that hamper the study of miRNAs. First, identification of relevant miRNA targets, especially cell-specific target transcripts in vivo,can be difficult. Second, genetic manipulation (i.e. targeted knockout) of miRNA sequences in the vertebrate genome can be challenging and, until recently, had been limited to mice. Third, in many cases loss of miRNA function leads to subtle phenotypic changes, which can be difficult to observe and characterize during embryonic stages in mouse. Finally, the genetic interaction of miRNAs and their targets can be difficult to dissect in vivo in the mouse system.

The lab takes advantage of the zebrafish as a model system to overcome these barriers. Our goal is to elucidate how miRNAs participated in the genetic network driving arteries-veins differentiation, angiogenesis, neuro-vascular development.


Coauthors

Research Interests

Blood-Brain Barrier; Cardiovascular System; Neurons; Zebrafish; MicroRNAs

Research Images

Selected Publications

  • 3089 – WNT AND NOTCH SIGNALING REGULATION IN PRE-HEMOGENIC ENDOTHELIUM CONTROL HEMATOPOIETIC STEM AND PROGENITOR CELLS HETEROGENEITY.Ghersi J, cheng L, Luff S, Sturgeon C, Baldissera G, Hintzen J, Nicoli S. 3089 – WNT AND NOTCH SIGNALING REGULATION IN PRE-HEMOGENIC ENDOTHELIUM CONTROL HEMATOPOIETIC STEM AND PROGENITOR CELLS HETEROGENEITY. Experimental Hematology 2022, 111: s89. DOI: 10.1016/j.exphem.2022.07.145.
  • Chapter 15 Comparative Functions of miRNAs in Embryonic Neurogenesis and Neuronal Network FormationRistori E, Nicoli S. Chapter 15 Comparative Functions of miRNAs in Embryonic Neurogenesis and Neuronal Network Formation 2017, 265-282. DOI: 10.1016/b978-0-12-804402-5.00015-7.
  • Heparin Derivatives and Semisynthetic Biotechnological Heparins as Angiogenesis InhibitorsPresta M, Leali D, Stabile H, Ronca R, Camozzi M, Moroni E, Nicoli S, Liekens S, Marco L. Heparin Derivatives and Semisynthetic Biotechnological Heparins as Angiogenesis Inhibitors 2012, 371-391. DOI: 10.2174/978160805205910502010371.
  • Erratum: MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesisNicoli S, Standley C, Walker P, Hurlstone A, Fogarty K, Lawson N. Erratum: MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis Nature 2010, 467: 356-356. DOI: 10.1038/nature09412.
  • Fibroblast Growth Factor-2 in AngiogenesisPresta M, Mitola S, Dell'Era P, Leali D, Nicoli S, Moroni E, Rusnati M. Fibroblast Growth Factor-2 in Angiogenesis 2008, 77-88. DOI: 10.1007/978-0-387-71518-6_7.
  • Heparin Derivatives and Semisynthetic Biotechnological Heparins as Angiogenesis InhibitorsPresta M, Leali D, Stabile H, Ronca R, Camozzi M, Moroni E, Nicoli S, Liekens S, Rusnati M. Heparin Derivatives and Semisynthetic Biotechnological Heparins as Angiogenesis Inhibitors Frontiers In Medicinal Chemistry - Online 2005, 2: 371-391. DOI: 10.2174/1567204052931087.