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Dr YU, Cheng-Han 游承翰

Dr YU, Cheng-Han 游承翰

  • BSc (NTU, Taiwan); PhD (UC Berkeley)
  • Assistant Professor
L1-49, Laboratory Block, 21 Sassoon Road, Hong Kong
+852 3917 9205
+852 2817 0857
  • Integrin signaling in cell-matrix adhesion
  • Lipid signaling in podosomes and invadopodia
  • Mechanobiology and cancer metastasis
  • Advanced fluorescence microscopy and image analysis
  • Bio-functionalized supported lipid membrane
  • Research Fellow, Mechanobiology Institute, National University of Singapore, Singapore (2010-2014)
  • Postdoctoral Fellow, Howard Hughes Medical Institute, Berkeley, CA, USA (2008-2009)
  • Ph.D., University of California, Berkeley, CA, USA (2002-2007)
  • B.Sc., National Taiwan University, Taipei, Taiwan (1996-2000)
  • Member, Centre for Cancer Research, The University of Hong Kong
  • Member, Strategic Research Theme of Cancer, The University of Hong Kong
  • Member, Strategic Research Theme of Development and Reproduction, The University of Hong Kong.

My research focuses on direct visualization of molecular reorganization and signal transduction by advanced fluorescence microscopy and super-resolution microscopy.  We are currently interested in the kinase and phosphatase interaction at integrin-mediated adhesion, such as podosomes and invadopodia in metastasis cancer cells. Cross-talk between integrin and other membrane kinase plays critical roles in cell migration and invasion. In addition, we will apply super-resolution microscopy to resolve fine structure at invadosome.

(a) Adhesion signaling

Integrin-mediated cell adhesion, a well-known example, involves micron-scale protein assembly and actin cytoskeleton remodeling at the interface of cell and extracellular matrices. However, the mechanism of extracellular matrix organization regulates outside-in integrin activation remains unclear. To address the spatial-temporal regulation of integrin activation, we utilize self-assembling proteolipid bilayer membrane with fluorescent cyclic RGD peptides as adhesion substrates.

This configuration, known as a supported membrane, preserves the important characteristics of cell membrane, i.e. two-dimensional mobility. Fluid supported membrane can also be physically partitioned by pre-fabricated nano-barriers and can passively modulate the spatial organization patterns of ligand-receptor complexes.  Combined with state-of-art fluorescence microscopy, it enables me to study the activation of integrin receptors and dynamical assembly of functional complexes during early adhesion formation (Yu et al, PNAS 2011; Iskratsch, Yu, et al, Dev Cell 2013).

(b) Cancer invadosomes

Adhesion transformation from regular focal adhesion to malignant invadopodia/podosome is the key invasion process in the metastatic cancer development. Our recent report indicated that the formation of different adhesion structures is modulated by mechanical characteristics of matrices. Lack of traction force at activated integrin clusters results in podosome formation in PI3K and FAK/PYK2 dependent manner. The switching between classic focal adhesions to podosomes is remarkable. While metastatic cancer cells also develop similar protrusive machinery, namely invadopodia, PI3K, FAK, and Pyk2 are all pharmaceutical targets to suppress tumor invasions. This groundbreaking finding directly suggests programmable adhesion transformation by matrix-mediated mechano-transduction (Yu et al, Cell reports, 2013).

  • Adhesion disassembly in invadosome
  • Lipid signaling in adhesion transformation
  • Host-pathogen interaction and cancer invasion
  1. Cheng-han Yu*, Nisha Bte Mohd Rafiq, Yuhuan Zhou, Fakun Cao, Anitha Krishnasamy, Kabir Hassan Biswas, Andrea Ravasio, Zhongwen Chen, Yu-Hsiu Wang, Keiko Kawauchi, Gareth E. Jones, and Michael P. Sheetz*. “Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force”. Nature Communications 2015, 6, 8672. *corresponding authors
  2. Shota Yamauchi, Hou Yanyan, Alvin Guo Kunyao, Hiroaki Hirata, Wataru Nakajima, Yip Ai Kia, Cheng-han Yu, Ichiro Harada, Chiam Keng-Hwee, Yasuhiro Sawada, Nobuyuki Tanaka, Keiko Kawauchi. “The mitochondrial protease HtrA2/Omi mediates oncogenic Ras-induced remodeling of the actin cytoskeleton to suppress cell invasion”. Journal of Cell Biology, 2014, 204:1191-1207.
  3. Lars Iversen, Hsiung-Lin Tu, Wan-Chen Lin, Sune M. Christensen, Steven M. Abel, Jeff Iwig, Hung-Jen Wu, Jodi Gureasko, Christopher Rhodes, Rebecca S. Petit, Scott D. Hansen, Peter Thill, Cheng-Han Yu, Dimitrios Stamou, Arup K. Chakraborty, John Kuriyan, and Jay T. Grove. “Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics”. Science 2014, 345, 50-54.
  4. Cheng-han Yu*, Nisha Bte Mohd Rafiq, Anitha Krishnasamy, Gareth E. Jones, Alexander D. Bershadsky, Michael P. Sheetz*. “Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces”. Cell Reports 2013, 5, 1456-1468. *Corresponding authors
  5. Thomas Iskratsch, Cheng-han Yu, Anurag Mathur, Joseph Dwyer, Lale Alpar, James Hone, Elisabeth Ehler and Michael Sheetz. “FHOD1 is needed for directed Forces and Adhesion Maturation during Cell Spreading and Migration”. Developmental Cell 2013, 27, 545-559.
  6. Weiwei Luo, Cheng-han Yu, Jun Allard, Alex Mogilner, Michael P. Sheetz and Alexander Bershadsky. “Organization and dynamics of cytoplasmic actin networks”. Journal of Cell Biology 2013, 202:1057-1073.
  7. Lars Iversen, Hsiung-Lin Tu, Wan-Chen Lin, Sune M. Christensen, Steven M. Abel, Jeff Iwig, Hung-Jen Wu, Jodi Gureasko, Christopher Rhodes, Rebecca S. Petit, Scott D. Hansen, Peter Thill, Cheng-Han Yu, Dimitrios Stamou, Arup K. Chakraborty, John Kuriyan, and Jay T. Grove. “Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics”. Science 2014, 345, 50-54.
  8. Cheng-han Yu, Jaslyn Bee Khuan Law, Mona Suryana, Hong Yee Low, Michael Sheetz. “Early Integrin Binding to RGD Activates Actin Polymerization and Contractile Movement that Stimulates Outward Translocation”. PNAS 2011, 108(51), 20579-20584.
  • RGC ECS Grant #27110615 (2015-2018)
  • MBI research seed grant, National University of Singapore, as collaborator (2010-2013)
  • National Science Council, Taiwan (NSC98-2917-I-564-165), as young investigator (2010-2012)
  • Discussion leader, Gordon Research Seminar: Adhesion Receptor Signaling (2014)
  • Keynote Speaker, Gordon Research Seminar: Signaling by Adhesion Receptors (2012)
  • Conference award, Mechanobiology Workshop, Singapore (2009)