Stefania Nicoli, PhD
Associate Professor TenureCards
About
Titles
Associate Professor Tenure
Director of the Zebrafish Phenotyping Core for Precision Medicine, Internal Medicine and Genetics; Co-Director, Yale Cardiovascular Research Center (YCVRC)
Appointments
Cardiovascular Medicine
Associate Professor TenureFully JointGenetics
Associate Professor TenureFully JointPharmacology
Associate Professor TenureSecondary
Other Departments & Organizations
- Cardiovascular Medicine
- Center for RNA Science and Medicine
- Genetics
- Internal Medicine
- Molecular Cell Biology, Genetics and Development
- Molecular Medicine, Pharmacology, and Physiology
- Nicoli Lab
- Pharmacology
- Vascular Biology and Therapeutics Program
- Yale Cardiovascular Research Center (YCVRC)
- Yale Combined Program in the Biological and Biomedical Sciences (BBS)
- Yale Stem Cell Center
- Yale Ventures
- YCCEH
Education & Training
- Postdoctoral Fellow
- University Massachusetts Medical School (2011)
- PhD
- University of Brescia (2007)
- BS
- University of Milan (2002)
Research
Overview
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.
Medical Subject Headings (MeSH)
Academic Achievements and Community Involvement
Links & Media
Media
- MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos
- Cartoon representing the miR-107-dicer interaction to keep miR-9 level across the hindbrain ventricular zone
- Zebrafish Vascular-Mural-Noradrenergic unit. Green: Endothelial cells; Blue: Sympathetic Neurons; Red: Smooth Muscle Cells
News
- July 11, 2024
Protein Detects and Responds to Changes in Blood Flow
- July 18, 2023Source: Technology Networks
Study Reveals New Insights on Blood Stem Cell Diversity
- July 17, 2023Source: YaleNews
Study Sheds Light on Origins, Changeability of Blood Stem Cells
- March 13, 2023
Meet Lauren Thornton, BS, PhD Candidate (Nicoli Lab)