Melike Lakadamyali, Ph.D.

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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
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

Hugelier S, Colosi PL, Lakadamyali M.: Quantitative Single-Molecule Localization Microscopy. Annu Rev Biophys 52: 139-160, May 2023.

Su-Jin Heo, Shreyasi Thakur, Xingyu Chen, Claudia Loebel, Boao Xia, Rowena McBeath, Jason A. Burdick, Vivek B. Shenoy, Robert L. Mauck & Melike Lakadamyali: Aberrant chromatin reorganization in cells from diseased fibrous connective tissue in response to altered chemomechanical cues. Nature Biomedical Engineering 7(2): 177-191, Feb 2023 Notes: https://doi.org/10.1038/s41551-022-00910-5.

Siewert Hugelier, Hannah Kim, Melina Theoni Gyparaki, Charles Bond, Qing Tang, Adriana Naomi Santiago-Ruiz, Sílvia Porta, Melike Lakadamyali : ECLiPSE: A Versatile Classification Technique for Structural and Morphological Analysis of Super-Resolution Microscopy Data. BioRxiv, https://doi.org/10.1101/2023.05.10.540077 (under revision in Nature Methods) 2023 Notes: under revision in Nature Methods.

Coscia SM, Thompson CP, Tang Q, Baltrusaitis EE, Rhodenhiser JA, Quintero- Carmona OA, Ostap EM, Lakadamyali M, Holzbaur ELF: Myo19 tethers mitochondria to endoplasmic reticulum-associated actin to promote mitochondrial fission. Journal of Cell Science 136(5:jcs.260612), 2023.

Qing Tang, Sebastian Sensale, Charles Bond, Jiazheng Xing, Andy Qiao, Siewert Hugelier, Arian Arab, Gaurav Arya, Melike Lakadamyali: Interplay between stochastic enzyme activity and microtubule stability drives detyrosination enrichment on microtubule subsets. Current Biology 2023 Notes: DOI: 10.1016/j.cub.2023.10.068.

Masucci EM, Relich PK, Lakadamyali M, Ostap EM, Holzbaur ELF.: Microtubule dynamics influence the retrograde biased motility of kinesin-4 motor teams in neuronal dendrites. Mol Biol Cell 33(6): ar52, May 2022.

Melike Lakadamyali: Single nucleosome tracking to study chromatin plasticity. Current Opinion in Cell Biology 74: 23-28, February 2022.

Charles Bond, Adriana N. Santiago-Ruiz, Qing Tang, Melike Lakadamyali: Technological advances in super-resolution microscopy to study cellular processes. Molecular Cell 82(2): 315-332, Jan 2022.

Castells-Garcia A, Ed-Daoui I, González-Almela E, Vicario C, Ottestrom J, Lakadamyali M, Neguembor MV, Cosma MP.: Super resolution microscopy reveals how elongating RNA polymerase II and nascent RNA interact with nucleosome clutches. Nucleic Acids Res 50: 175-190, Jan 2022.

Qing Tang, Sebastian Sensale, Charles Bond, Andy Qiao, Siewert Hugelier, Arian Arab, Gaurav Arya, Melike Lakadamyali: Detyrosination enrichment on microtubule subsets is established by the interplay between a stochastically-acting enzyme and microtubule stability. BioRxiv, https://doi.org/10.1101/2022.09.29.510213 (accepted for publication in current Biology) 2022.

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Last updated: 12/04/2023
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