Dr Tim Williams

Extracellular Vesicle Research Group

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Extracellular vesicles (including 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 extracellular vesicles 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 (miRNAs) 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 extracellular vesicles (EVs) that are relevant to renal and urinary tract disorders, namely; the utility of EVs as a source of biomarkers of renal diseases, and the clinical significance of the bactericidal activity of urinary exosomes/EVs, although I also collaborate with other groups to investigate the biomarker potential and pathophysiological roles of EVs in other contexts (cancer, transplant rejection, cardiac disease and pain).

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I am also interested in novel biomarkers for chronic kidney disease (CKD) in cats and urothelial cell carcinoma in dogs that might allow veterinarians to detect these diseases at an earlier stage. Our laboratory has recently identified differentially expressed proteins associated with EVs in cats with CKD and hypertension (Lawson et al, 2023) and identified urinary EV-associated miRNAs that are potential biomarkers for urothelial carcinoma in dogs (Karttunen et al, 2024).

Current group members:

Dr Tugdem Muslu-Ufik (Postdoctoral research associate)

Alex Currie (MPhil student)

Lanhui (Monica) Qui (PhD student)

Dr Dylan O' Toole (Senior Clinical Training Scholar)

Biography

Tim qualified from the University of Cambridge in 2007, and following a year working in small animal practice in west London, he undertook a PhD in the Feline Research Group at the Royal Veterinary College, London under the supervision of Professor Jonathan Elliott and Professor Harriet Syme. His research focused on feline geriatric medicine and, in particular, the effect of hyperthyroidism on renal function in cats. He received the Society for Comparative Endocrinology award for “Excellence in the Advancement in Veterinary Endocrinology” in 2011 and 2015. Tim joined the department in 2012 as Senior Clinical Training Scholar in Veterinary Clinical Pathology and subsequently became Lecturer in Clinical Pathology in September 2015 and Senior Lecturer/Associate Professor in 2019. He is a Fellow of the Royal College of Pathologists and a Diplomate of the European College of Veterinary Clinical Pathology.

Publications

Key publications:

Google Scholar - link to all publications

Extracellular vesicles in kidney disease - a veterinary perspective. Lawson JS, Williams TL. The Veterinary Journal (2024). In Press.

miR-182, miR-221 and miR-222 are potential urinary extracellular vesicle biomarkers for canine urothelial carcinoma. Karttunen JM, Kalmar L, Grant AJ, Ying J, Stewart S, Wang X, Karet Frankl FE, Williams TL. Scientific Reports. (2024) 14: 17967.

Towards optimised extracellular vesicle proteomics from cerebrospinal fluid. Kangas P, Nyman TA, Metsahonkala L, Burns C, Tempest R, Williams TL, Karttunen J, Jokinen TS. Scientific Reports. (2023) 13(1): 9564.

Urinary extracellular vesicles as a source of protein based biomarkers in feline chronic kidney disease and hypertension. Lawson JS, Syme HM, Antrobus PR, Kartunnen JM, Stewart SE, Karet Frankl FE, Williams TL. Journal of Small Animal Practice. (2023) 64: 3-11.

Excretory-secretory products from the 'brown stomach worm', Teladorsagia circumcincta, exert antimicrobial activity during in vitro growth assays. Rooney J, Williams TL, Northcote HM, Karet Frankl FE, Price DRG, Nisbet AJ, Morphew RM, Cantacessi C. Parasites and Vectors. (2022) 15: 354.

Parasitic helminths and the host microbiome - A missing 'extracellular vesicle-sized' link?. Rooney J, Northcote HM, Williams TL, Cortes A, Cantacessi C, Morphew RM. Trends in Parasitology. (2022) 38(9): 737-747.

Size-exclusion chromatography separation reveals vesicular and non-vesicular small RNA profiles differ in cell free urine. Kartunnen J, Stewart S, Kalmar L, Grant AJ, Karet Frankl FE, Williams TL. International Journal of Molecular Sciences. (2021) 22(9): 4881.

Making urinary extracellular vesicles a clinically tractable source of biomarkers for inherited tubulopathies using a small volume precipitation method: proof of concept. Williams TL, Bastos C, Faria N, Karet Frankl FE. Journal of Nephrology. (2020) 33(2): 383-386.

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.

Teaching and Supervisions

Teaching:

I am involved in didactic teaching of 4th and 5th year undergraduate veterinary students in the Clinical Pathology, Nephrology/Urology and Dermatology modules, and I regularly give small group seminars to our 6th year clinical rotation students. I am also the Module Organiser for the Principles of Clinical Pathology, Haematology and Oncology of the Lymphoid System (HOLS) and Nephrology and Urology modules.

I am the Deputy Director of Teaching (Curriculum) and Chair of the VetMB Clinical Curriculum Review Group (CCRG). I am also a member of the Faculty Board for the Department of Veterinary Medicine, the Department's Strategy and Executive Committee, Educational Quality Improvement Programme (EQIP) and Admissions Strategy Committees of the Department of Veterinary Medicine, and the Department's Pastoral Support Team. I contribute to the ongoing development of the pre-clinical course through the Medicine and Veterinary Medicine Course Review (MVMCR) Steering Committee and the Course Content sub-committee.

I am a fellow and Director of Studies in Veterinary Medicine (years 1-6) at Fitzwilliam College, and am the ECVCP residency programme director for clinical pathology.

Research supervision:

I supervise one Masters student, and am a co-supervisor/advisor to a PhD student in the St-John Smith laboratory (Dept of Pharmacology). I also supervise a number of undergraduate and intern/resident research projects.