Liliana Attisano

MY RESEARCH OVERVIEW (GO TO SCIENTIFIC OVERVIEW)

Understanding how disruptions in cell communication cause human disease

When cells miscommunicate, it’s not unlike a game of Broken Telephone: messages get garbled and instructions are misunderstood. The consequence for humans, though, is no game.  All cells have the ability to receive outside messages and to communicate with neighboring cells.

Through a series of molecular events, cells can translate this information and modify their behaviour to ensure that they function properly in their environment. Many complex diseases, such as cancer, are the result of disruptions in this information transfer referred to as cell signaling and cell-cell communication. In my laboratory, I am studying three signalling pathways: Wnt, TGFbeta (Transforming Growth Factor-beta) and Hippo pathways.  Although molecularly distinct, these core pathways interact extensively and this crosstalk plays a key role in ensuring normal cell function under varying conditions. Failure in any individual pathway, or in the way the pathways crosstalk, can lead to serious health issues including developmental disorders, neurodegenerative conditions and cancer.  My overall objective is to uncover the fundamental biology behind cell signalling and communication and to apply advanced, multidimensional screening approaches to identify novel protein targets and candidate drugs.  The goal is to translate our findings so that they can be further developed as potential agents to bring clarity back to distorted communication in diseased cells.

SCIENTIFIC RESEARCH OVERVIEW

Contextual Regulation of Signalling Pathways in Human Disease

My laboratory focuses on understanding how intracellular signalling cascades receive and then transmit extracellular signals and thereby modulate complex biological responses. Current areas of particular interest are the TGFbeta, Wnt and Hippo signalling pathways, whose disruption is associated with numerous human cancers.  My lab also studies pathways that regulate neuronal morphology, including the formation of axons and dendrites in primary neurons. We use mammalian cell model systems, biochemical and cell biological methods and mouse model systems to examine how pathway disruption alters cellular and developmental processes. In addition, we use high-throughput robotics-based methods to examine the dynamics of protein-protein interactions, and to screen for alterations in signalling output using siRNA and small-molecule chemical libraries.

SELECT PUBLICATIONS

• Arhgef7 promotes activation of the Hippo pathway core kinase Lats. Heidary Arash E, Song KM, Song S, Shiban A, Attisano L. EMBO J. 2014 Dec 17;33(24):2997-3011.
• The Hippo pathway regulates Wnt/beta-Catenin/signaling. Varelas, X., Miller, B., Sopko, R., Song, S., Gregorieff, A., Fellouse, F.A., Sakuma, R., Pawson, T., Hunziker, W., McNeill, H., Wrana, J., and Attisano, L. Developmental Cell. 2010 Apr 20;18(4):579-91.
• Wnt inhibitor screen reveals iron dependence of β-catenin signaling in cancers. Song S, Christova T, Perusini S, Alizadeh S, Bao RY, Miller BW, Hurren R, Jitkova Y, Gronda M, Isaac M, Joseph B, Subramaniam R, Aman A, Chau A, Hogge DE, Weir SJ, Kasper J, Schimmer AD, Al-awar R, Wrana JL, Attisano L. Cancer Res. 2011 Dec 15;71(24):7628-39.