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Tim Williams

Biology of urinary exosomes and biomarkers of renal disease

Exosomes are nanovesicles released by cells, which contain proteins, mRNAs and microRNAs. In non-renal contexts they have various physiological functions including inter-cellular transfer of proteins and RNA, facilitation of immune responses, and modulation of the anti-apoptotic response. Urinary exosomes are also a rich source of potential biomarkers, since their membranes are composed of apical proteins from all nephron segments and they contain nucleic acid and protein cargo from the cell of origin. 

I am currently a visiting research fellow in the Karet laboratory (Cambridge Institute of Medical Research), and our laboratory has demonstrated that urinary exosomes are bactericidal (Hiemstra et al, 2014), and contain microRNAs capable of paracrine modulation of tubular membrane transporters in vitro (Gracia et al, 2017). The current focus of my research is to investigate two properties of exosomes that are relevant to renal and urinary tract disorders, namely; the utility of exosomes as a source of biomarkers of renal diseases, and the clinical significance of the bactericidal activity of urinary exosomes.

I am also interested in novel biomarkers for chronic kidney disease (CKD) in cats which might allow veterinarians to detect CKD at an earlier stage. This would allow managemental strategies to be instituted at an earlier stage when they might be more effective, thus reducing morbidity and mortality associated with CKD.

Key Publications

Google Scholar - link to all publications

Urinary exosomes contain microRNAs capable of paracrine modulation of tubular transporters in kidney. Gracia T, Wang X, Su Y, Norgett E, Williams TL, Moreno P, Micklem G, Karet Frankl FE. Scientific Reports. (2017) 7: 40601.

Serum cystatin C concentrations in cats with hyperthyroidism and chronic kidney disease. Williams TL, Dillon H, Syme HM, Elliott J, Archer J. Journal of Veterinary Internal Medicine. (2016) 30(4): 1083-1089.

Evaluation of urinary biomarkers for azotaemic chronic kidney disease in catsWilliams TL, Archer J.  Journal of Small Animal Practice. (2016) 27: 122-127.

Effect on renal function of restoration of euthyroidism in hyperthyroid cats with iatrogenic hypothyroidism. Williams TL, Elliott J, Syme HM. Journal of Veterinary Internal Medicine (2014) 28(4): 1251-1255

Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. Williams TL, Elliott J, Syme HM.  Journal of Veterinary Internal Medicine (2010) 24(5): 1086-92.

Survival and the development of azotemia after treatment of hyperthyroid cats. Williams TL, Peak KJ, Brodbelt D, Elliott J, Syme HM.  Journal of Veterinary Internal Medicine (2010) 24(4): 863-69.

Dr Tim Williams

University Lecturer in Clinical Pathology

tlw27@cam.ac.uk

 

    Plain English

    Kidney disease is a common condition of companion animals (especially cats) and humans. Unfortunately many of our current tests for kidney disease are not able to detect it until the disease is advanced, therefore the aim of my research is to identify tests that can identify kidney disease at an earlier stage. Urinary exosomes are small 'packages' released by kidney cells which are likely to contain substances that can act as markers of kidney disease. In addition, I am interested at investigating other functions of exosomes, such as their role in killing bacteria within the urinary tract.

    Funding

    BSAVA Petsavers

    Academy of Medical Sciences

    Tim is currently accepting PhD Student applications

    Tim is also available for consultancy