Laboratorio de Dinámica Intracelular

Nuestro grupo se especializa en la aplicación de diversas técnicas avanzadas de microscopía de fluorescencia (por ejemplo, FCS, SMT, SPT, microscopías SIM, confocal, multifotón y espectral), con el fin de visualizar procesos biológicos relevantes en células vivas y analizarlos de forma cuantitativa. Mediante este tipo de estudios es posible, por ejemplo,registrar en tiempo real el movimiento de biomoléculas individuales y sus interacciones con otras biomoléculas o componentes celulares, permitiendo obtener mayor información sobre los mecanismos involucrados en los procesos biológicos en comparación con los datos que se obtienen con métodos convencionales; en los cuales se promedia el comportamiento de un gran número de biomoléculas y muchas veces en contextos artificiales como lo es un tubo de ensayo. Con esta estrategia experimental, colaboramos con diversos grupos de investigación en Argentina y en el exterior aplicando estas metodologías para buscar responder preguntas muy variadas en los campos de la biología celular, la biología molecular y la biofísica.

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Our lab specializes in the application of diverse advanced fluorescence microscopy techniques (for example, FCS, SMT, SPT, SIM, confocal, multiphoton, and spectral microscopy) to visualize biologically relevant processes in living cells and analyze them quantitatively. Through this kind of studies, it is possible, for example, to track the motion of individual biomolecules in real time and their interactions with other biomolecules or with cellular components. This allows us to gain more information about the mechanisms involved in biological processes compared with conventional methods, in which the behavior of a large number of biomolecules is averaged, often in artificial contexts such as a test tube. Using this experimental strategy, we collaborate with many research groups in Argentina and abroad, applying these methodologies to answer a wide range of questions in the fields of cell biology, molecular biology, and biophysics.

Regulación de la transcripción: relevancia de los condensados transcripcionales

Exploramos los mecanismos moleculares involucrados en la regulación de la expresión de genes, lo cual es fundamental para comprender propiedades biológicas emergentes como la identidad celular, y procesos relevantes incluyendo el desarrollo y el envejecimiento, así como el desarrollo de ciertas enfermedades como el cáncer.

Como sistemas modelos, estudiamos los factores de transcripción (TFs) de pluripotencia, los cuales son esenciales para la preservación de células madre embrionarias en estado indiferenciado, y el receptor de glucocorticoides, un TF que se activa por unión a glucocorticoides, los cuales son muy empleados como fármacos por sus efectos antiinflamatorios. En particular, buscamos responder las siguientes preguntas:

• Qué función cumplen los condensados transcripcionales? Estos compartimentos sin membrana concentran TFs y otras moléculas relacionadas con la transcripción y sus funciones son aún poco claras.
• ¿Cuáles son los mecanismos involucrados en las respuestas tempranas de células madre a una señal de diferenciación?
• ¿Cómo afectan las fuerzas mecánicas al programa transcripcional? Las células están expuestas constantemente a fuerzas de sus vecinas o de la matriz extracelular que se transmiten al interior del núcleo. Estas fuerzas cumplen un papel esencial durante las primeras etapas del desarrollo, y dirigen las decisiones de destino celular de células madre.
• ¿Cuál es el rol de la arquitectura del genoma en la regulación transcripcional? El genoma humano se pliega en el espacio formando diversos tipos de estructuras, pero no está claro que papel cumple esta organización tridimensional en la activación de genes.

Organización dinámica del citoesqueleto y su función en la transmisión de señales mecánicas

Estudiamos cómo diversas redes que conforman el citoesqueleto (microtúbulos, filamentos de actina y filamentos intermedios) pueden generar, transmitir y responder a las señales mecánicas, tanto intracelulares como aquellas provenientes del exterior, influyendo en el comportamiento y destino celular.

Transporte intracelular mediado motores moleculares

Exploramos los principios que regulan el transporte intracelular conducido por los motores moleculares dependientes de microtúbulos (kinesina y dineína) y de filamentos de actina (miosina) y su relación con el microentorno celular. Buscamos caracterizar cómo las fuerzas físicas ejercidas por los motores -en conjunto con el citoesqueleto- son capaces de condicionar la distribución espacial de organelas como así también inducir la deformación de aquellas de mayor tamaño.

En particular, nos focalizamos en caracterizar la dinámica mitocondrial. Las mitocondrias son organelas esenciales para la supervivencia celular y su correcto posicionamiento en el citoplasma asegura la ocurrencia de diversos procesos biológicos. Empleando como sistemas modelos células melaóforas de Xenopus laevis y la línea celular U2OS, buscamos responder las siguientes preguntas:

¿Cómo es la dinámica intracelular de las mitocondrias? Las mitocondrias son organelas que exhiben diversas morfologías dependiendo del tipo celular o del estado metabólico de las células. Pueden presentar formas esféricas, elongadas o formar complejas redes interconectadas, lo cual repercute en su dinámica e interacción con el sistema de transporte.

¿Cómo las fuerzas mecánicas ejercidas por los motores moleculares y el citoesqueleto modulan la morfología de las mitocondrias? El correcto funcionamiento de estas organelas depende fuertemente de su estructura, por lo cual, cualquier alteración en la misma puede afectar la homeostasis celular.

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Relevance of transcriptional condensates in transcription regulation

We explore the molecular mechanisms involved in the regulation of gene expression, which is essential for understanding emergent biological properties such as cellular identity, and relevant processes including development and aging, as well as the development of certain diseases such as cancer.

As model systems, we study pluripotency transcription factors (TFs), which are essential for maintaining embryonic stem cells in an undifferentiated state, and the glucocorticoid receptor, a TF that is activated upon binding glucocorticoids, which are widely used as anti-inflammatory drugs. In particular, we seek to answer the following questions:

• What is the role of transcriptional condensates? These membrane-less compartments concentrate TFs and other transcription-related molecules, and their functions remain poorly understood.
• What mechanisms are involved in the early responses of stem cells to a differentiation signal?
• How do mechanical forces affect the transcriptional program? Cells are constantly exposed to forces from neighbor cells or from the extracellular matrix that are transmitted into the cell nucleus. These forces play an essential role during the early stages of development and guide cell fate decisions in stem cells.
• What is the role of genome architecture in transcriptional regulation? The human genome folds in space to form different types of structures, but the role this three-dimensional organization plays in gene activation is still unclear.

Dynamic organization of the cytoskeleton and its function in the transmission of mechanical signals

We study how the networks that make up the cytoskeleton (microtubules, actin filaments, and intermediate filaments) can generate, transmit, and respond to mechanical signals, both intracellular and those coming from the exterior, thereby influencing cell behavior and fate.

Intracellular transport mediated by molecular motors

We explore the principles that regulate intracellular transport driven by microtubule-dependent molecular motors (kinesin and dynein) and actin filament-dependent motors (myosin), and their relationship with the cellular microenvironment. We seek to characterize how the physical forces exerted by the motors, together with the cytoskeleton, are able to determine the spatial distribution of organelles as well as induce the deformation of larger ones.

In particular, we focus on characterizing mitochondrial dynamics. Mitochondria are organelles essential for cell survival, and their correct positioning in the cytoplasm ensures the proper occurrence of multiple biological processes. Using Xenopus laevis melanophore cells and the U2OS cell line as model systems, we seek to answer the following questions:

• What is the intracellular dynamics of mitochondria like? Mitochondria are organelles that exhibit different morphologies depending on cell type or the metabolic state of the cells. They may have spherical or elongated shapes, or form complex interconnected networks, which affects their dynamics and interaction with the transport system.
• How do the mechanical forces exerted by molecular motors and the cytoskeleton modulate mitochondrial morphology? The proper functioning of these organelles depends strongly on their structure, so any structural alteration may affect cellular homeostasis.

1. Quantification of SnRK1.1 response through analysis of its intracellular distribution. Brugnara C, Diaz MC, Bultri J, Liebsch D, Hita FJ, Lucero DA, Fusari CM, Dengjel J, Levi V, Blanco NE. Plant Cell Rep. 45:26. 2026.
2. OptoLoop – an optogenetic tool to probe the functional role of genome organization.Stortz M, Keikhosravi A, Pegoraro G, Misteli T. J Cell Sci. 139:jcs264574. 2026.
3. Hallmarks of glucocorticoid receptor condensates involvement in transcription regulation. Benítez B, Stortz M, De Rossi MC, Presman DM, Levi V. iScience 28, 112678. 2025.
4. A Simple Method for Generating Light-induced Clusters of Transcription Factors: Effects on the Nuclear Distribution of OCT4 and on its Interactions With Chromatin. Diaz MC, Oses C, Vázquez Lareu A, Roberti SL, Guberman AS, Levi V. J Mol Biol. 437:169118. 2025.
5. Dynamical organization of vimentin intermediate filaments in living cells revealed by MoNaLISA nanoscopy. Smoler M, Pennacchietti F, De Rossi MC, Bruno L, Testa I and Levi V. Bioscience Reports 45: 1–14. 2025.
6. Differential cell architecture and microenvironmental responses of pretumoral and tumoral cellular models exposed to coverslip‑induced hypoxia. Millán M, Parietti F, Lamela F, De Rossi MC, Benítez B, Levi V, Domingues M, Bologna‑Molina R, Arocena M, Hochmann J. Histochemistry and Cell Biology 163:23. 2025.
7. Catching the glucocorticoid receptor in the act: Lessons from fluorescence fluctuation methods. Stortz M, Oses C, Lafuente AL, Presman DM, Levi V. Biochemical and Biophysical Research Communications 748: 151327. 2025.
8. Transcriptional condensates: a blessing or a curse for gene regulation?. Stortz M, Presman DM, Levi V. Commun Biol 187: 3-10. 2024.
9. Deciphering the intracellular forces shaping mitochondrial motion.Fernández Casafuz AB, Brigante AM, De Rossi MC, Monastra AG, Bruno L. Sci Rep 14:23914. 2024.
10. Loss of Direct Vascular Contact to Astrocytes in the Hippocampus as an Initial Event in Alzheimer’s Disease. Evidence from Patients, In Vivo and In Vitro Experimental Models. Pomilio C, Presa J, Oses C, Vinuesa A, Bentivegna M, Gregosa A, Riudavets M, Sevlever G, Galvan V, Levi V, Beauquis J, Saravia F. Molecular Neurobiology doi: 10.1007/s12035-023-03897-5. 2024.
11. From the membrane to the nucleus: mechanical signals and transcription regulation. Oses C, De Rossi MC, Bruno L, Verneri P, Díaz MC, Benitez B, Guberman A, Levi V. Biophysical Reviews. 2023.
12. Mitochondrial cellular organization and shape fluctuations are differentially modulated by cytoskeletal networks.Fernández Casafuz AB, De Rossi MC, Bruno L. Scientific Reports. 13:4065. 2023.
13. Oxidative stress associated with spatial memory impairment and social olfactory deterioration in female mice reveals premature aging aroused by perinatal protein malnutrition. Ferroni NM, Chertoff, MJ, Alberca CD, Berardino BG, Gianatiempo O, Brahamian M, Levi V, Irrutia L, Falasco G, Cánepa ET, Sonzogni SV. Experimental Neurology 368: 114481. 2023.
14. The dynamical organization of the core pluripotency transcription factors responds to differentiation cues in early S-phase. Oses C, Francia MG, Verneri P, Vazquez Echegaray C, Guberman A, Levi V. Front. Cell Dev. Biol., vol 11: doi.org/10.3389/fcell.2023.1125015. 2023.
15. Sumoylation and the oncogenic E17K mutation affect AKT1 subcellular distribution and impact on Nanog-binding dynamics to chromatin in embryonic stem cells. Francia MG, Oses C, Roberti SL, García MR, Cozza LH, Díaz C, Levi V, Guberman AS. Journal of Structural Biology 215(2):107961. 2023.
16. AKT1 induces Nanog promoter in a SUMOylation‑dependent manner in different pluripotent contexts. Francia MG, Verneri P, Oses C, Vazquez Echegaray C, García MR, Toro A, Levi V, Guberman AS. BMC Research Notes 16:309. 2023.
17. SOX2 Modulates the Nuclear Organization and Transcriptional Activity of the Glucocorticoid Receptor. Stortz M, Oses C, Vazquez Echegaray C, Pecci A Guberman A, Presman DM and Levi V. Journal of Molecular Biology 434: 167869, 2022.
18. Seeing the smallest rotary biomotor. Levi V. Nature Reviews Molecular Cell Biology. https://doi.org/10.1038/s41580-022-00454-1. 2022.
19. Nucleus-cytoskeleton communication impacts on OCT4-chromatin interactions in embryonic stem cells. Romero JJ, De Rossi MC, Oses C, Vázquez Echegaray C, Verneri P, Francia M, Guberman A and Levi V. BMC Biology 20:6, 2022.
20. Morphological fluctuations of individual mitochondria in living cells. Fernández Casafuz AB, De Rossi MC, Bruno L. J Phys Condens Matter 34. 2021.
21. Pluripotency transcription factors at the focus: the phase separation paradigm in stem cells. Oses C, Stortz M, Verneri P,  Guberman A y Levi V. Biochemical Society Transactions, 49(6):2871-2878.
22. SUMO conjugation susceptibility of Akt/Protein kinase B affects the expression of the pluripotency transcription factor Nanog in embryonic stem cells. Marcos Francia, Martin Stortz, Camila Vazquez Echegaray, María Victoria Petrone, Ayelen Toro, Camila Oses, Ariel Waisman, Santiago Miriuka, María Soledad Cosentino, Valeria Levi, and Alejandra Guberman. PlosONE, 16(7): e0254447. 2021
23. Extraction-free protocol combining proteinase K and heat inactivation for detection of SARS-CoV-2 by RT-qPCR. Valeria Genoud, Martin Stortz , Ariel Waisman, Bruno G. Berardino, Paula Verneri, Virginia Dansey, Melina Salvatori, Federico Remes Lenicov, Valeria Levi. PLoSONE 16(2):e0247792. 2021
24. Phasing the intranuclear organization of steroid hormone receptors. Stortz M, Presman D, Pecci A, Levi V. Biochemical Journal 478(2):443-461. 2021.
25. The intramolecular self-healing strategy applied to near infrared fluorescent aminotricarbocyanines. Abbas JM, Stortz M, Rodríguez H, Levi V, Wolosiuk A, Spagnuolo C. Dyes and Pigments 186: 109040. 2021.
26. Novel Interplay between p53 and HO-1 in Embryonic Stem Cells. Toro A, Anselmino N, Solari C, Francia M, Oses C, Sanchis P, Bizzotto J, Vazquez Echegaray C, Petrone MV, Levi V, Vazquez E, Guberman A. Cells, 10(1), 35; https://doi.org/10.3390/cells10010035. 2020.
27. Unraveling the Molecular Interactions Involved in Phase Separation of Glucocorticoid Receptor. Stortz M, Pecci A, Presman D, Levi V. BMC Biology 59, 2020.
28. Intracellular motor-driven transport of rod-like smooth organelles along microtubules. Fernández Casafuz AB, De Rossi MC, Bruno L. Phys Rev E 101: 062416. 2020.
29. Apparent stiffness of vimentin intermediate filaments in living cells and its relation with other cytoskeletal polymers. Smoler M, Coceano G, Testa I, Bruno L, Levi V. BBA – Molecular Cell Research 1867(8):118726. 2020.
30. Dynamical reorganization of the pluripotency transcription factors Oct4 and Sox2 during early differentiation of embryonic stem cells. Verneri P, Vazquez Echegaray C, Oses C, Stortz M, Guberman A and Levi V. Sci Rep, 10:5195. (Forma parte del #Top100 entre los artículos más descargados de esta revista durante 2020 en el área de biología celular y molecular)
31. Fluorescence correlation spectroscopy reveals the dynamics of kinesins interacting with organelles during microtubule-dependent transport in cells. MC De Rossi, N González Bardeci, Y Álvarez, E Mocksos, JJ Romero, L Bruno, DE Wetzler,; V Levi. BBA – Molecular Cell Research, 1867:118572. 2020.
32. The glucocorticoid receptor interferes with progesterone receptor-dependent genomic regulation in breast cancer cells. MF Ogara, SA Rodríguez-Seguí, M Marini, AS Nacht, M Stortz, V Levi, DM Presman, GP Vicent, A Pecci. Nucleic Acids Research, 47:10645-10661. 2019.
33. Kat6b modulates Oct4 and Nanog binding to chromatin in embryonic stem cells and is required for efficient neural differentiation. Cosentino M; Oses C; Vazquez Echegaray C; Solari C; Waisman A; Álvarez Y; Petrone MV; Francia MG; Schultz M; Sevlever G; Miriuka S; Levi V; Guberman A. J Mol Biol, 431:1148-1159. 2019.
34. Click–based thiol-ene photografting of COOH groups to SiO₂ nanoparticles: strategies comparison. Jazmín Penelas, Galo J.A.A. Soler-Illia, Levi Valeria, Andrea V. Bordoni, Alejandro Wolosiuk. Colloids and Surfaces A: Physicochemical and Engineering Aspects 562: 61-70. 2019.
35. Imaging transcription factors dynamics with advanced fluorescence microscopy methods. Paula Verneri, Juan José Romero, María Cecilia De Rossi, Yanina Alvarez, Camila Oses, Alejandra Guberman and Valeria Levi. Mechanisms of Development 154:60-63. 2018.
36. Proteasome stress leads to APP axonal transport defects by promoting its amyloidogenic processing in lysosomes. Otero MG, Bessone IF, Hallberg AE, Cromberg LE, De Rossi MC, Saez TM, Levi V, Almenar-Queralt A, Falzone TL. J Cell Sci. 131 jcs214536. 2018.
37. Retraction of rod-like mitochondria during microtubule-dependent transport. María Cecilia De Rossi, Valeria Levi* and Luciana Bruno*. Bioscience reports 38(3). pii: BSR20180208. 2018
38. Mapping the dynamical organization of the cell nucleus through fluorescence correlation spectroscopy. Martin Stortz, Juan Angiolini, Esteban Mocksos, Alejandro Wolosiuk, Adali Pecci, Valeria Levi. Methods: 140-141:10-22. 2018.
39. Mechanical coupling of microtubule-dependent motor teams during peroxisome transport in Drosophila S2 cells. María Cecilia De Rossi, Diana E.Wetzler, Lorena Benseñor, María Emilia De Rossi, Mariela Sued, Daniela Rodríguez, Vladimir Gelfand, Luciana Bruno, Valeria Levi. BBA-General Subjects 1861(12):3178-3189. 2017
40. Diffusion of single dye molecules in hydrated TiO₂ mesoporous films. Juan F. Angiolini, Martín Stortz, Paula Y. Steinberg, Esteban Mocskos, Luciana Bruno, Galo Soler-Illia, Paula C. Angelomé, Alejandro Wolosiuk, and Valeria Levi. Phys Chem Chem Phys 19(39):26540-26544. 2017.
41. Mapping the Dynamics of the Glucocorticoid Receptor within the Nuclear Landscape. Martin Stortz, Diego M. Presman, Luciana Bruno, Paolo Annibale, Maria V. Dansey, Gerardo Burton, Enrico Gratton, Adali Pecci and Valeria Levi, Sci Rep: 6219. 2017
42. Characterization of microtubules buckling in living cell. Carla Pallavicini, Alejandro Monastra, Nicolás González Bardeci, Diana Wetzler , Valeria Levi and Luciana Bruno Eur Biophys J 46:581-594. 2017.
43. Dynamics of intracellular processes in live-cell systems unveiled by fluorescence correlation microscopy. Nicolás González Bardeci, Juan Francisco Angiolini, María Cecilia De Rossi, Luciana Bruno and Valeria Levi. IUBMB Life 69(1):8-15. 2017
44. Heme oxygenase-1 in the forefront of a multi-molecular network that governs cell–cell contacts and filopodia-induced zippering in prostate cancer. Alejandra Paez, Carla Pallavicini, Federico Schuster, Maria Pia Valacco, Jimena Giudice, Emiliano Ortiz, Nicolás Anselmino, Estefania Labanca, Maria Binaghi, Marcelo Salierno, Marcelo Martí, Javier Cotignola, Anna Woloszynska-Read, Luciana Bruno, Valeria Levi, Nora Navone, Elba Vazquez and Geraldine Gueron. Cell Death and Disease 7(12):e2570. 2016
45. Quantitative imaging of mammalian transcriptional dynamics: from single cells to whole embryos. Ziqing W Zhao; Melanie D White; Stephanie Bissiere; Valeria Levi; Nicolas Plachta. BMC Biology 14:115. 2016
46. Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo. Melanie D. White, Juan Francisco Angiolini, Yanina D. Alvarez, Gurpreet Kaur, Ziqing W. Zhao, Esteban Mocskos, Luciana Bruno, Stephanie Bissiere, Valeria Levi*, Nicolas Plachta* (*los dos son autores correspondientes). Cell 165(1):75-87. 2016. Este artículo fue tapa de la revista
47. One photon lithography for high-quality lipid bilayer micro-patterns. Sánchez, M. Florencia; Dodes Traian, Martín; Levi, Valeria*; Carrer, Dolores*. Langmuir 31(43):11943-50. 2015
48. Agonist mobility on supported bilayers affects Fas mediated death response. M. Florencia Sánchez, Valeria Levi, Thomas Weidemann and Dolores C. Carrer. FEBS Letters 589 (23):3527-33. 2015
49. Asymmetries in kinesin-2 and cytoplasmic dynein contributions to melanosome transport. María Cecilia De Rossi, María Emilia De Rossi, Mariela Sued, Daniela Rodríguez, Luciana Bruno, Valeria Levi. FEBS Letters, 589(19 Pt B):2763-8. 2015
50. Exploring the dynamics of cell processes through Monte Carlo simulations of advanced fluorescence microscopy experiments. Juan Angiolini, Nicolas Plachta, Esteban Mocskos, Valeria Levi. Biophysical Journal 108(11):2613-8. 2015. seleccionada por el Editor como una de las 13 “outstanding contributions” contribuciones más importantes en el campo de métodos de fluorescencia durante el año de su publicación http://www.cell.com/biophysj/collections/fluorescence-methods

(Últimos 5 años) / (Last 5 years)

2025. Imaging 4 All grant (Global Bioimaging), Valeria Levi

2022-2026 PICT-2020-00818, Valeria Levi

2020 2026 UBACYT 20020190100101BA, Valeria Levi

2019 2022 PICT-2018-01921 , Valeria Levi

Nos interesa incorporar estudiantes de grado, posgrado y posdocs motivados/as en trabajar interdisciplinariamente en temas que requieren miradas desde la biología, química, física y computación.

Contacto: vlevi12@gmail.com

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We are interested in welcoming motivated undergraduate and graduate students, as well as postdoctoral researchers, who are eager to work in an interdisciplinary environment on topics that require perspectives from biology, chemistry, physics, and computer science.

Contact: vlevi12@gmail.com