Staff Profile
Dr Kate Madden
NUAcT Fellow: Drug Discovery
- Email: kate.madden@ncl.ac.uk
- Address: Chemistry
School of Natural and Environmental Sciences
Bedson Building
Newcastle University
Newcastle upon Tyne
NE1 7RU
Background
Kate (Katrina) Madden is a Newcastle University Academic Track Fellow in Drug Discovery, within the School of Natural and Environmental Sciences. Her research interests centre on drug discovery for fine control of the immune system, particularly in neurological diseases. This work is interdisciplinary, combining medicinal chemistry and in vitro cell biology, and also involves working within the Faculty of Medical Sciences. The goal of her fellowship is to provide the foundations for new drug discovery programmes in neurodegenerative disease which translate to bringing real benefit to patients.
Before taking up this post Kate held Postdoctoral Research Associate posts at the University of Oxford, where she worked on drug discovery programmes in neurodegenerative disease and acute myeloid leukaemia, in addition to helping to establish new enzyme-based chemical synthesis methods for medicinal chemistry. She also held a Part-Time Stipendiary Lectureship in Organic Chemistry at Jesus College, University of Oxford.
Qualifications
PhD, Synthesis of Polyene Natural Products, Durham University, supervisor Professor Andy Whiting, 2017
MChem with Industrial Experience, Durham University and AstraZeneca R&D Oncology, 2013
Research within the group aims to evaluate the potential of different approaches to drugging the immune system in the brain. We do this by assessing the effect of small molecules on specific protein targets (target-based drug discovery), and on whole cells (phenotypic drug discovery). We are currently studying the potential to drug one specific immune cell type in the brain, microglia. These cells are part of the innate immune system, acting as messengers to control the body's immune response, and play a key role in triggering and resolving inflammation. It is our hope that by achieving fine control over their function we can tune the behaviour of the immune system into the most beneficial role for treating neurodegenerative and neurological diseases. Our research projects are aligned with this central goal:
Small molecules to inhibit interferon signalling in neuroinflammatory disease
This project aims to reduce the body's reaction to the inflammatory chemical interferon, with the hoping of treating neurological conditions with an inflammatory component. There are specific 'interferonopathies' which present with neurodegeneration which we hope to treat. In addition, increasing evidence is suggesting that interferon signalling plays a key role in neuroinflammation in neurodegenerative diseases such as Alzheimer's Disease (AD) and amyotrophic lateral sclerosis (ALS).
Collaborations: Dr Christopher Duncan (Newcastle University), Professor Sophie Hambleton (Newcastle University), Dr Catherine Adamson (University of St Andrews)
New ways to target complement with small molecules in the brain
This project aims to develop new disrupters of the complement pathway by targeting specific protein-protein interactions with small molecules that possess good properties for passing through the blood-brain barrier. By doing this, we hope to reduce excessive inflammation and neurodegeneration in the brain.
Collaborations: Dr Agnieszka Bronowska (Newcastle University), Professor Claire Harris (Newcastle University)
Understanding and harnessing the effect of anti-inflammatory small molecules on microglial phenotype
This project aims to understand more about known anti-inflammatory compounds, linking the overall effect on neuroinflammation with an exact microglial phenotype that we can then target in future drug discovery programmes. We aim to generate robust chemical tools, and identify new molecular targets for neurodegenerative disease.
Collaborations: Dr Ian Wood (University of Leeds)
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Articles
- Xu S, Kondal MD, Ahmad A, Zhu R, Fan L, Zaborniak P, Madden KS, de Souza JV, Bronowska AK. Mechanistic Investigation of the Androgen Receptor DNA-Binding Domain and Modulation via Direct Interactions with DNA Abasic Sites: Understanding the Mechanisms Involved in Castration-Resistant Prostate Cancer. International Journal of Molecular Sciences 2023, 24(2), 1270.
- Chatzopoulou M, Madden KS, Bromhead LJ, Greaves C, Cogswell TJ, Da Silva Pinto S, Galan SRG, Georgiou I, Kennedy MS, Kennett A, Apps G, Russell AJ, Wynne GM. Pilot Study to Quantify Palladium Impurities in Lead-like Compounds Following Commonly Used Purification Techniques. ACS Medicinal Chemistry Letters 2022, 13(2), 262-270.
- Jackson TR, Vuorinen A, Josa-Cullere L, Madden KS, Conole D, Cogswell TJ, Wilkinson IVL, Kettyle LM, Zhang D, O'Mahony A, Gracias D, McCall L, Westwood R, Terstappen GC, Davies SG, Tate EW, Wynne GM, Vyas P, Russell AJ, Milne TA. A tubulin binding molecule drives differentiation of acute myeloid leukemia cells. iScience 2022, 25(8), 104787.
- Josa-Culleré L, Madden KS, Cogswell TJ, Jackson TR, Carter TS, Zhang D, Trevitt G, Davies SG, Vyas P, Wynne GM, Milne TA, Russell AJ. A Phenotypic Screen Identifies a Compound Series That Induces Differentiation of Acute Myeloid Leukemia Cells In Vitro and Shows Antitumor Effects In Vivo. Journal of Medicinal Chemistry 2021, 61, 15608-15628.
- Madden KS, Jokhoo HRE, Conradi FD, Knowles JP, Mullineaux CW, Whiting A. Using Nature’s antioxidants as templates: Studies of synthetic xanthomonadin analogues and realising their potential as antioxidants. Organic and Biomolecular Chemistry 2019, 17, 3752-3759.
- Madden KS, Knowles JP, Whiting A. A low temperature, vinylboronate ester-mediated, iterative cross-coupling approach to xanthomonadin polyenyl pigment analogues. Tetrahedron 2019, 75(45), 130657.
- Madden KS, Laroche B, David S, Batsanov AS, Thompson D, Knowles JP, Whiting A. Approaches to styrenyl building blocks for the synthesis of polyene xanthomonadin and its analogues. European Journal of Organic Chemistry 2018, 2018(38), 5312-5322.
- Madden KS, David S, Knowles JP, Whiting A. Heck-Mizoroki coupling of vinyliodide and applications in the synthesis of dienes and trienes. Chemical Communications 2015, 51(57), 11409-11412.
- Blades K, Box MR, Dickinson S, Lamont GM, Madden K, McCoull W, Williams JD, Kemmitt PD. Synthesis of 3-(hetero)aryl tetrahydropyrazolo[3,4-c] pyridines by Suzuki-Miyaura cross-coupling methodology. Journal of Organic Chemistry 2014, 79(16), 7682-7688.
- Hennessy EJ, Blades K, Box MR, Chuaqui C, Dowling JE, Davies CD, Ferguson AD, Goldberg FW, Howe NJ, Kemmitt PD, Lamont GM, Madden K, McWhirter C, Varnes JG, Ward RA, Williams JD, Yang B, McCoull W. Identification and optimisation of 7-azaindole PAK1 inhibitors with improved potency and kinase selectivity. MedChemComm 2014, 5(10), 1533-1539.
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Reviews
- Jorg M, Madden KS. The right tools for the job: the central role for next generation chemical probes and chemistry-based target deconvolution methods in phenotypic drug discovery. RSC Medicinal Chemistry 2021, 12(5), 646-665.
- Madden KS, Mosa FA, Whiting A. Non-isoprenoid polyene natural products-structures and synthetic strategies. Organic and Biomolecular Chemistry 2014, 12(40), 7877-7899.