1. Wnt介导的调节体细胞重编程和多能性的机制。

Cosma实验室发现，Wnt / -catenin信号通路的激活增强了细胞融合介导的多种体细胞的重编程（Lluis et al.,Cell Stem Cell 2008； Stem Cell 2010）。另外，团队提出Tcf3通过在重编程过程中大幅调节表观基因组修饰来充当体细胞重编程潜力的阻遏物（Lluis et al., PNAS 2011； Ombrato et al., Cell Cycle 2012）。此外，Wnt信号通路的波动控制着mESC多能性的维持，并且对于重编程至关重要（Marucci et al., Cell Reports 2014； Aulicino et al., Stem Cell Reports 2014； Arumugam et al., Cell Reports 2020）。最近的研究还显示，Wnt活性调节mESCs中的细胞周期并维护mESCs稳定性（De Jaime-Soguero et al., Plos Genetics 2017；Theka et al., Scientific Reports 2019）。此外，本团队发现了干细胞染色质结构及其与多能性的相关性（Ricci et al.,Cell 2015； Neguembor et al., NAR 2018）。

2. 细胞间融合以在哺乳动物中再生组织。

我们研究了细胞间融合（Sottile et al., Cell Reports 2017）和倍性维持（Frade et al., Science Advances 2019）的机制。结果表明，骨髓（BM）细胞与退化的小鼠视网膜中的视网膜神经元和穆勒胶质细胞可融合。体内形成的杂合子在视网膜变性的药物诱导和遗传模型中进行神经元重编程和再生（Sanges et al., Cell Reports 2013； J.of Clinical Investigation 2016； Pesaresi et al., eBiomedicine 2018）。此外，我们还发现，BM衍生的杂合子可以在两种帕金森氏病小鼠模型（Altarche-Xifro et al., eBiomedicine 2016）中拯救多巴胺能神经元的功能，并在肝切除术后再生小鼠肝脏（Pedone et al., Cell Reports 2017）。最后，我们最近确定了受损的人和小鼠视网膜释放的趋化因子，进而定义了趋化因子与受体的相互作用，以增强移植细胞向小鼠视网膜的迁移和整合（Pesaresi et al., Molecular Therapy，2020）。

3. 染色质结构及其3D空间排列的超分辨率识别。

Cosma实验室使用超高分辨率荧光显微镜（随机光学重建显微镜； STORM）在体细胞和干/重编程细胞中解剖了核小体组装体的纳米级组织（Lakadamyali et al.,Nature Method 2020年）。确定了一种新型的染色质纤维结构模型，以及解码后的结构与多能性之间的关系（Ricci et al.,Cell 2015）。最近还将组蛋白尾巴乙酰化如何影响纳米级DNA紧缩可视化，并鉴定了位于离核小体中心的特定纳米级区域内的DNA簇（Otterstrom et al.,NAR 2019）。另外，团队还研究了干细胞中组蛋白的动态变化（Gomez-Garcia et al.,Cell report 2021）。开发了STAC和PoSTAC标记策略，可对非重复序列和基因组动力学进行快速成像，并对细胞空间组织进行超分辨率成像（Neguembor et al.,NAR 2018）。此外，使用逆向工程方法，我们研究了调控转录网络（Cantone et al.,Cell 2009），并在研究转录的基本机制方面取得了突破性的发现（Cosma et al.,Molecular Cell 2001； Cosma et al.,Cell 1999）。

2003   EMBO青年研究员奖

2005   玛丽居里杰出成就奖

2007   意大利共和国爵士等级勋章

2010   ICREA 研究教授

2010   EMBO会士

2016   巴塞罗那城市奖

2018   中国国家重大人才项目

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