Melike Lakadamyali

Associate Professor

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215-746-5150
melikel@pennmedicine.upenn.edu

764 Clinical Research Building

415 Curie Boulevard

Philadelphia, PA 19104

Research Description

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 to 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.

Studying the spatiotemporal organization and regulation of these macromolecular complexes necessitates non-invasive tools that can visualize them with high spatial and high temporal resolution. Single molecule imaging and in recent years the emergence of super-resolution microscopy have opened new doors to visualize the dynamic assembly and disassembly of macromolecular complexes in living cells. 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, Cella-Zanacchi et al Nature Methods, 2017, Gomez-Garcia et al, PNAS, 2018). These methods have enabled us to gain novel insights into the transport of vesicles along their cytoskeletal tracks (Balint et al, PNAS, 2013, Verdeny et al, JCS, 2017, Mohan et al, JCB, 2019), the spatial organization of nucleosomes along the chromatin fiber (Ricci et al, Cell, Otterstrom et al, NAR, 2019, Gomez-Garcia et al, Cell Reports 2020) and the dynamics of chromatin-transcription factor interactions (Lerner et al, Molecular Cell 2020, Gomez-Garcia et al, Cell Reports, 2020). 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, Cella-Zanacchi et al, Nature Methods, 2017, Cella-Zanacchi et al, Biophysical Journal, 2019).

Diversity & Inclusion Initiatives

  • 2020- Co-director, Physiology Department Committee on Diversity and Inclusion
  • 2017 – 2019 Philadelphia SPARK Outreach Program
Degrees & Education

BS University of Texas at Austin, 2001

PhD Harvard University, 2006

Honors & Awards

2016 Technical University of Munich-Institute for Advanced Study Hans Fisher Junior Fellow

2016 Finalist for La Vanguardia Newspaper, best research in Spain award

2014 Ramon y Cajal Fellowship, Spanish Ministry of Education

2013 EMBO Young Investigator Award

Other Perelman School of Medicine Affiliations

Associate Professor of Cell and Developmental Biology

Biochemistry and Molecular Biophysics Graduate Group

Cell and Molecular Biology Graduate Group

Professional Affiliations

Biophysical Society

American Society for Cell Biology

2020-2021 Scientific Advisory Board, Bruker/Vutara Super-resolution Fluorescence Microscopy, USA

2020- Scientific Advisory Board, BioQuant, Heidelberg, Germany

Recent Publications
August 8, 2020
ORP1L regulates dynein clustering on endolysosomal membranes in response to cholesterol levels
Melike Lakadamyali, Ph.D.
S. Thankur, E.M. Sorokina, P.K. Relich, M. Lakadamyali - DOI: 10.1101/2020.08.28.273037
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July 7, 2020
Tau forms oligomeric complexes on microtubules that are distinct from pathological oligomer
Melike Lakadamyali, Ph.D.
M.T. Gyparaki, A. Arab, E.M. Sorokina, A.N. Santiago-Ruiz, C.H. Bohrer, J. Xiao, M. Lakadamyali - DOI: 10.1101/2020.07.07.192146
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April 19, 2021
Cega: a single particle segmentation algorithm to identify moving particles in a noisy system
Melike Lakadamyali, Ph.D.
Masucci EM, Relich PK, Ostap EM, Holzbaur ELF, Lakadamyali M. - DOI: 10.1091/mbc.E20-11-0744
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