Stuart Maudsley Lab

Research focus

​Our laboratory is interested in understanding how complex and multifactorial neurodegenerative diseases are generated through the interaction of networks of genes and proteins, and subsequently how to develop tractable receptor-based therapeutic strategies that exert beneficial effects across these pathological networks.

While considerable insight into the genomic basis of neurodegenerative disorders, such as Alzheimer’s and Huntington’s disease, has been gained, relatively less information concerning how these genomic alterations then generate the disease pathophysiological phenotype has been gathered. Many neurodegenerative diseases are often considered as monogenomic phenomena, evolving research though has demonstrated that the phenotypic generation of the disease requires a molecular translation through a network of facilitating genes/proteins, i.e. the disease ‘signature’. This translating network therefore represents two important topics for translational neurobiological research, i) discovery of the crucial network nodes of genes/proteins that propagate and maintain the pathophysiology and, ii) generation of therapeutics whose network-targeted activity may exert an amplified and reinforced remedial action. The components (genes/proteins) of the molecular disease signature should comprise a minimal, but comprehensive, condensation of the disease process at a level that both facilitates a thorough appreciation of the disease but also provides a tractable framework for therapeutic development. Therapeutic intervention at the level of the molecular signature, will likely engage multiple endogenous signaling systems which will likely synergize to reinforce the potential therapeutic effects of the remedial agent.

Until recently, pharmacotherapeutics have been devised often with just single molecular targets in mind and have unfortunately often proven ineffective for a wide range of patients, especially for complex disorders such as Alzheimer’s disease. Hence, rather than considering disease as the perturbation of a single gene/protein factor, the appreciation of disease as the deformation of a complex network of factors in the disease signature would suggest that the most efficacious treatments would restore the balance of as many components as possible of the deformed signature to achieve its therapeutic effects. Targeting drug agents to G protein-coupled receptor (GPCR) systems has proven to be perhaps the most successful and broadly applicable therapeutic strategy. As GPCR signaling systems underpin and regulate nearly every physiological process their ability to regulate complex disease signatures is likely to be vital for future disease signature-based therapeutics. Recent discoveries have also indicated that with our increasing understanding of the potential complexities of GPCR signaling there appear to be many new avenues by which GPCR-targeted agents can control highly complex networks of functionally-related factors (Gesty-Palmer et al. 2013). To effect the development of signature-targeting agents we are employing multiple levels of receptor signaling analysis, i.e. proteomic and transcriptomic, to help us understand the subtle relationships between drug structure and eventual physiological therapeutic efficacy (Martin et al. 2012). With a comprehensive appreciation of the molecular signaling events that create the degenerative phenotype, it may also be possible to deploy this knowledge to understand, diagnose and treat many other prevalent complex diseases that impact neurological health such as Type 2 diabetes.

Publications

Genomic deletion of GIT2 induces a premature age-related thymic dysfunction and systemic immune system disruptionSiddiqui S, Lustig A, Carter A, Sankar M, Daimon C, Premont R, Etienne H, van Gastel J, Azmi A, Janssens J, Becker K, Zhang Y, Wood w, Lehrmann E, Martin J, Martin B, Taub D, Maudsley SAging-US, 9, 706-740, 2017
Nuclear GIT2 Is an ATM Substrate and Promotes DNA RepairLu D, Cai H, Park S, Siddiqui S, Premont R, Schmalzigaug R, Paramasivam M, Seidman M, Bodogai I, Biragyn A, Daimon C, Martin B, Maudsley SMOLECULAR AND CELLULAR BIOLOGY, 35, 1081-96, 2015
beta-arrestin-selective G protein-coupled receptor agonists engender unique biological efficacy in vivoGesty-Palmer D, Yuan L, Martin B, Wood w, Lee M, Janech M, Tsoi L, Zheng W, Luttrell L, Maudsley SMOLECULAR ENDOCRINOLOGY, 27, 296-314, 2013
Systems analysis of arrestin pathway functionsMaudsley S, Siddiqui S, Martin BProgress in Molecular Biology and Translational Science, 118, 431-67, 2013
Euglycemic agent-mediated hypothalamic transcriptomic manipulation in the N171-82Q model of Huntington disease is related to their physiological efficacyMartin B, Chadwick W, Cong W, Pantaleo N, Daimon C, Golden E, Becker K, Wood w, Carlson O, Egan J, Maudsley SJOURNAL OF BIOLOGICAL CHEMISTRY, 287, 31766-82, 2012

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How orbitrap helps VIB researchers expand the frontiers of science

11/07/2016 - ​Since its introduction in 2005, the Orbitrap mass spectrometer has quickly become a star in the research firmament. It has contributed to numerous significant breakthroughs in life sciences, especially in the fields of proteomics and metabolomics.

Stuart Maudsley

Stuart Maudsley

Research area(s)

Model organism(s)

Bio

​PhD: Univ. of Leeds, UK, 1996
Postdoc: Duke University, US, 1997-1999
PI: University of Edinburgh, UK, 2000-2004
Sr Scientist: National Institute on Aging, US, 2004-2006
Head of Receptor Pharmacology Unit, NIA, US, 2006-2013
VIB Group leader since Oct 2013​

Contact Info

VIB-UAntwerp Center for Molecular NeurologyGebouw VCampus Drie EikenUniversiteitsplein 1 2610 ANTWERPENRoute description