Melike Lakadamyali, Ph.D.
415 Curie Blvd
764 Clinical Research Building
Philadelphia, PA 19104
University of Texas, Austin, 2001.
Harvard University, 2006.
Description of Research ExpertiseMy 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 PublicationsOtterstrom Jason, Castells-Garcia Alvaro, Vicario Chiara, Gomez-Garcia Pablo A, Cosma Maria Pia, Lakadamyali Melike: Super-resolution microscopy reveals how histone tail acetylation affects DNA compaction within nucleosomes in vivo. Nucleic acids research Jul 2019.
Cella Zanacchi Francesca, Manzo Carlo, Magrassi Raffaella, Derr Nathan D, Lakadamyali Melike: Quantifying Protein Copy Number in Super Resolution Using an Imaging-Invariant Calibration. Biophysical journal 116(11): 2195-2203, Jun 2019.
Mohan Nitin, Sorokina Elena M, Verdeny Ione Vilanova, Alvarez Angel Sandoval, Lakadamyali Melike: Detyrosinated microtubules spatially constrain lysosomes facilitating lysosome-autophagosome fusion. The Journal of cell biology 218(2): 632-643, Feb 2019.
Cutrale Francesco, Rodriguez Daniel, Hortigüela Verónica, Chiu Chi-Li, Otterstrom Jason, Mieruszynski Stephen, Seriola Anna, Larrañaga Enara, Raya Angel, Lakadamyali Melike, Fraser Scott E, Martinez Elena, Ojosnegros Samuel: Using enhanced number and brightness to measure protein oligomerization dynamics in live cells. Nature protocols 14(2): 616-638, 02 2019.
Lock John G, Jones Matthew C, Askari Janet A, Gong Xiaowei, Oddone Anna, Olofsson Helene, Göransson Sara, Lakadamyali Melike, Humphries Martin J, Strömblad Staffan: Reticular adhesions are a distinct class of cell-matrix adhesions that mediate attachment during mitosis. Nature cell biology 20(11): 1290-1302, Nov 2018.
Porto Vanesa, Borrajo Erea, Buceta David, Carneiro Carmen, Huseyinova Shahana, Domínguez Blanca, Borgman Kyra J E, Lakadamyali Melike, Garcia-Parajo Maria F, Neissa José, García-Caballero Tomás, Barone Giampaolo, Blanco M Carmen, Busto Natalia, García Begoña, Leal José Maria, Blanco José, Rivas José, López-Quintela M Arturo, Domínguez Fernando: Silver Atomic Quantum Clusters of Three Atoms for Cancer Therapy: Targeting Chromatin Compaction to Increase the Therapeutic Index of Chemotherapy. Advanced materials (Deerfield Beach, Fla.) Page: e1801317, Jul 2018.
Ladépêche Laurent, Planagumà Jesús, Thakur Shreyasi, Suárez Irina, Hara Makoto, Borbely Joseph Steven, Sandoval Angel, Laparra-Cuervo Lara, Dalmau Josep, Lakadamyali Melike: NMDA Receptor Autoantibodies in Autoimmune Encephalitis Cause a Subunit-Specific Nanoscale Redistribution of NMDA Receptors. Cell reports 23(13): 3759-3768, Jun 2018.
Spiess Matthias, Hernandez-Varas Pablo, Oddone Anna, Olofsson Helene, Blom Hans, Waithe Dominic, Lock John G, Lakadamyali Melike, Strömblad Staffan: Active and inactive β1 integrins segregate into distinct nanoclusters in focal adhesions. The Journal of cell biology 217(6): 1929-1940, Jun 2018.
Gómez-García Pablo A, Garbacik Erik T, Otterstrom Jason J, Garcia-Parajo Maria F, Lakadamyali Melike: Excitation-multiplexed multicolor superresolution imaging with fm-STORM and fm-DNA-PAINT. Proceedings of the National Academy of Sciences of the United States of America 115(51): 12991-12996, 12 2018.
Neguembor Maria V, Sebastian-Perez Ruben, Aulicino Francesco, Gomez-Garcia Pablo A, Cosma Maria P, Lakadamyali Melike: (Po)STAC (Polycistronic SunTAg modified CRISPR) enables live-cell and fixed-cell super-resolution imaging of multiple genes. Nucleic acids research 46(5): e30, Dec 2017.