Damien Saulep-Easton

Publications

• 7.48

  Impact points

  Analysis of microRNA turnover in mammalian cells following Dicer1 ablation.

  Michael P Gantier, Claire E McCoy, Irina Rusinova, Damien Saulep, Die Wang, Dakang Xu, Aaron T Irving, Mark A Behlke, Paul J Hertzog, Fabienne Mackay, Bryan R G Williams

  Nucleic acids research. 03/2011; 39(13):5692-703.

  Although microRNAs (miRNAs) are key regulators of gene expression, little is known of their overall persistence in the cell following processing. Characterization of such persistence is key to the full appreciation of their regulatory roles. Accordingly, we measured miRNA decay rates in mouse embryo... [more] Although microRNAs (miRNAs) are key regulators of gene expression, little is known of their overall persistence in the cell following processing. Characterization of such persistence is key to the full appreciation of their regulatory roles. Accordingly, we measured miRNA decay rates in mouse embryonic fibroblasts following loss of Dicer1 enzymatic activity. The results confirm the inherent stability of miRNAs, the intracellular levels of which were mostly affected by cell division. Using the decay rates of a panel of six miRNAs representative of the global trend of miRNA decay, we establish a mathematical model of miRNA turnover and determine an average miRNA half-life of 119 h (i.e. ∼5 days). In addition, we demonstrate that select miRNAs turnover more rapidly than others. This study constitutes, to our knowledge, the first in-depth characterization of miRNA decay in mammalian cells. Our findings indicate that miRNAs are up to 10× more stable than messenger RNA and support the existence of novel mechanism(s) controlling selective miRNA cellular concentration and function.
• 10.05

  Impact points

  B-cell stage and context-dependent requirements for survival signals from BAFF and the B-cell receptor.

  Fabienne Mackay, William A Figgett, Damien Saulep, Melanie Lepage, Margaret L Hibbs

  Immunological reviews. 09/2010; 237(1):205-25.

  One remarkable feature of the immune system is its capacity to maintain constant numbers of resting immune cells despite the complex nature of signals needed throughout development and maturation. For many years, B-cell survival was thought to rely solely on B-cell receptor (BCR) tonic signals that ... [more] One remarkable feature of the immune system is its capacity to maintain constant numbers of resting immune cells despite the complex nature of signals needed throughout development and maturation. For many years, B-cell survival was thought to rely solely on B-cell receptor (BCR) tonic signals that would trigger necessary basal survival pathways. The discovery of the tumor necrosis factor (TNF)-like ligand BAFF(B-cell activating factor belonging to the TNF family)/BLyS (B-lymphocyte stimulator) changed these views entirely, as BAFF-deficient mice lack most mature B cells, and treatment with BAFF inhibitors leads to their loss, establishing BAFF as an unappreciated key B-cell survival factor. BAFF-mediated survival signals have been mapped and signaling crosstalk with the BCR has been identified, explaining the need for both BCR- and BAFF-mediated signals for B-cell survival. However, this crosstalk only explains how BCR and BAFF signals cooperate to produce survival proteins and yet, inactivating pro-apoptotic factors such as FOXO proteins, which may be managed separately by BAFF and the BCR, has emerged as an equally important step for survival. In this review, we present new views on B-cell survival, at all stages of B-cell life, and suggest that, in most cases, survival results from the production of appropriate survival factors balanced with the adequate and timely degradation of pro-apoptotic proteins.
• 6.37

  Impact points

  B-cell tolerance breakdown in Sjögren's syndrome: focus on BAFF.

  Marie-Michèle Varin, Laëtitia Le Pottier, Pierre Youinou, Damien Saulep, Fabienne Mackay, Jacques-Olivier Pers

  Autoimmunity reviews. 05/2010; 9(9):604-8.

  Sjögren's syndrome (SS) is an autoimmune epithelitis hallmarked by a destruction of epithelial cells, the subsequent lymphocytic infiltration of exocrine glands and their ensuing dryness. Given the prominent role currently assigned to B cells in SS, it is not surprising that the B cell activatin... [more] Sjögren's syndrome (SS) is an autoimmune epithelitis hallmarked by a destruction of epithelial cells, the subsequent lymphocytic infiltration of exocrine glands and their ensuing dryness. Given the prominent role currently assigned to B cells in SS, it is not surprising that the B cell activating factor belonging to the Tumor Necrosis Factor family (BAFF) is involved in its pathogenesis. When overexpressed, this cytokine leads to self-reactive B cells emergence at the transitional B-cell stage. BAFF overexpression that has been observed in SS, is associated with B-cell tolerance breakdown and autoantibody production. Furthermore, BAFF is responsible for the abnormal distribution of B cells subsets and B-cell hyperactivity described in the blood. In the salivary glands, a minority of B-cell clusters represent ectopic germinal center cells, while the majority manifest features consistent with transitional type 2 (T2) and marginal-zone (MZ)-like B cells. Interestingly, both types of B-cell cluster include autoreactive B cells and BAFF is associated with expansion of T2 B cells and MZ-like B cells in the salivary glands. Finally, BAFF plays a major role in B-cell repopulation after their depletion by rituximab in SS.