Faculty

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
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

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.

Lerner J, Gómez-García PA, McCarthy RL, Liu Z, Lakadamyali M, Zaret KS.: Two-parameter single-molecule analysis for measurement of chromatin mobility. STAR Protoc 1: 100223, Dec 2020.

Lerner J, Gomez-Garcia PA, McCarthy RL, Liu Z, Lakadamyali M, Zaret KS.: Two-Parameter Mobility Assessments Discriminate Diverse Regulatory Factor Behaviors in Chromatin. Mol Cell 79: 677-688, Aug 2020.

Heo SJ, Song KH, Thakur S, Miller LM, Cao X, Peredo AP, Seiber BN, Qu F, Driscoll TP, Shenoy VB, Lakadamyali M, Burdick JA, Mauck RL.: Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues. Sci Adv 6: eaax5083, Jun 2020.

Lakadamyali M, Cosma MP.: Visualizing the genome in high resolution challenges our textbook understanding. Nat Methods 17: 371-379, Apr 2020.

Shreyasi Thakur, Peter K. Relich, Elena M. Sorokina, Melina T. Gyparaki, Melike Lakadamyali: ORP1L regulates dynein clustering on endolysosmal membranes in response to cholesterol levels. BiorXiv Preprint (https://doi.org/10.1101/2020.08.28.273037) 2020.

M. T. Gyparaki, A. Arab, E. M. Sorokina, A. N. Santiago-Ruiz, C. H. Bohrer, J. Xiao, M. Lakadamyali : Tau forms oligomeric complexes on microtubules that are distinct from pathological oligomers in disease. BiorXiv preprint (https://doi.org/10.1101/2020.07.07.192146) 2020.

Christopher H. Bohrer, Xinxing Yang, Xiaoli Weng, Brian Tenner, Shreyasi Thakur, Ryan McQuillen, Brian Ross, Matthew Wooten, Xin Chen, Melike Lakadamyali, Jin Zhang, Elijah Roberts, Jie Xiao: A Pairwise Distance Distribution Correction (DDC) algorithm to eliminate blinking-caused artifacts in super-resolution microscopy. BiorXiv preprint (https://doi.org/10.1101/768051) 2020.

Portillo-Ledesma S, Tsao LH, Wagley M, Lakadamyali M, Cosma MP, Schlick T.: Nucleosome Clutches are Regulated by Chromatin Internal Parameters. J Mol Biol Mol Biol, 2020.

Erin M. Masucci, Peter K. Relich, E. Michael Ostap, Erika L. F. Holzbaur, Melike Lakadamyali: Cega: A Single Particle Segmentation Algorithm to Identify Moving Particles in a Noisy System. BiorXiv preprint (https://doi.org/10.1101/2020.12.24.424334) 2020.

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Last updated: 01/18/2021
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