Pakorn Tony KANCHANAWONG
Assistant Professor, Mechanobiology Institute, National University of Singapore
+65 6601 8991 ext 18991
National University of Singapore
5A Engineering Drive 1
Kanchanawong Lab @ NUS
Molecular Mechanics of Mechanotransduction Group
Assistant Professor, Department of Biomedical Engineering, National University of Singapore
Actin remodeling drives bile regurgitation during obstructive cholestasis
Using superresolution imagining to map adherens junction machinery
Reverse engineering molecular machines
Pakorn Tony Kanchanawong
Nanoscale Structure-Function Relationship, Super-resolution Microscopy, Cell-Matrix Interactions, Cell-Cell Interactions, Cellular Biophysics, Mechanobiology of Cell Adhesions and Cell Cortex, Computer Vision, Machine Learning, Bioimaging Technology, Bioimage Informatics.
Cells built complex nanoscale ‘machines’ from basic biomolecular building blocks to perform vital biological functions. These cellular ‘machines’ are at the heart of key processes in mechanobiology, such as cell migration, cell adhesion, and mechanotransduction. Our overarching research goal is to gain a comprehensive insight into the nanoscale structure-function relationship that governs the assembly, organization, dynamics, and functions of these cellular machines. Our approach is highly interdisciplinary, combining advanced imaging technologies with rigorous molecular and cell biology methods.
We have pioneered the use of superresolution microscopy to elucidate nanoscale architecture of cellular structures (Kanchanawong et al., Nature, 2010), and have long-standing involvement in the development of ultra-high resolution 3D imaging techniques, iPALM (Shtengel et al., PNAS 2009). Our focus is in advancing the capability of super-resolution microscopy, using several platforms including our own iPALM system and surface-generated structured illumination techniques.
Super-resolution and advanced microscopy techniques generate beautiful, complex, and exquisitely detailed images of cells in large quantity. These images contain vast amount of information but it is still very challenging to quantitatively, rigorously, and comprehensively analyse such datasets. To fully tap the potential of these 21st century imaging techniques, this analysis bottleneck must be tackled. We have several ongoing projects where we seek to leverage computer vision and machine learning approaches to unlock information contained in super-resolution microscopy images (for example: Zhang et al., MBoC 2017).
Focal adhesions are major cell adhesion structures that mediate cell-extracellular matrix (ECM) adhesions. Focal adhesions play essential roles in mechanotransduction, rigidity sensing, and cell migration. Our focus is in understanding the molecular architecture of focal adhesions (Kanchanawong et al., Nature, 2010) and how they are animated during cellular functions. Our recent work established the roles of the protein Talin as the determinant of focal adhesions architecture (Liu et al., PNAS 2015). Ongoing projects seek to combine nanoscale imaging with molecular engineering approaches to understand the operational principles that control focal adhesions structure and functions.
In tissues, coherent organization of cells depends on cadherin-mediated cell-cell junctions. We have recently elucidated for the nanoscale architecture of cadherin-based cell adhesions, using superresolution microscopy (Bertocchi et al., Nature Cell Biology, 2017; Wu et al., Developmental Cell, 2015). In our ongoing projects we seek to understand comprehensively the transformation and linkages between nanoscale structures and functions during the formation and maturation of epithelial tissues
PhD (Biophysics) Stanford University
Tony Kanchanawong received his Bachelor’s degree (A.B. summa cum laude, 2001) from Cornell University where he double-majored in Chemistry and Biological Sciences. At Cornell, he also studied the Molecular Dynamics of cellulase enzymes in the laboratory of Prof. John W. Brady Jr. Going west to Stanford University, he worked on Non-Classical Stark spectroscopy of photosynthetic reaction centers and GFPs with Prof. Steven G. Boxer, supported by the HHMI Predoctoral Fellowship. In 2007, he received his doctorate in Biophysics and became a postdoctoral fellow in the laboratory of Dr. Clare Waterman at NIH, where he closely collaborated with Dr. Harald Hess at HHMI Janelia Research Campus in the development and application of iPALM 3-D superresolution microscopy. In 2011, Tony started his research group at MBI and NUS Department of Biomedical Engineering, as one of the NRF fellowship recipients.
- Zhang Z, Xia S, and Kanchanawong P. An integrated enhancement and reconstruction strategy for the quantitative extraction of actin stress fibers from fluorescence micrographs. BMC Bioinformatics 2017; 18(1):268. [PMID: 28532442]
- Gupta K, Li Q, Fan JJ, Fong ELS, Song Z, Mo S, Tang H, Ng IC, Ng CW, Pawijit P, Zhuo S, Dong C, Low BC, Wee A, Dan YY, Kanchanawong P, So P, Viasnoff V, and Yu H. Actomyosin Contractility Drives Bile Regurgitation as an Early Response During Obstructive Cholestasis. J. Hepatol. 2017;. [PMID: 28189756]
- Bertocchi C, Wang Y, Ravasio A, Hara Y, Wu Y, Sailov T, Baird MA, Davidson MW, Zaidel-Bar R, Toyama Y, Ladoux B, Mege R, and Kanchanawong P. Nanoscale architecture of cadherin-based cell adhesions. Nat. Cell Biol. 2016;. [PMID: 27992406]
- Wang Y, and Kanchanawong P. Three-dimensional Super Resolution Microscopy of F-actin Filaments by Interferometric PhotoActivated Localization Microscopy (iPALM). J Vis Exp 2016;(118). [PMID: 27929472]
- Zhang Z, Nishimura Y, and Kanchanawong P. Extracting Microtubule Networks from Superresolution Single-Molecule Localization Microscopy Data. Mol. Biol. Cell 2016;. [PMID: 27852898]
- Liu J, Wang Y, Goh WI, Goh H, Baird MA, Ruehland S, Teo S, Bate N, Critchley DR, Davidson MW, and Kanchanawong P. Talin determines the nanoscale architecture of focal adhesions. Proc. Natl. Acad. Sci. U.S.A. 2015; 112(35):E4864-73. [PMID: 26283369]
- Wu Y, Kanchanawong P, and Zaidel-Bar R. Actin-delimited adhesion-independent clustering of E-cadherin forms the nanoscale building blocks of adherens junctions. Dev. Cell 2015; 32(2):139-54. [PMID: 25600236]
- Shtengel G, Wang Y, Zhang Z, Goh WI, Hess HF, and Kanchanawong P. Imaging cellular ultrastructure by PALM, iPALM, and correlative iPALM-EM. Methods Cell Biol. 2014; 123:273-94. [PMID: 24974033]
- Nomachi A, Yoshinaga M, Liu J, Kanchanawong P, Tohyama K, Thumkeo D, Watanabe T, Narumiya S, and Hirata T. Moesin controls clathrin-mediated S1PR1 internalization in T cells. PLoS ONE 2013; 8(12):e82590. [PMID: 24358210]
- Kanchanawong P, and Waterman CM. Localization-based super-resolution imaging of cellular structures. Methods Mol. Biol. 2013; 1046:59-84. [PMID: 23868582]