- 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
- Yuhuan Zhou, Zhen Feng, Fakun Cao, Xiaoting Liu, Xiaojie Xia, and Cheng-han Yu*. “Abl-mediated PI3K activation regulates macrophage podosome formation”. Journal of Cell Science (2020) 133, jcs234385. doi:10.1242/jcs.234385. *corresponding author
- Fakun Cao, Yuhuan Zhou, Xiaoting Liu, and Cheng-han Yu*. “Podosome formation promotes plasma membrane invagination and integrin-β3 endocytosis on a viscous RGD-membrane.” Communications Biology 2020, 3(1):117. *corresponding author
- Yage Zhang, Fakun Cao, Yuhuan Zhou, Zhen Feng, Brian Sit, Mira Krendel, and Cheng-han Yu*. “Tail domains of myosin-1e regulate phosphatidylinositol signaling and F-actin polymerization at the ventral layer of podosomes”. Molecular Biology of the Cell 2019, 30(5): 622-635. *corresponding author
- Yangzi Chen, Junshi Li, Fakun Cao, Jason Lam, Clooney CY Cheng, Cheng-han Yu*, and Michael SY Huen*. “Nucleolar residence of the seckel syndrome protein TRAIP is coupled to ribosomal DNA transcription”. Nucleic Acids Research 2018, gky775. *corresponding authors
- Nisha Bte Mohd Rafiq, Zi Zhao Lieu, Tingting Jiang, Cheng-han Yu, Paul Matsudaira, Gareth E. Jones, and Alexander D. Bershadsky. “Podosome assembly is controlled by the GTPase ARF1 and its nucleotide exchange factor ARNO”. Journal of Cell Biology 2017, 216, 181-197.
- 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
- 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.
- 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
- 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.
- 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”. Proceedings of the National Academy of Sciences 2011, 108(51), 20579-20584.
- RGC GRF #17118620 (2021-2023)
- RGC GRF #17122019 (2020-2022)
- RGC GRF #17124218 (2019-2021)
- RGC GRF #17124117 (2018-2020)
- Health and Medical Research Fund #04152266 (HMRF 2016/17)
- 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 Conference: Biointerface Science. Lucca (Barga), Italy (2020; postponed to 2022)
- Organizing committee member and lecturer. The 7th HKU-Pasteur Cell Biology Course. University of Hong Kong (2016)
- Organizing committee member and lecturer. Croucher Summer Course in Advanced Imaging. University of Hong Kong (2015 and 2017)
- 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)