Michael SHEETZ
Founding Director and Collaborator, Mechanobiology Institute, National University of Singapore
Affiliations
Professor, Department of Biochemistry & Molecular Biology, UTMB Health
Le Mai Tan Dat (Daniel)
UROPS Intern, Chan Group
Wang Shida
PhD Student, Class of August 2024, Lim Group
Tan Jue Yu Kelly
PhD Student, Class of August 2024, Chan Group
Shelly Anne Gnapragasan
PhD Student, Class of August 2024, Michelot Group
Mariana Barrera Velazquez
PhD Student, Class of August 2024, Dye Group
Michael Sheetz
Collaborator
Research Areas
Cell migration, cell-cell and cell-substrate interaction
Research Interests
The morphology of cells, organs and whole organisms is determined by the generation of forces on the immediate environment, which is either extracellular matrix or adjacent cells. We are currently engaged in studies to understand the detailed molecular mechanisms involved in a variety of phenomena from cancer metastasis to brain function. Further, we are developing several new tools and protocols for measuring cell forces at the molecular level, which are revealing many new aspects of how cells can both generate and respond to external forces. We have an effort underway to define quantitatively the steps involved in cell adhesion to and spreading on a matrix-coated surface. Using a variety of cell lines that are missing proteins in various motility pathways, we are determining the quantitative changes in the spreading process. This will enable us to generate a detailed model of the process of spreading that will be a model for further studies of how cells differentiate, regenerate tissues or metastasize.
Biography
Hailing from Columbia University, Prof Michael Sheetz has more than 40 years’ experience in the biomedical field. Introduced to Singapore by Prof Hew Choy Leong of the National University of Singapore’s Department of Biological Sciences, Prof Sheetz was sought to lead an RCE project. This resulted in a two-year effort to organise and submit a proposal on Mechanobiology where Prof Sheetz set the theme and direction of the Mechanobiology Institute (MBI). As Founding Director of the MBI, he led the institute for 10 years and built it into a world-leading research centre in the field of mechanobiology.
Education
PhD California Institute of Technology
Recent Publications
- Jain K, Kishan K, Minhaj RF, Kanchanawong P, Sheetz MP, and Changede R. Immobile Integrin Signaling Transit and Relay Nodes Organize Mechanosignaling through Force-Dependent Phosphorylation in Focal Adhesions. ACS Nano 2025;. [PMID: 39760672]
- Lin S, Changede R, Farrugia AJ, Bershadsky AD, Sheetz MP, Prost J, and Rupprecht J. Membrane Tilt Drives Phase Separation of Adhesion Receptors. Phys Rev Lett 2024; 132(18):188402. [PMID: 38759206]
- Jain K, Minhaj RF, Kanchanawong P, Sheetz MP, and Changede R. Nano-clusters of ligand-activated integrins organize immobile, signalling active, nano-clusters of phosphorylated FAK required for mechanosignaling in focal adhesions. bioRxiv 2024;. [PMID: 38464288]
- Jain K, Pandey A, Wang H, Chung T, Nemati A, Kanchanawong P, Sheetz MP, Cai H, and Changede R. TiO2 Nano-Biopatterning Reveals Optimal Ligand Presentation for Cell-Matrix Adhesion Formation. Adv Mater 2024;:e2309284. [PMID: 38340044]
- Jain K, Lim KYE, Sheetz MP, Kanchanawong P, and Changede R. Intrinsic self-organization of integrin nanoclusters within focal adhesions is required for cellular mechanotransduction. bioRxiv 2023;. [PMID: 38045378]
- Oh D, Liu X, Sheetz MP, and Kenney LJ. Small, Dynamic Clusters of Tir-Intimin Seed Actin Polymerization. Small 2023;:e2302580. [PMID: 37649226]
- Qin R, Melamed S, Yang B, Saxena M, Sheetz MP, and Wolfenson H. Tumor Suppressor DAPK1 Catalyzes Adhesion Assembly on Rigid but Anoikis on Soft Matrices. Front Cell Dev Biol 2022; 10:959521. [PMID: 35927990]
- Jain K, Kanchanawong P, Sheetz MP, Zhou X, Cai H, and Changede R. Ligand functionalization of titanium nanopattern enables the analysis of cell-ligand interactions by super-resolution microscopy. Nat Protoc 2022;. [PMID: 35896742]
- Toh PJY, Lai JKH, Hermann A, Destaing O, Sheetz MP, Sudol M, and Saunders TE. Optogenetic control of YAP cellular localisation and function. EMBO Rep 2022;:e54401. [PMID: 35876586]
- Oh D, Chen Z, Biswas KH, Bai F, Ong HT, Sheetz MP, and Groves JT. Competition for shared downstream signaling molecules establishes indirect negative feedback between EGFR and EphA2. Biophys J 2022;. [PMID: 35430415]
Lab Members
How does integrin clustering affect integrin signalling?
How does integrin clustering affect integrin signaling? Localization of Integrin The concentration of β subunits is generally high while that of α subunit is the factor limiting the amount of heterodimers that localize on [...]
How is integrin activated?
How is integrin activated? Integrin activation is an important mechanism through which cells regulate integrin function by manipulating the ligand affinity of integrins spatially and temporally. Structural and functional studies suggest that integrins can [...]
What ligands bind to integrin?
What ligands bind to integrin? Integrin-Ligand specificity Humans have at least 18 α subtypes and 8 β subtypes which together generate 24 known binding pairs for the integrins heterodimer (reviewed in [1][2]). The α [...]
What is integrin extension?
What is integrin extension? Integrin extension Upon alteration in the transmembrane and their proximal domains, the bent headpiece extends in less than 1 second [1] with intermediate affinity for ligands. Two models- “switchblade” and [...]
What are guidance cues?
What are guidance cues? During neural development, highly motile structures on the developing neurites, called growth cones, are guided by signals from the extracellular environment. Guidance cues come in many different forms, from diffusible [...]
How do neurotrophins, collapsin, and ephrins, serve as guidance cues?
How do neurotrophins, collapsin, and ephrins, serve as guidance cues? Neurotrophins Stimulating filopodia formation A secreted guidance cue which stimulates filopodia formation in growth cones. Two examples of secreted neurotrophins, brain-derived neurotrophic factor (BDNF) [...]
What is the Hippo-YAP/TAZ tumor-suppressor pathway?
What is the Hippo-YAP/TAZ tumor-suppressor pathway? Mechanical cues control Hippo-YAP/TAZ tumor-suppressor pathway The Hippo signaling pathway is a complex network of proteins that controls organ size via regulation of cellular proliferation, survival and differentiation. [...]
What is the Canonical Wnt Receptor Signaling Pathway?
What is the Canonical Wnt Receptor Signaling Pathway? The canonical Wnt receptor signaling pathway is a series of molecular events that are initiated by the binding of Wnt proteins to the frizzled family of [...]
How is SRF signaling activated?
How is SRF signaling activated? Myocardin, MAL (or MRTF-A) and MRTF-B are the best-studied examples of MRTFs. In the cytoplasm, MRTFs exist in a stable complex with monomeric G-actin via RPEL domains, which exist [...]
What is the NF-κB pathway?
What is the NF-κB pathway? NF-κB (nuclear factor kappa light chain enhancer of activated B cells) is a family of highly conserved transcription factors that regulate many important cellular behaviours, in particular, inflammatory responses, [...]
Which biochemical pathways are regulated by mechanical signals?
Which biochemical pathways are regulated by mechanical signals? Biochemical Mechanotransduction Cells are capable of relaying mechanical stimuli from their physical environment all the way down to the nucleus through electrochemical, biochemical or mechanical pathways. [...]
What is Serum Response Factor?
What is Serum Response Factor? Serum response factor (SRF) is a transcription factor that plays a key role in the transduction of mechanical signals from cytoplasmic actin and the extracellular environment, to the cell [...]
