Associate Professor, Yong Loo Lin School of Medicine, Department of Physiology, NUS, Institute for Molecular and Cell Biology (IMCB, AStar)
Investigations into physiological and molecular mechanisms of the Golabi-Ito-Hall syndrome, which phenocopies severe autism, using transgenic animal models of the syndrome
Investigations into the role of tight junctions proteins such as ZO2 and ZO1 in the regulation of the Hippo-YAP tumor suppressor pathway using cell and animal models
Investigations of new signaling modalities that inhibit YAP oncogene and could be translated into cancer drug discovery
Investigations of a cross talk between WW domain-containing proteins that regulate muscle homeostasis and the Hippo-YAP pathway that controls differentiation and stem cell biology
Investigations into the dominant role of Hippo-YAP tumor suppressor pathway in liver regeneration
Among Prof Sudol’s most significant achievements to date are the identification of a modular protein domain, known as the WW domain, and the characterization of its cognate ligands. In 2004, together with a research team at AxCell-Cytogen company, Marius Sudol reported the first comprehensive protein interaction map for a human modular domain. Today, the WW domain is known to mediate critical signals in tumor suppressor networks, including the Hippo signaling pathway. More importantly, syndromes such as the Golabi-Ito-Hall syndrome of intellectual disability and Liddle syndrome of hypertension are caused by loss-of-function point mutations in the WW domain or its cognate ligands.
The research conducted in Marius Sudol’s laboratory and those of his collaborators over the past two decades has directly contributed to a systems biology level understanding of signaling networks from the perspective of modular protein domains. As a co-founder and co-leader of the Protein Modules Consortium, he advocates systems biology approaches and synthetic biology strategies in designing therapeutic interventions based on the knowledge of the structure and function of protein modules.
Over the course of his scientific career spanning more than three decades, Marius Sudol has authored 130 publications, including original research articles and invited reviews in refereed journals as well as numerous book chapters. His current work focuses on the role of WW domain-containing proteins in the Hippo tumor suppressor network and Golabi-Ito-Hall syndrome of intellectual disability.
The Y65C Missense Mutation in the WW Domain of the Golabi-Ito-Hall Syndrome Protein PQBP1 Affects Its Binding Activity and Deregulates Pre-mRNA Splicing. Tapia, VE, Nicolaescu E, McDonald CB, Musi V, Oka T, Inayoshi Y, Satteson AC, Mazack V, Humbert J, Gaffney JC, Beullens M, Schwartz CE, Landgraf C, Volkmer R, Pastore A, Farooq A, Bollen M, and Sudol M. J. Biol. Chem. 2010 June 18,285(25):19391-19401.
Functional Complex Between YAP2 and ZO-2 is PDZ Domain Dependent, Regulates YAP2 Nuclear Localization and Signaling. Oka T, Remue E, Meerschaert K, Vanloo B, Boucherie C, Gfeller D, Bader GD, Sidhu S, Vandekerckhove J, Gettemans J, Sudol M. Biochemical J. 2010 Dec 15,432(3):461-72. (This article was selected in 2011 by FACULTY BIOLOGY 1000).
Identification, Basic Characterization and Evolutionary Analysis of Differentially Spliced mRNA Isoforms of Human YAP1 Gene. Gaffney CJ, Oka T, Mazack V, Hilman D, Gat U, Muramatsu T, Inazawa J, Golden A, Carey DJ, Farooq A, Tromp G, Sudol M. Gene. 2012 Nov 10,509(2): 215-222.
WW Domains in the Heart of Smad Signaling. Sudol M. Structure. 2012 Oct 10,20(10):1619-1620.
Opposing Roles of Angiomotin Like 1 and Zona Occludens-2 on Pro-apoptotic Function of YAP. Oka T, Schmitt AP, and Sudol M. Oncogene. 2012 Jan 5,31(1):128-134.