EXTERNAL SEMINAR - El Cherif Ibrahim - Institut de Neuroscience de la Timone (INT)
Title: "Transcriptional signature of the major depressive episode"
Place & date: Campus of Luminy. TAGC, Seminar room TPR2-Bloc 5. Thursday, October 17th at 11h00.
The major depressive episode (MDE) affects nearly 15% of people worldwide. Its pathophysiology is still not completely understood but it involves systemic mechanisms and not just brain-restricted defects. So far, no biomarker of MDE has been validated and more than a third of patients do not respond to several lines of antidepressant treatment. We and others made the assumption that peripheral blood contain specific information about MDE dynamics, at the level of RNA expression, including small noncoding RNAs. Our aim is therefore to identify blood transcriptional signatures that distinguish MDE patients from controls and hopefully predict antidepressant response.
1: Apazoglou K, Farley S, Gorgievski V, Belzeaux R, Lopez JP, Grenier J, Ibrahim EC, El Khoury MA, Tse YC, Mongredien R, Barbé A, de Macedo CEA, Jaworski W,Bochereau A, Orrico A, Isingrini E, Guinaudie C, Mikasova L, Louis F, Gautron S,Groc L, Massaad C, Yildirim F, Vialou V, Dumas S, Marti F, Mechawar N, Morice E, Wong TP, Caboche J, Turecki G, Giros B, Tzavara ET. Antidepressive effects of targeting ELK-1 signal transduction. Nat Med. 2018 May;24(5):591-597. doi: 10.1038/s41591-018-0011-0. Epub 2018 May 7. PubMed PMID: 29736027.
2: Consoloni JL, Ibrahim EC, Lefebvre MN, Zendjidjian X, Olié E, Mazzola-Pomietto P, Desmidt T, Samalin L, Llorca PM, Abbar M, Lopez-Castroman J, Haffen E, Baumstarck K, Naudin J, Azorin JM, El-Hage W, Courtet P, Belzeaux R. Serotonin transporter gene expression predicts the worsening of suicidal ideation and suicide attempts along a long-term follow-up of a Major Depressive Episode. Eur Neuropsychopharmacol. 2018 Mar;28(3):401-414. doi:10.1016/j.euroneuro.2017.12.015. Epub 2017 Dec 27. PubMed PMID: 29287766.
3: Ibrahim EC, Guillemot V, Comte M, Tenenhaus A, Zendjidjian XY, Cancel A, Belzeaux R, Sauvanaud F, Blin O, Frouin V, Fakra E. Modeling a linkage between blood transcriptional expression and activity in brain regions to infer the phenotype of schizophrenia patients. NPJ Schizophr. 2017 Sep 7;3(1):25. doi: 10.1038/s41537-017-0027-3. PubMed PMID: 28883405; PubMed Central PMCID: PMC5589880.
4: Hervé M, Bergon A, Le Guisquet AM, Leman S, Consoloni JL, Fernandez-Nunez N, Lefebvre MN, El-Hage W, Belzeaux R, Belzung C, Ibrahim EC. Translational Identification of Transcriptional Signatures of Major Depression and Antidepressant Response. Front Mol Neurosci. 2017 Aug 8;10:248. doi: 10.3389/fnmol.2017.00248. eCollection 2017. PubMed PMID: 28848385; PubMed Central PMCID: PMC5550836.
5: Belzeaux R, Lin CW, Ding Y, Bergon A, Ibrahim EC, Turecki G, Tseng G, Sibille E. Predisposition to treatment response in major depressive episode: A peripheral blood gene coexpression network analysis. J Psychiatr Res. 2016 Oct;81:119-26. doi: 10.1016/j.jpsychires.2016.07.009. Epub 2016 Jul 9. PubMed PMID: 27438688.
6: Belzeaux R, Bergon A, Jeanjean V, Loriod B, Formisano-Tréziny C, Verrier L, Loundou A, Baumstarck-Barrau K, Boyer L, Gall V, Gabert J, Nguyen C, Azorin JM, Naudin J, Ibrahim EC. Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode. Transl Psychiatry. 2012 Nov 13;2:e185. doi: 10.1038/tp.2012.112. PubMed PMID: 23149449; PubMed Central PMCID: PMC3565773.
Internal Seminar - Julien Colle
Internal Seminar - Christine Brun
Internal Seminar - Quentin Ferre
Internal Seminar - Aïtor Gonzalez
Internal Seminar - Nathalie Lalevée
Internal Seminar - Andreas Zanzoni
Internal Seminar - David de Santiago Algarra
EXTERNAL SEMINAR - Pelin Sahlén - Science for Life Laboratory (Sweden)
Title: Understanding Atopic Dermatitis and Psoriasis variants using 3D conformation capture in differentiating human keratinocytes
Place: Campus of Luminy. TAGC, Seminar room TPR2-Bloc 5.
Atopic dermatitis (AD) and psoriasis are the two most common inflammatory disorders of the skin. Genome-wide association studies (GWAS) have pinpointed hundreds of variants, and the majority of them are located in noncoding regions, which impedes their functional interpretation. We differentiated primary normal epithelial keratinocytes and performed RNA-seq, ChIP-seq and capture Hi-C (HiCap) using a probe set targeting >20,000 promoters and GWAS variants associated with traits involving inflammatory skin diseases. Our study reveals coordinated regulation of differentiation genes by set of common enhancers, some also overlapping GWAS variants. We shed light on skin barrier component of psoriasis pathology and connect several dysregulated genes in AD and psoriasis lesions to GWAS variants. Several of these genes have not previously been implicated in AD or psoriasis and are plausible candidates for further studies.
*Sahlen, P. et al. Genome-wide mapping of promoter-anchored interactions with close to single-enhancer resolution. Genome Biol 16, 156 (2015).
*Anil, A. et al. HiCapTools: a software suite for probe design and proximity detection for targeted chromosome conformation capture applications. Bioinformatics 34, 675-677 (2018).
*Akerborg, O. et al. High-Resolution Regulatory Maps Connect Vascular Risk Variants to Disease-Related Pathways. Circ Genom Precis Med 12, e002353 (2019).
*Cavalli, M. et al. Allele specific chromatin signals, 3D interactions, and motif predictions for immune and B cell related diseases. Sci Rep 9, 2695 (2019).
*Zhang W. et al. The BAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 to Control ESC Differentiation, Cell Stem Cell 24, 138-152 (2019)