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Centre

Centre for Health, Ageing and Understanding Disease (CHAUD)

Unit(s) of assessment: Allied Health Professions, Dentistry, Nursing and Pharmacy

Research theme: Health and Wellbeing

School: School of Science and Technology

Overview

The Research Centre for Health, Ageing and Understanding Disease (CHAUD) encompasses research in Biomedical Sciences and Allied Health and aligns with the Health and Wellbeing strategic theme, the A03 Unit of Assessment and the Biosciences subject area here at NTU. Our research is structured around four themes covering various aspects of human health and chronic diseases, including cancers which are treatable but not curable, diabetes and other inflammatory conditions.

The research investigates the above disease processes with the aim of seeking prevention, incorporating lifestyle approaches and environmental impacts as well as therapies and utilising a wide range of methods and state-of-the-art technological platforms. The research is supported by “big data” analytical pipelines and bioinformatics expertise.

The research programmes tackle some of this century’s most urgent health challenges in an ageing population and include:

1) Understanding the different molecular and cellular mechanisms that underpin the development of chronic diseases, including diabetes, neurodegenerative disorders and musculoskeletal diseases

2) Unravelling cancer’s molecular complexity by harnessing the power of new technologies and the potential of data science and turning discovery into health by identifying biomarkers of therapeutic success and failure

3) Developing new mathematical approaches to understand complex systems and modelling mechanisms of mutations causing human genetic disease, sexually transmitted infections and cancer

4) Understanding the different mechanisms of microbial pathogenesis and host–microbiome interactions

5) Developing methods and materials (including bio-inspired compounds) for use as potential drugs to investigate biological processes and structures.

CHAUD includes the following Research Themes, which are all aligned with A03:

1) Cancer Biology, Immunology and Therapeutics (CBIT) – Our vision is to work collaboratively to improve health and wellbeing through fundamental and translational research into the molecular basis of cancer heterogeneity and tumour-host interactions and how these pathways can be targeted to yield better outcomes for many patients with cancer (personalised oncology). We conduct fundamental and translational research into a range of cancers, including acute leukaemia, breast, colorectal, pancreatic, liver, prostate and brain (glioblastoma multiforme). To address global challenges and unmet clinical needs in the cancer field, we are implementing and testing transformative therapeutic approaches, including antibody-based treatments and anti-tumour vaccination, that are tailored to specific, molecularly defined patient subgroups. These studies are supported by advanced bioinformatics and computational capabilities.

2) Diabetes, Chronic Diseases and Ageing (DCDA) - supports a multi-disciplinary translational team focussed on understanding the fundamental pathophysiology of type 2 diabetes, obesity, inflammatory based chronic diseases (Kidney, Asthma, Cardiovascular) and neuro-centred diseases of ageing (Alzheimer's, Parkinson’s and other neurological alterations). The research’s ambition is to investigate molecular mechanisms and dysfunction leading to disease to provide therapeutic insights and interventions for patient benefits

3) Antimicrobial Resistance, Omics & Microbiota (AROM) - incorporates classical microbiology (aerobic, microaerophilic, anaerobic), molecular biology, systems biology and bioinformatics. Members of the group work on mechanisms of microbial pathogenesis, factors influencing development of antimicrobial resistance, development of novel antimicrobials, population genomics and epidemiology, diversity of the human gut microbiota, host–microbiome interactions, predator–prey interactions, evolution of virulence, and plasmid biology and evolution.

4) Underpinning Technologies (UTec)

Biomathematics - develops new mathematical approaches based upon matrix computations, computational graph theory, Kolmogorov’s complexity, Bayesian inference, computational statistics, continuum mechanics and dynamical systems theory for: discovering important structural and functional features within large real-world networks and understanding complex systems, particularly those arising in biology; mining the data from post genomic technologies including, mass spectrometry, gene expression array and flow cytometry; modelling mechanisms of mutations causing human genetic disease and cancer; modelling soft tissue growth, sexually transmitted infections, and tissue engineering.

Therapeutic and Computational Chemistry - uses state of the art analytical and synthetic techniques to develop methods and materials to investigate biological processes and structures; bio-inspired compounds for use as potential drugs.

For all enquiries please contact the CHAUD Director, Professor Sergio Rutella.

External Funding

The Centre for Health, Ageing and Understanding Disease benefits from funding from the following external partners:

NIHR, Pancreatic Cancer UK, Wellcome Trust, The Headcase Cancer Trust, Roger Counter Foundation, Qatar National Research Fund, NanoString Technologies, MacroGenics, Kura Oncology, ImmuneBio International Ltd. UCB, NERC, Microsoft, UK Foreign and Commonwealth Office Zeiss, Innovate UK-KTP, The Headcase Cancer Trust, The Environment Agency.

Publications

Cancer Biology, Immunology and Therapeutics

Vadakekolathu J, Minden MD, Hood T, Church SE, Reeder S, Altmann H, Sullivan A, Viboch E, Patel T, Ibrahimova N, Warren SE, Arruda A, Liang Y, Smith TH, Foulds GA, Bailey MD, Gowen-MacDonald J, Muth J, Schmitz M, Cesano A, Pockley AG, Valk PJM, Löwenberg B, Bornhäuser M, Tasian SK, Rettig MP, Davidson-Moncada J, DiPersio JF, Rutella S. Immune landscapes predict therapeutic resistance, immunotherapy response and clinical outcomes in acute myeloid leukemia. Science Translational Medicine 2020; 12: eaaz0463.

Uy GL, Aldoss I, Foster MC, Sayre PH, Wieduwilt MJ, Advani AS, Godwin JE, Arellano ML, Sweet KL, Emadi A, Ravandi F, Erba HP, Byrne M, Michaelis LC, Topp MS, Vey N, Ciceri F, Carrabba MG, Paolini S, Huls GA, Jongen-Lavrencic M, Wermke M, Chevallier P, Gyan E, Recher C, Stiff PJ, Pettit KM, Löwenberg B, Church SE, Anderson E, Vadakekolathu J, Santaguida MT, Rettig MP, Muth J, Curtis T, Fehr E, Guo K, Zhao J, Bakkacha O, Jacobs K, Tran K, Kaminker P, Kostova M, Bonvini E, Walter RB, Davidson-Moncada JK, Rutella S, DiPersio JF. Flotetuzumab as salvage immunotherapy for refractory macute myeloid leukemia. Blood 2020 Sep 14: blood.2020007732.

Polytarchou C, Hatziapostolou M, Yau TO, Christodoulou N, Hinds PW, Kottakis F, Sanidas I, Tsichlis PN. Akt3 induces oxidative stress and DNA damage by activating the NADPH oxidase via phosphorylation of p47phox. Proc Natl Acad Sci USA 2020 Nov 17; 117 (46): 28806-15.

Koutsioumpa M, Hatziapostolou M, Polytarchou C, Tolosa EJ, Almada LL, Mahurkar-Joshi S, Williams J, Tirado-Rodriguez AB, Huerta-Yepez S, Karavias D, Kourea H, Poultsides GA, Struhl K, Dawson DW, Donahue TR, Fernández-Zapico ME, Iliopoulos D. Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming. Gut 2019 Jul; 68(7): 1271-86

Polytarchou C, Hommes DW, Palumbo T, Hatziapostolou M, Koutsioumpa M, Koukos G, van der Meulen-de Jong AE, Oikonomopoulos A, van Deen WK, Vorvis C, Serebrennikova OB, Birli E, Choi J, Chang L, Anton PA, Tsichlis PN, Pothoulakis C, Verspaget HW, Iliopoulos D. MicroRNA214 is associated with progression of ulcerative colitis, and inhibition reduces development of colitis and colitis-associated cancer in mice. Gastroenterology 2015 Oct; 149 (4): 981-92

Diabetes, Chronic Diseases and Ageing

Jackisch L, Kumsaiyai W, Moore JD, Al-Daghri N, Kyrou I, Barber TM, Randeva H, Kumar S, Tripathi G, McTernan PG. Differential expression of Lp-PLA2 in obesity and type 2 diabetes and the influence of lipids. Diabetologia 2018 May; 61(5): 1155-1166.

Schilperoort M, van Dam AD, Hoeke G, Shabalina IG, Okolo A, Hanyaloglu AC, Dib LH, Mol IM, Caengprasath N, Chan YW, Damak S, Miller AR, Coskun T, Shimpukade B, Ulven T, Kooijman S, Rensen PCN, Christian M. The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat. EMBO Molecular Medicine 2018 Mar; 10(3): e8047.

Adaikalakoteswari A, Vatish M, Alam MT, Ott S, Kumar S, Saravanan P. Low vitamin B12 in pregnancy is associated with adipose derived circulating miRs targeting PPARγ and insulin resistance. Journal of Clinical Endocrinology & Metabolism 2017 Nov 1; 102 (11): 4200-4209.

Austin M, Elliott L, Nicolaou N, Grabowska A, Hulse RP. Oncotarget 2017; 8 (44): 76606-76621.

Cripps MJ, Hanna K, Lavilla C, Sayers SR, Caton PW, Sims C, De Girolamo L, Sale C, Turner MD. Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake. Scientific Reports 2017; 7 (1): 13313.

Antimicrobial Resistance, Omics & Microbiota

Varney A, Smitten KL, Thomas JA, McLean S. Transcriptomic analysis of the activity and mechanism of action of a ruthenium (II)-based antimicrobial that induces minimal evolution of pathogen resistance. ACS Pharmacology and Translational Science 2021.

D'Amato A, Di Cesare Mannelli L, Lucarini E, Man AL, Le Gall G, Branca JJV, Ghelardini C, Amedei A, Bertelli E, Regoli M, Pacini A, Luciani G, Gallina P, Altera A, Narbad A, Gulisano M, Hoyles L, Vauzour D, Nicoletti C. Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients. Microbiome 2020; 8: 140.

Davies C, Taylor AJ, Elmi A, Winter J, Liaw J, Grabowska AD, Gundogdu O, Wren BW, Kelly DJ, Dorrell N (2019). Sodium taurocholate stimulates Campylobacter jejuni outer membrane vesicle production via down-regulation of the maintenance of lipid asymmetry pathway. Frontiers in Cellular and Infection Microbiology 9: 177.

McVicker G, Hollingshead S, Pilla G, Tang CM. Maintenance of the virulence plasmid in Shigella flexneri is influenced by Lon and two functional partitioning systems. Molecular Microbiology 2019; 111: 1355-66.

Hoyles L, Fernández-Real JM, Federici M, Serino M, Abbott J, Charpentier J, Heymes C, Luque JL, Anthony E, Barton RH, Chilloux J, Myridakis A, Martinez-Gili L, Moreno-Navarrete JM, Benhamed F, Azalbert V, Blasco-Baque V, Puig J, Xifra G, Ricart W, Tomlinson C, Woodbridge M, Cardellini M, Davato F, Cardolini I, Porzio O, Gentileschi P, Lopez F, Foufelle F, Butcher SA, Holmes E, Nicholson JK, Postic C, Burcelin R, Dumas ME. Molecular phenomics and metagenomics of hepatic steatosis in non-diabetic obese women. Nature Medicine 2018; 24: 1070-80.

Underpinning Technologies

Abdel-Fatah TMA, Agarwal D, Dong-Xu L, Russell R, Rueda OM, Liu K, Xu B, Moseley PM, Green AR, Pockley AG, Rees RC, Caldas C, Ellis IO, Ball GR, Chan SYT. SPAG5 as a prognostic biomarker and chemotherapy sensitivity predictor in breast cancer: a retrospective, integrated genomic, transcriptomic, and protein analysis. Lancet Oncology 2016; 17: 1004-18

Abdel-Fatah TMA, Ball G, Lee AHS, Pinder SE, Macmillan RD, Cornford E, Moseley PM, Silverman R, Price J, Latham B, Palmer D, Chan A, Ellis IO, Chan SYT. Nottingham Clinico-Pathological Response Index (NPRI) after neoadjuvant chemotherapy (Neo-ACT) accurately predicts clinical outcome in locally advanced breast cancer. Clinical Cancer Research 2015; 21 (5); 1056-62. DOI: 10.1158/1078-0432.CCR-14-0685

Tong DL, Boocock DJ, Dhondalay GKR, Lemetre C, Ball GR. Artificial Neural Network Inference (ANNI): A study on gene-gene interaction for biomarkers in childhood sarcomas. PLoS One 2014; 9 (7): e102483. DOI: 10.1371/journal.pone.0102483

Yu Pan, Glyn Bradley, Kevin Pyke, Graham Ball, Chungui Lu, Rupert Fray, Alexandra Marshall, Subhalai Jayasuta, Charles Baxter, Rik van Wijk, Laurie Boyden, Rebecca Cade, Natalie H Chapman, Paul Faser, Charlie Hodgman, Graham B Seymour: Network inference analysis identifies an APRR2-like gene linked to pigment accumulation in tomato and pepper fruits. Plant Physiology 2013; 161 (3): 1476-85. DOI:10.1104/pp.112.212654

Campeotto I, Francis Galaway F, Mehmood S, Barfod LK, Quinkert D, Kotraiah V, Phares TW, Wright KE, Snijders AP, Draper SJ, Higgins MK, Wright GJ. The structure of the cysteine-rich domain of Plasmodium falciparum P113 identifies the location of the RH5 binding site. mBio 2020; 11(5): e01566-20.

Facilities

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