Melike Lakadamyali, Ph.D.

faculty photo
Assistant 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

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.

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.

Ojosnegros Samuel, Cutrale Francesco, Rodríguez Daniel, Otterstrom Jason J, Chiu Chi Li, Hortigüela Verónica, Tarantino Carolina, Seriola Anna, Mieruszynski Stephen, Martínez Elena, Lakadamyali Melike, Raya Angel, Fraser Scott E: Eph-ephrin signaling modulated by polymerization and condensation of receptors. Proceedings of the National Academy of Sciences of the United States of America 114(50): 13188-13193, Dec 2017.

Runa Sabiha, Lakadamyali Melike, Kemp Melissa L, Payne Christine K: TiO2 Nanoparticle-Induced Oxidation of the Plasma Membrane: Importance of the Protein Corona. The journal of physical chemistry. B 121(37): 8619-8625, Sep 2017.

Ricci Maria Aurelia, Cosma Maria Pia, Lakadamyali Melike: Super resolution imaging of chromatin in pluripotency, differentiation, and reprogramming. Current opinion in genetics & development 46: 186-193, Aug 2017.

Zanacchi Francesca Cella, Manzo Carlo, Alvarez Angel S, Derr Nathan D, Garcia-Parajo Maria F, Lakadamyali Melike: A DNA origami platform for quantifying protein copy number in super-resolution. Nature methods 14(8): 789-792, Aug 2017.

Kieffer-Kwon Kyong-Rim, Nimura Keisuke, Rao Suhas S P, Xu Jianliang, Jung Seolkyoung, Pekowska Aleksandra, Dose Marei, Stevens Evan, Mathe Ewy, Dong Peng, Huang Su-Chen, Ricci Maria Aurelia, Baranello Laura, Zheng Ying, Ardori Francesco Tomassoni, Resch Wolfgang, Stavreva Diana, Nelson Steevenson, McAndrew Michael, Casellas Adriel, Finn Elizabeth, Gregory Charles, St Hilaire Brian Glenn, Johnson Steven M, Dubois Wendy, Cosma Maria Pia, Batchelor Eric, Levens David, Phair Robert D, Misteli Tom, Tessarollo Lino, Hager Gordon, Lakadamyali Melike, Liu Zhe, Floer Monique, Shroff Hari, Aiden Erez Lieberman, Casellas Rafael: Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation. Molecular cell 67(4): 566-578.e10, Jul 2017.

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Last updated: 10/30/2018
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