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Role of epigenetic modifications in cardiovascular diseases: non-coding RNAs as regulators of smooth muscle cell activity in atherosclerosis and vascular inflammation
Italy (SISM) - Humanitas University, Milano
Dr. Leonardo Elia - Leonardo.Elia@humanitasresearch.it
Type of Research Project
- Basic science
What is the background of the project?
The role of epigenetics in vascular pathologies has been deeply investigated in the last decade. In particular, non- coding RNAs have arised as a new player in this field: micro RNAs (miRNAs) are a type of non-coding RNAs and they play a crucial role in vascular smooth muscle cell (VSMC), resident cells of vessels medial layer, whose deregulation correlates with vessel occlusion and vascular damage. Moreover, we have recently identified circular RNAs (circRNAs) as fine-tune modulatiors of miRNAs, partaking a role in VSMC biology and adding a new layer of knowledge in this field. Nonetheless, epigenetics panorama in vascular pathologies is wider and involves other processes such as the methilation of DNA and histone modifications. Such epigenetics changes are specifically studied in pathologies such as vascular aneurysm, atherosclerosis and re-stenosis, processes in which smooth muscle cells of the vessel walls play a pivotal, yet not fully understood, role. These pathological processes are responsible for the vast majority of cardiovascular diseases, from myocardial infarction and stroke to aortic aneurysm rupture, which are still the main causes of morbidity and mortality in western world; hence, a better understanding in the exact pathological processes may lead to new treatments and preventive strategies.
What is the aim of the project?
The aim of the project is to investigate the role of epigenetics in cardiovascular diseases in order to provide a new insight into molecular mechanisms underlying vessel damage.
What techniques and methods are used?
We will use a multidisciplinary approach based on different experimental techniques ranging from molecular to functional analysis. These approaches will be applied to both in vitro (primary VSMCs, cell lines) and in vivo models (murine models of vascular injury). In particular, as for the in vitro techniques, they will include RNA extraction from primary cells, retrotranscription by Polymerase Chain Reaction (PCR) in order to obtain copy DNA (cDNA), and quantitative PCR (qPCR) in order to assess specific target genes expression; we will conduct these analyses in both basal conditions and stimulated cells (growth factors and cytokines). Other techniques may be applied. Data analysis might be performed based on the amount of available data during the selected period.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
What are the tasks expected to be accomplished by the student?
By the end of this internship, we expect the students to be able to perform one or more techniques autonomously, being capable to analyze and interpret the data. In details, the student will first shadow the researchers as they show and teach him how to perform the techniques mentioned above (RNA extraction, retro-transcription, quantification via PCR); then the student will be allowed to perform such techniques with the supervision of the researcher, provided that enough attention and interest is demonstrated during the previous phase. All the produced data and the reason for the experiment in the setting of the project will be discussed by the researcher with the student so that he keeps track of what is being done and why.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Please see the references section. Further informations will be provided during the internship. Protocols regarding each technique that the student will see will be provided, as well as any kind of useful material. Moreover, the student will be able to attend to general scientific and research seminars periodically organised by Humanitas University during his stay; the dates and times of these seminars will be provided during the internship as soon as published by the University (usually 1 week in advance)
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Knowledge of basic lab safety rules is mandatory. Any previous lab experience is well seen. Additionally, the student should be truly interested in cardiovascular research.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system
- TGFβ Triggers miR-143/145 Transfer From Smooth Muscle Cells to Endothelial Cells; Thereby Modulating Vessel Stabilization. Montserrat Climent; Manuela Quintavalle; Michele Miragoli; Ju Chen; Gianluigi Condorelli; and Leonardo Elia. Circ Res. 2015 May 22;116(11):1753- 64. doi: 10.1161/CIRCRESAHA.116.305178. Epub 2015 Mar 23.
- Leonardo Elia; Paolo Kunderfranco; Pierluigi Carullo; Marco Vacchiano; Floriana Maria Farina; Ignacio Fernando Hall; Stefano Mantero; Cristina Panico; Roberto Papait; Gianluigi Condorelli; Manuela Quintavalle. UHRF1 epigenetically orchestrates smooth muscle cell plasticity in arterial disease. J Clin Invest. 2018 Jun 1;128(6):2473-2486. doi: 10.1172/JCI96121. Epub 2018 May 7.
- Leonardo Elia and Gianluigi Condorelli. RNA (Epi)genetics in cardiovascular diseases. J Mol Cell Cardiol. 2015 Dec;89 (Pt A):11-6. doi: 10.1016/j.yjmcc.2015.07.012. Epub 2015 Jul 20.
- Elia Leonardo; Quintavalle Manuela. Epigenetics and Vascular Diseases: Influence of Non-coding RNAs and Their Clinical Implications. Front Cardiovasc Med. 2017 Apr 27;4:26. doi: 10.3389/fcvm.2017.00026. eCollection 2017.
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