Denise Wootten

Dr

20062018
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Personal profile

Biography

Position

Research Fellow

Drug Discovery Biology

Monash Institute of Pharmaceutical Sciences

Faculty of Pharmacy and Pharmaceutical Sciences


Denise Wootten completed her PhD in 2008 at the University of Birmingham in the UK before moving to MIPs to join the DDB team. Her expertise is in the study of G protein-coupled receptors (GPCRs), particularly the family B subclass of GPCRs and the principal interest of her research is towards understanding the modes of their regulation in an effort to identify novel approaches for drug discovery. Her research interests encompass differential signalling, interaction of receptors with regulatory accessory proteins, allosterism and the structure and mechanism by which these GPCRs are activated.



Selected recent publications

1) Wootten D, Christopoulos A, Sexton PM. Emerging paradigms in GPCR allostery: implications for drug discovery. Nature Rev Drug Discov 12:630-644, 2013.

2) Sexton PM, Wootten D. Structural biology: meet the B family. Nature 499:417-418, 2013.

3) Wootten D, Simms J, Miller LJ, Christopoulos, A and Sexton PM. Polar transmembrane interactions drive formation of ligand-specific and signal pathway-biased Family B GPCR conformations. Proc Natl Acad Sci USA 110: 5211-5216, 2013.

4) Koole C, Savage EE, Christopoulos A, Miller LJ, Sexton PM, Wootten D. Signal bias, allosterism, and polymorphic variation at the GLP-1R: implications for drug discovery. Mol Endocrinol. 27(8):1234-44, 2013.

5) Harikumar KG*, Wootten D*, Pinon DI, Koole C, Ball AM, Furness SGB, Graham B, Dong M, Christopoulos A, Miller LJ, Sexton PM. Glucagon-like peptide-1 receptor dimerisation differentially regulates agonist signalling but does not affect small molecule allostery. Proc Natl Acad Sci USA 109: 18607-18612, 2012. *Equal first author.

6) Wootten D, Savage EE, Valant C, May LT, Sloop KW, Ficorilli J, Showalter AD, Willard FS, Christopoulos A, Sexton PM. Allosteric modulation of endogenous metabolites as an avenue for drug discovery. Mol Pharmacol. 82(2):281-90, 2012.

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Projects 2013 2018

Research Output 2006 2018

Two distinct domains of the glucagon-like peptide-1 receptor control peptide-mediated biased agonism

Lei, S., Clydesdale, L., Dai, A., Cai, X., Yang, F., Yang, D., Liang, Y-L., Koole, C., Zhao, P., Coudrat, T., Christopoulos, A., Wang, M-W., Wootten, D. & Sexton, P. M. 2018 In : Journal of Biological Chemistry. 293, 24, p. 9370–9387 19 p.

Research output: Contribution to journalArticle

Allostery and Biased Agonism at Class B G Protein-Coupled Receptors

Wootten, D., Miller, L. J., Koole, C., Christopoulos, A. & Sexton, P. M. 11 Jan 2017 In : Chemical Reviews. 117, 1, p. 111-138 28 p.

Research output: Contribution to journalReview Article

Characterization of signal bias at the GLP-1 receptor induced by backbone modification of GLP-1

Hager, M. V., Clydesdale, L., Gellman, S. H., Sexton, P. M. & Wootten, D. 4 Feb 2017 (Accepted/In press) In : Biochemical Pharmacology. 10 p.

Research output: Contribution to journalArticle

Co-expressed class B G protein-coupled secretin and GLP-1 receptors self- and cross-associate: impact on pancreatic islets

Harikumar, K. G., Lau, S., Sexton, P. M., Wootten, D. & Miller, L. J. 1 Jun 2017 In : Endocrinology. 158, 6, p. 1685-1700 16 p.

Research output: Contribution to journalArticle

Improving virtual screening of G protein-coupled receptors via ligand-directed modeling

Coudrat, T., Simms, J., Christopoulos, A., Wootten, D. & Sexton, P. M. 1 Nov 2017 In : PLoS Computational Biology. 13, 11, 40 p., e1005819

Research output: Contribution to journalArticle

Open Access
File

Activities 2011 2011

  • 1 Submissions to industry or govt committees, commissions and inquiries

Drug Discovery Biology

Wootten, D. L. (Member)
1 Dec 2011

Activity: Submissions to industry or govt committees, commissions and inquiries