Professor Alpha Yap

Professorial Research Fellow - GL

Institute for Molecular Bioscience

Affiliated Professor

School of Biomedical Sciences
Faculty of Medicine
a.yap@imb.uq.edu.au
+61 7 334 62013

Overview

My group studies the role of cadherin cell adhesion molecules in morphogenesis and tumor development. E-cadherin is a key mediator of cell-cell recognition. It participates in tissue patterning and its dysfunction contributes to tumor progression and invasion.

Associate Professor Yap is the group leader for Cadherin cell adhesion molecules, Epithelial morphogenesis & Cell locomotion research at the IMB.

Research Interests

  • Cadherin cell adhesion molecules, Epithelial morphogenesis & Cell locomotion
    We seek to understand the cellular basis of cadherin recognition, and how this controls cell movement and organisation. We are studying the molecular and cellular mechanisms by which cadherin cell adhesion molecules mediate cell-cell recognition. Our current work builds on two recent discoveries made by my lab. Firstly, we found that E-cadherin, the principal cadherin molecule found in epithelial tissues, functions as an adhesion-activated cell signaling receptor. In particular, upon adhesion E-cadherin activates signaling via the small GTPase, Rac, and the lipid kinase PI3-kinase. Finally, an important potential target of this signaling receptor is the Arp2/3 protein complex, a protein machine that nucleates assembly of actin filaments. We were the first to discover that E-cadherin interacts with the Arp2/3 complex to mark sites for actin assembly within cells. We are now exploring the general hypothesis that cadherin-activated signaling controls the subcellular localization and activity of Arp2/3 to modulate cell shape changes and motility in response to productive cell-cell recognition.

Qualifications

  • Doctor of Philosophy, The University of Queensland
  • Fellow Royal Australasian College of Physicians
  • Bachelor of Medicine, Bachelor of Surgery (Hons), The University of Queensland
  • Bachelor of Medical Science, The University of Queensland

Publications

  • Katsuno-Kambe, Hiroko, Parton, Robert G, Yap, Alpha S and Teo, Jessica L (2021). Caveolin-1 influences epithelial collective cell migration via FMNL2 formin. Biology of the Cell, 113 (2), 107-117. doi: 10.1111/boc.202000116

  • Duszyc, Kinga, Gomez, Guillermo A., Lagendijk, Anne K., Yau, Mei-Kwan, Nanavati, Bageshri Naimish, Gliddon, Briony L., Hall, Thomas E., Verma, Suzie, Hogan, Benjamin M., Pitson, Stuart M., Fairlie, David P., Parton, Robert G. and Yap, Alpha S. (2021). Mechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to engage apical extrusion. Current Biology, 31 (6), 1326-1336.e5. doi: 10.1016/j.cub.2021.01.003

  • Gormal, Rachel S., Padmanabhan, Pranesh, Kasula, Ravikiran, Bademosi, Adekunle T., Coakley, Sean, Giacomotto, Jean, Blum, Ailisa, Joensuu, Merja, Wallis, Tristan P., Lo, Harriet P., Budnar, Srikanth, Rae, James, Ferguson, Charles, Bastiani, Michele, Thomas, Walter G., Pardon, Els, Steyaert, Jan, Yap, Alpha S., Goodhill, Geoffrey J., Hilliard, Massimo A., Parton, Robert G. and Meunier, Frédéric A. (2020). Modular transient nanoclustering of activated β2-adrenergic receptors revealed by single-molecule tracking of conformation-specific nanobodies. Proceedings of the National Academy of Sciences of the United States of America, 117 (48), 30476-30487. doi: 10.1073/pnas.2007443117

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Grants

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Supervision

  • Doctor Philosophy

  • Doctor Philosophy

  • Doctor Philosophy

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Available Projects

  • Epithelial tissues are the principal barriers in our body and the source of common diseases, notably cancer and inflammation. The surprising thing is that despite the fact that they are subject to constant bombardment by toxins, infection and transformation, epithelia stay healthy most of the time – and keep us healthy. This is because epithelia possess mechanisms to maintain homeostasis: to detect potential insults and respond appropriately. We believe that a major early-warning system involves changes in mechanical tension upon injury or transformation: these are detected by the neighbouring epithelium, which responds by eliminating the affected cells. These changes in mechanical force are transmitted through cell-cell junctions and detected at those junctions by mechanotransduction. Conversely, events that compromise junctional mechanotransduction can render epithelia vulnerable to disease.

    This project builds on our recent discovery that mechanical tension in an epithelium prevents it from eliminating newly-developed cancers. We aim to elucidate how this tissue hypertension prevents cancer elimination and how it may promote growth of those retained cancer cells.To do this, we combine cell biology with organoid and animal models, collaborating with developmental biologists, cancer biologists, mathematicians, engineers and physicists.

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Publications

Book Chapter

  • Priya, Rashmi and Yap, Alpha S. (2015). Active Tension: The Role of Cadherin Adhesion and Signaling in Generating Junctional Contractility. Cellular Adhesion in Development and Disease. (pp. 65-102) edited by Alpha S. Yap. Maryland Heights, MO United States: Academic Press. doi: 10.1016/bs.ctdb.2014.11.016

  • Acharya, B. R. and Yap, A. S. (2015). Cell-cell adhesion and the cytoskeleton. Encyclopedia of cell biology. (pp. 704-712) edited by Ralph A. Bradshaw and Philip D. Stahl. Kidlington, Oxford, United Kingdom: Elsevier. doi: 10.1016/B978-0-12-394447-4.20068-0

  • Ratheesh, Aparna, Priya, Rashmi and Yap, Alpha S. (2013). Coordinating Rho and Rac: the regulation of Rho GTPase signaling and cadherin junctions. Progress in molecular biology and translational science: the molecular biology of cadherins. (pp. 49-68) edited by Frans Van Roy. London, United Kingdom: Academic Press (Elsevier). doi: 10.1016/B978-0-12-394311-8.00003-0

  • Han, Siew Ping and Yap, Alpha S. (2012). The cytoskeleton and classical cadherin adhesions. Adherens junctions: From molecular mechanisms to tissue development and disease. (pp. 111-135) edited by Tony Harris. Dordrecht, Netherlands: Springer. doi: 10.1007/978-94-007-4186-7_6

Journal Article

Conference Publication

Other Outputs

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Epithelial tissues are the principal barriers in our body and the source of common diseases, notably cancer and inflammation. The surprising thing is that despite the fact that they are subject to constant bombardment by toxins, infection and transformation, epithelia stay healthy most of the time – and keep us healthy. This is because epithelia possess mechanisms to maintain homeostasis: to detect potential insults and respond appropriately. We believe that a major early-warning system involves changes in mechanical tension upon injury or transformation: these are detected by the neighbouring epithelium, which responds by eliminating the affected cells. These changes in mechanical force are transmitted through cell-cell junctions and detected at those junctions by mechanotransduction. Conversely, events that compromise junctional mechanotransduction can render epithelia vulnerable to disease.

    This project builds on our recent discovery that mechanical tension in an epithelium prevents it from eliminating newly-developed cancers. We aim to elucidate how this tissue hypertension prevents cancer elimination and how it may promote growth of those retained cancer cells.To do this, we combine cell biology with organoid and animal models, collaborating with developmental biologists, cancer biologists, mathematicians, engineers and physicists.