Stefania Nicoli, Ph.D.
Yale Cardiovascular Research Center
Department of Internal Medicine
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.
1)Lopez-Ramirez MA, Calvo CF, Ristori E, Thomas JL, Nicoli S. (2016) Isolation and Culture of Adult Zebrafish Brain-derived Neurospheres. J Vis Exp. Feb 29;(108). PMID: 26967835
2)Ristori, E., Lopez-Ramirez, M.A., Narayanan, A., Hill-Teran, G., Calvo, C.F., Thomas, J.L. and Nicoli, S. (2015) A dicer-miR107 interaction regulates biogenesis of specific miRNAs crucial for neurogenesis. Dev Cell. 32, 546–560. PMID 25662174
Description: This paper finds that miR-107 controls by negative feedback loop DICER and the biogenesis of miRNAs to allow the formation of an exact number of neurons in development. Embryos lacking miR-107-dicer regulation have developmental megalencephaly due to unexpected augmentation of neurons in the brain.
3)Baeyens, N., Nicoli, S., Coon, B.G, Ross, D., Van den Dries, K., Han, J., Lauridsen, H.M., Mejean C., Eichmann, A., Thomas, J.L., Humphrey, J.D. and Schwartz, M.A. (2015) Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point. eLife. 04645. PMID 25643397
4)Fortuna, V., Pardanaud, L., Brunet, I., Nicoli*, S. and Eichmann*, A. (2015) Vascular mural cells promote noradrenergic differentiation of sympathetic neurons in zebrafish embryos. Cell Reports. 11, 1–11. *Co-senior author. PMID 26074079
Description: This paper described an unprecedented role played in vivo by endothelia cells and hemodynamic fluid in recruiting smooth muscle cells (SMC). Flow-dependent recruitments and maturation of SMC is detrimental in development to allow differentiation and function of the sympathetic neurons that control blood vessels innervation.
5)Ristori, E. and Nicoli, S. (2015) miRNAs expression profile in zebrafish developing vessels. Methods Mol Biol. 1214, 129-50. PMID 25468601
Description: In this paper we described strategies optimized in our lab to isolate miRNAs from small amounts of endothelia cells. We mastered the preparation small RNA libraries suitable for Illumina Deep Sequencing.
Lab URL: http://nicolilab.com
Emma Ristori, MS. Associate Researcher
Dionna Kasper, Ph.D. Postdoctoral Fellow
Albertomaria Moro, Ph.D. Postdoctoral Researcher
Hanna Mandl Undergraduate Student
Meredith Cavanaugh, MS. Fish Facility Manger