Faculty

Melike Lakadamyali, Ph.D.

faculty photo
Associate Professor of Physiology
Department: Physiology

Contact information
University of Pennsylvania, Perelman School of Medicine, Department of Physiology
415 Curie Blvd
764 Clinical Research Building
Philadelphia, PA 19104
Office: 2157465150
Fax: 2157465150
Lab: 2157465150
Education:
BSc (Physics)
University of Texas, Austin, 2001.
PhD (Physics)
Harvard University, 2006.
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Description of Research Expertise

My main interest is to study biology at the level of its macromolecular machines and to gain a quantitative biophysical understanding of how these machines drive important cell biological processes. Since new tools enable new biology, I also develop advanced microscopy methods that aim to overcome the limitations of current methods and help us visualize the macromolecular machineries of the cell in action with high spatiotemporal resolution. Specifically, I am interested in the molecular machinery involved in two fundamental biological processes: transport machinery that drives intracellular trafficking of vesicles and transcriptional machinery that drives gene expression. At the heart of and common to both biological problems is the interaction of multiple proteins with each other and with other proteins to form functional macromolecular nanoscopic complexes. The spatial and temporal organization of these interactions is tightly regulated and the failure to form these macromolecular complexes in the right place and at the right time can have catastrophic consequences. Indeed, protein copy number, protein clustering and protein mobility are all crucial parameters in intracellular transport and transcription; and failure to properly regulate them can lead to the difference between healthy function and disease.
Over the recent years, my group has been pioneering major developments in the field of super-resolution microscopy (Balint et al, PNAS 2013, Durisic et al Nature Methods 2014, Tam et al PLoS One 2014 (a), Tam et al PLoS One 2014 (b)). These methods have enabled us to gain novel insights into the transport of vesicles along their cytoskeletal tracks (Balint et al, PNAS, 2013) and the spatial organization of nucleosomes along the chromatin fiber (Ricci et al, Cell). Importantly, we have taken a highly quantitative biophysical approach in studying these biological processes, going beyond qualitative descriptions towards precise quantitative models. For example, we have made important strides in quantifying the stoichiometry of macromolecular assemblies such as nucleosomes at nanoscale resolution (Durisic et al, J. Neuroscience 2012, Durisic et al Nature Methods, 2014, Ricci et al Cell, 2015).

Selected Publications

Maria Victoria Neguembor, Laura Martin, Álvaro Castells-García, Pablo Aurelio Gómez-García, Chiara Vicario, Davide Carnevali, Jumana AlHaj Abed, Alba Granados, Ruben Sebastian-Perez, Francesco Sottile, Jérôme Solon, Chao-ting Wu, Melike Lakadamyali* and Maria Pia Cosma* (*equal contribution): Transcription-mediated supercoiling regulates genome folding and loop formation. Molecular Cell 81(15): 3065-3081, Aug 2021.

Piechocka IK, Keary S, Sosa-Costa A, Lau L, Mohan N, Stanisavljevic J, Borgman KJE, Lakadamyali M, Manzo C, Garcia-Parajo MF.: Shear forces induce ICAM-1 nanoclustering on endothelial cells that impact on T-cell migration. Biophys J 120: 2644-2656, Jun 2021.

Gyparaki MT, Arab A, Sorokina EM, Santiago-Ruiz AN, Bohrer CH, Xiao J, Lakadamyali M.: Tau forms oligomeric complexes on microtubules that are distinct from tau aggregates. Proc Natl Acad Sci U S A 118: e2021461118, May 2021.

Masucci EM, Relich PK, Ostap EM, Holzbaur ELF, Lakadamyali M.: Cega: a single particle segmentation algorithm to identify moving particles in a noisy system. Mol Biol Cell 32: 931-941, Apr 2021.

Luan J, Xiang G, Gómez-García PA, Tome JM, Zhang Z, Vermunt MW, Zhang H, Huang A, Keller CA, Giardine BM, Zhang Y, Lan Y, Lis JT, Lakadamyali M, Hardison RC, Blobel GA.: Distinct properties and functions of CTCF revealed by a rapidly inducible degron system. Cell Rep 34: 108783, Feb 2021.

Gómez-García PA, Portillo-Ledesma S, Neguembor MV, Pesaresi M, Oweis W, Rohrlich T, Wieser S, Meshorer E, Schlick T, Cosma MP, Lakadamyali M.: Mesoscale Modeling and Single-Nucleosome Tracking Reveal Remodeling of Clutch Folding and Dynamics in Stem Cell Differentiation. Cell Rep 34: 108614, Jan 2021.

Su-Jin Heo, Shreyasi Thakur, Xingyu Chen, Claudia Loebel, Boao Xia, Rowena McBeath, Jason A. Burdick, Vivek B. Shenoy, Robert L. Mauck, Melike Lakadamyali : Chemo-Mechanical Cues Modulate Nano-Scale Chromatin Organization in Healthy and Diseased Connective Tissue Cells. BioRxiv preprint (https://doi.org/10.1101/2021.04.27.441596) 2021.

Mickael Lelek, Melina Gyparaki, Gerti Beliu, Florian Schueder, Juliette Griffié, Suliana Manley, Ralf Jungmann, Markus Sauer, Melike Lakadamyali, and Christophe Zimmer : Single-molecule localization microscopy. Nature Reviews Methods Primers 1(39), 2021.

Bohrer CH, Yang X, Thakur S, Weng X, Tenner B, McQuillen R, Ross B, Wooten M, Chen X, Zhang J, Roberts E, Lakadamyali M, Xiao J.: A pairwise distance distribution correction (DDC) algorithm to eliminate blinking-caused artifacts in SMLM. Nat Methods 2021.

Erin M. Masucci, Peter K. Relich, Melike Lakadamyali, E. Michael Ostap, and Erika L. F. Holzbaur : Kinesin-4 Motor Teams Effectively Navigate Dendritic Microtubule Arrays Through Track Switching and Regulation of Microtubule Dynamics. BioRxiv preprint (https://doi.org/10.1101/2021.02.28.433181) 2021.

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Last updated: 08/16/2021
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