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1. Wnt介導的調節體細胞重編程和多能性的機制。

Cosma實(shí)驗室發(fā)現，Wnt / -catenin信號通路的激活增強了細胞融合介導的多種體細胞的重編程（Lluis et al.,Cell Stem Cell 2008； Stem Cell 2010）。另外，團隊提出Tcf3通過(guò)在重編程過(guò)程中大幅調節表觀(guān)基因組修飾來(lái)充當體細胞重編程潛力的阻遏物（Lluis et al., PNAS 2011； Ombrato et al., Cell Cycle 2012）。此外，Wnt信號通路的波動(dòng)控制著(zhù)mESC多能性的維持，并且對于重編程至關(guān)重要（Marucci et al., Cell Reports 2014； Aulicino et al., Stem Cell Reports 2014； Arumugam et al., Cell Reports 2020）。最近的研究還顯示，Wnt活性調節mESCs中的細胞周期并維護mESCs穩定性（De Jaime-Soguero et al., Plos Genetics 2017；Theka et al., Scientific Reports 2019）。此外，本團隊發(fā)現了干細胞染色質(zhì)結構及其與多能性的相關(guān)性（Ricci et al.,Cell 2015； Neguembor et al., NAR 2018）。

2. 細胞間融合以在哺乳動(dòng)物中再生組織。

我們研究了細胞間融合（Sottile et al., Cell Reports 2017）和倍性維持（Frade et al., Science Advances 2019）的機制。結果表明，骨髓（BM）細胞與退化的小鼠視網(wǎng)膜中的視網(wǎng)膜神經(jīng)元和穆勒膠質(zhì)細胞可融合。體內形成的雜合子在視網(wǎng)膜變性的藥物誘導和遺傳模型中進(jìn)行神經(jīng)元重編程和再生（Sanges et al., Cell Reports 2013； J.of Clinical Investigation 2016； Pesaresi et al., eBiomedicine 2018）。此外，我們還發(fā)現，BM衍生的雜合子可以在兩種帕金森氏病小鼠模型（Altarche-Xifro et al., eBiomedicine 2016）中拯救多巴胺能神經(jīng)元的功能，并在肝切除術(shù)后再生小鼠肝臟（Pedone et al., Cell Reports 2017）。最后，我們最近確定了受損的人和小鼠視網(wǎng)膜釋放的趨化因子，進(jìn)而定義了趨化因子與受體的相互作用，以增強移植細胞向小鼠視網(wǎng)膜的遷移和整合（Pesaresi et al., Molecular Therapy，2020）。

3. 染色質(zhì)結構及其3D空間排列的超分辨率識別。

Cosma實(shí)驗室使用超高分辨率熒光顯微鏡（隨機光學(xué)重建顯微鏡； STORM）在體細胞和干/重編程細胞中解剖了核小體組裝體的納米級組織（Lakadamyali et al.,Nature Method 2020年）。確定了一種新型的染色質(zhì)纖維結構模型，以及解碼后的結構與多能性之間的關(guān)系（Ricci et al.,Cell 2015）。最近還將組蛋白尾巴乙?；绾斡绊懠{米級DNA緊縮可視化，并鑒定了位于離核小體中心的特定納米級區域內的DNA簇（Otterstrom et al.,NAR 2019）。另外，團隊還研究了干細胞中組蛋白的動(dòng)態(tài)變化（Gomez-Garcia et al.,Cell report 2021）。開(kāi)發(fā)了STAC和PoSTAC標記策略，可對非重復序列和基因組動(dòng)力學(xué)進(jìn)行快速成像，并對細胞空間組織進(jìn)行超分辨率成像（Neguembor et al.,NAR 2018）。此外，使用逆向工程方法，我們研究了調控轉錄網(wǎng)絡(luò )（Cantone et al.,Cell 2009），并在研究轉錄的基本機制方面取得了突破性的發(fā)現（Cosma et al.,Molecular Cell 2001； Cosma et al.,Cell 1999）。

2003   EMBO青年研究員獎

2005   瑪麗居里杰出成就獎

2007   意大利共和國爵士等級勛章

2010   ICREA 研究教授

2010   EMBO會(huì )士

2016   巴塞羅那城市獎

2018   中國國家重大人才項目

Neguembor, MV, Castells-Garc a A, Martin L, Vicario, C, G mez-Garc a, PA, AlHaj Abed, J, Granados, A, Sebastian-Perez, R, Sottile, F, Solon, Wu, CT, Lakadamyali, L, and Cosma MP (2021). Transcription-mediated supercoiling regulates genome folding and loop formation. Molecular Cell, July 22 online. https://doi.org/10.1016/j.molcel.2021.06.009

Gomez‐Garcia PA, Portillo‐Ledesma S, Neguembor MV, Pesaresi M, Oweis W, Rohrlich T, Wieser S, Meshorer E, Schlick T, *Cosma MP, and *Lakadamyali M. (2021) Mesoscale modeling and single nucleosome tracking reveal remodeling of clutch folding and dynamics in stem cell differentiation. Cell Reports *co-last and co-corresponding authors. 12 January 2021, 108614

Pesaresi M, Bonilla-Pons SA, Sebastian-Perez R, Di Vicino U, Alcoverro-Bertran M, Michael R and Cosma MP (2021). The chemokine receptors, Ccr5 and Cxcr6, enhance the integration of mesenchymal stem cells into the degenerating retina. Molecular Therapy. 3 February 2021, Pages 804-821

Arumugam K, Shin W, Schiavone V, Tu T, Romo R, Paull E, Subramaniam P, Worley J, Califano C, Cosma  MP (2020). The Master Regulator protein BAZ2B can reprogram human hematopoietic lineage-committed progenitors into a multipotent state. Cell Reports, Dec 8;33(10):108474.

Aulicino F, Sottile F, Pedone E, Lluis F, Marucci M and Cosma MP (2020). Canonical Wnt pathway controls mESCs self-renewal through inhibition of spontaneous differentiation via -catenin/TCF/LEF functions (2020). Stem Cell Reports, Sept. 8, Issue 3, 646-661

Lakadamyali, M and Cosma, M.P (2020). Visualizing the genome in high resolution challenges our textbook understanding. Nature Methods, 17, 371–379

Frade J, Nakagawa S, Cortes P, di Vicino U, Romo N, Lluis F and Cosma MP (2019). Controlled ploidy reduction of pluripotent 4n cells generates 2n cells during mouse embryo development. Science Advances, Vol. 5, no. 10, 16 Oct 2019

Otterstrom J, Castells Garcia A, Vicario C, *Cosma MP, *Melike Lakadamyali M. Super-resolution microscopy reveals nucleosomal level decompaction of chromatin upon hyperacetylation. (2019) Nucleic Acid Research, *co-last and co-corresponding authors

Pesaresi, M, Bonilla S, Simonte G, Sanges D, Di Vicino U, and Cosma MP (2018). Endogenous mobilization of bone-marrow cells into murine retina induces fusion mediated reprogramming of M ller glia cells. eBioMedicine. 30 (2018) 38–51

Neguembor MV, Sebastian-Perez R, Aulicino F, Gomez-Garcia PA, *Cosma MP, and *Lakadamyali M (2018). PoSTAC (Polycistronic SunTAg modified CRISPR) enables live-cell and super resolution visualization of multiple genes. Nucleic Acids Res. Mar 16;46(5):e30.*co-corresponding authors.

De Jaime-Soguero A, Aulicino F, Ertaylan G,  Grieco A, Cerrato A, Tallam A, del Sol A,  *Cosma MP and *Lluis F and (2017). Wnt/b-catenin/Tcf1 pathway controls mouse embryonic stem cell cycle progression and proliferation by regulating the Ink4/Arf locus. Plos Genetics. Mar 27;13(3). *co-last and co-corresponding authors

Pedone E, Oltenau VA, Marucci L, Mu？oz-Martin MI, Youssef SA, de Bruin A, and Cosma MP (2017). Modeling Dynamics and Function of Bone Marrow Cells in Mouse Liver Regeneration. Cell Reports, 18, 107–121

Sanges D, Simonte G DiVicino U, Romo N, Pinilla I, Nicol s Farr s M and Cosma MP (2016). Reprogramming Mu？ller glia via in vivo cell fusion regenerates murine photoreceptors Journal of Clinical Investigation, Aug 1;126(8):3104-3116

Ricci MA, Manzo C, Garc a-Parajo M, *Lakadamyali M, and *Cosma MP (2015). Chromatin fibers are formed by heterogeneous groups of nucleosomes in vivo. Cell, Mar 12;160(6):1145-58. *co-last authors. Nominated F1000Prime 2015

https://www.youtube.com/watch?v=5KSr-giy8qo

Marucci L, Pedone E, Di Vicino U, Sanuy-Escribano B, Isalan M, and Cosma MP. Beta-Catenin fluctuates in mouse ESCs and Is essential for Nanog-mediated reprogramming of somatic cells to pluripotency (2014). Cell Reports, Sep 25;8(6):1686-96.

Sanges D, Romo N, Simonte G, Di Vicino U, Tahoces AD, Fern ndez E, Cosma MP. (2013) Wnt/ -Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina. Cell Reports Jul 25;4(2):271-86.

Lluis F, Ombrato L, Pedone E, Pepe S, Merrill BJ, Cosma MP. (2011)  T-cell factor 3 (Tcf3) deletion increases somatic cell reprogramming by inducing epigenome modifications. PNAS Jul 19;108(29):11912-7.

Polito V and Cosma MP (2009). IDS crossing of the blood-brain barrier corrects CNS defects in MPSII mice. American Journal of Human Genetics Aug;85(2):296-301.

Cantone I, Marucci L, Iorio F, Ricci MA, Belcastro V, Bansal M, di Bernardo M, Santini D, di Bernardo D and Cosma MP (2009). A yeast synthetic network for In-vivo assessment of reverse-engineering and modelling approaches. Cell Apr 3;137(1):172-81

Lluis F, Pedone E, Pepe S, Cosma MP (2008). Periodic activation of Wnt/b-catenin signalling enhances somatic cell reprogramming mediated by cell fusion. Cell Stem Cell. Nov 6;3(5):493-507