教育

1991.10-1993.06本科，化學與製藥技術，那不勒斯費德裏克二世大學

1993.10-1993.12碩士學位，化學與製藥技術，那不勒斯費德裏克二世大學

1995.10-2000.10博士學位，細胞與分子遺傳學，那不勒斯費德裏克二世大學

工作

1997.11-2000.05瑪麗居裏獎學金，分子病理學研究所(IMP)，博士後，從事分子病理學研究。

2000-2003那不勒斯Telethon遺傳與醫學研究所(TIGEM)，助理研究員，從事分子病理學研究。

2003-2010那不勒斯Telethon遺傳與醫學研究所(TIGEM)，副研究員，從事分子病理學研究。

2004-2010歐洲分子醫學院(SEMM)，講師。

2009-2012那不勒斯遺傳與生物物理研究所(IGB)，榮譽副研究員，從事分子病理學研究。

2010-2018巴塞羅那基因調控中心(CRG)，研究教授和高級研究員，從事分子病理學研究。

2018年至今：中國科學院廣州生物醫藥與健康研究所(GIBH)，研究員，從事哺乳動物中控製體細胞重編程和組織再生的影響因子及其相關機製的研究.

1. Wnt介導的調節體細胞重編程和多能性的機製。

Cosma實驗室發現，Wnt /β-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通過在重編程過程中大幅調節表觀基因組修飾來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信號通路的波動控製著mESC多能性的維持，並且對於重編程至關重要（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中的細胞周期並維護mESCs穩定性（De Jaime-Soguero et al., Plos Genetics 2017；Theka et al., Scientific Reports 2019）。此外，本團隊發現了幹細胞染色質結構及其與多能性的相關性（Ricci et al.,Cell 2015；Neguembor et al., NAR 2018）。

2.細胞間融合以在哺乳動物中再生組織。

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）的機製。結果表明，骨髓（BM）細胞與退化的小鼠視網膜中的視網膜神經元和穆勒膠質細胞可融合。體內形成的雜合子在視網膜變性的藥物誘導和遺傳模型中進行神經元重編程和再生（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元的功能，並在肝切除術後再生小鼠肝髒（Pedone et al., Cell Reports 2017）。最後，我們最近確定了受損的人和小鼠視網膜釋放的趨化因子，進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膜的遷移和整合（Pesaresi et al., Molecular Therapy，2020）。

3.染色質結構及其3D空間排列的超分辨率識別。

Cosma實驗室使用超高分辨率熒光顯微鏡（隨機光學重建顯微鏡；STORM）在體細胞和幹/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纖維結構模型，以及解碼後的結構與多能性之間的關係（Ricci et al.,Cell 2015）。最近還將組蛋白尾巴乙酰化如何影響納米級DNA緊縮可視化，並鑒定了位於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，團隊還研究了幹細胞中組蛋白的動態變化（Gomez-Garcia et al.,Cell report 2021）。開發了STAC和PoSTAC標記策略，可對非重複序列和基因組動力學進行快速成像，並對細胞空間組織進行超分辨率成像（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絡（Cantone et al.,Cell 2009），並在研究轉錄的基本機製方麵取得了突破性的發現（Cosma et al.,Molecular Cell 2001；Cosma et al.,Cell 1999）。

2003EMBO青年研究員獎

2005瑪麗居裏傑出成就獎

2007意大利共和國爵士等級勳章

2010ICREA研究教授

2010EMBO會士

2016巴塞羅那城市獎

2018中國國家重大人才項目

Neguembor, MV, Castells-García A, Martin L, Vicario, C, Gómez-García, PA, AlHaj Abed, J, Granados, A, Sebastian-Perez, R, Sottile, F, Solon, Wu, CT, Lakadamyali, L, andCosma MP(2021).Transcription-mediated supercoiling regulates genome folding and loop formation.MolecularCell, 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 andCosma 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, ShinW, Schiavone V, Tu T, Romo R, Paull E, Subramaniam P, WorleyJ, Califano C,CosmaMP(2020). The Master Regulator protein BAZ2B can reprogramhuman 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 andCosma MP(2020).Canonical Wnt pathway controls mESCs self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions (2020).Stem Cell Reports, Sept. 8, Issue 3, 646-661

Lakadamyali, M andCosma, 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, LluisF andCosma 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, andCosma MP(2018). Endogenous mobilization of bone-marrow cells into murine retina induces fusion mediated reprogramming of Müller 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 MPand *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, andCosma 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, Nicolás Farrés M andCosma MP(2016). Reprogramming Mu？ller glia via in vivo cell fusion regenerates murine photoreceptorsJournal of Clinical Investigation, Aug 1;126(8):3104-3116

Ricci MA, Manzo C,García-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, andCosma MP. Beta-Catenin fluctuates in mouse ESCs and Is essential for Nanog-mediatedreprogramming 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, Fernández E,Cosma MP. (2013) Wnt/β-Catenin Signaling Triggers Neuron Reprogramming and Regeneration in the Mouse Retina.Cell ReportsJul 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.PNASJul 19;108(29):11912-7.

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

Cantone I, Marucci L, Iorio F, Ricci MA, Belcastro V, Bansal M, di Bernardo M, Santini D, di Bernardo D andCosma MP(2009).A yeast synthetic network for In-vivo assessment of reverse-engineering and modelling approaches.CellApr 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