Dr John S. Young

Biography

• Ph.D. Neuroscience. University of Cambridge, 2000 - 2004
• B.Sc. (Hons) Biology with year-in-Industry. University of York, 1996 - 2000

• Aug. 2008 – Feb. 2009. Wellcome Trust VIP Post-Doctoral Research Fellow, Department of Pharmacology, University of Oxford, UK.
• Jan. – July 2008. International Scholar, Department of Cell Biology and Physiology, University of Nevada, Reno, USA.
• Jan. 2005 – Dec. 2007. Post-Doctoral Research Scientist, Department of Pharmacology, University of Oxford, UK.
• Aug. – Dec. 2004. Project Management of the 2004 Royal Institution ‘Christmas Lectures’. See: [here], [here] and [here].
• Oct. 2001 – July 2004. Laboratory Demonstrator and Tutor; during Ph.D. studies, University of Cambridge
• July 1998 – Sept. 1999. Sandwich Student; Central Science Laboratories (DEFRA), York, UK.
• July 1997 – Sept. 1997. Laboratory Demonstrator and Technician for the Open University ‘Brains and Behaviour’ summer school, based at the University of York, UK.

Research Interests

My research focuses on studying signalling mechanisms that are active in the normal and diseased bladder. The aims of this research are to identify new drug targets and therefore better treatment of common, debilitating diseases.

AgeUK Research Fellowship

Urinary incontinence affects 1 in 5 men and half of all women over the age of 65. The problem gets worse with age and, since the population of the UK is ageing, this problem is increasing. Urinary incontinence has significant impact on quality of life, exerts a huge strain on carers and frequently leads to the premature admittance of patients into care homes.

Incontinence is a symptom of many diseases, and this study focuses on the most common; overactive bladder. The current first-line treatment for overactive bladder is a class of drugs called anti-cholinergics. Unfortunately, these are ineffective in around half of patients and have significant side-effects resulting in two-thirds of patients discontinuing treatment. Alternative treatment options are limited, have variable success, are associated with unpleasant side effects and poor tolerability.

The aim of my AgeUK Research Fellowship is to understand why the symptoms of some patients are non-responsive to anti-cholinergics in order to provide the foundation for producing more effective overactive bladder treatment.

Our study will influence the clinical treatment of the large proportion of overactive patients for whom anti-cholinergic treatment is ineffective, ultimately enabling the definition of patient-appropriate treatment groups and providing the basis for the development of new therapeutic options to treat this common, debilitating condition.

Progress to date:

1. A method to stretch the lining of the bladder that I personally developed was applied to determine the previously unknown mode-of-action of the most widely-used class of drug for the treatment of urinary incontinence. This work has recently been accepted for publication - Young et al. Inhibition of stretch-evoked ATP release from bladder mucosa by anti-cholinergic agents. British Journal of Urology International. In Press.

2. Since collection of human bladder biopsies began (April 2011), many new findings relating to the pathology of overactive bladder have been identified. Such findings are of great translational value and have the potential to impact patient care.

Additional studies

In addition to my own Research Fellowship, I am a co-investigator on an EU FP7 (‘INComb’) grant (01 Dec. 2008 – 30 Nov 2011; £249,667) and projects sponsored by Boston Scientific (01 Nov 2011 – TBC; £45,153) and Takeda (01 Apr 2011 – 31 Dec 2011; £40,991).  I successfully completed a project sponsored by Pfizer (01 July 2008 – 31 Dec 2010. £43,056).

Publications

1. Young JS, Johnston L, Soubrane C, McCloskey KD, McMurray G, Eccles R, Fry CH. The passive and active contractile properties of the neurogenic, underactive bladder. British Journal of Urology International. In Press.

2. Fry CH, Young JS, Jabr RI, McCarthy C, Ikeda Y, Kanai AJ. Modulation of spontaneous activity in the overactive bladder - the role of P2Y agonists. American Journal of Physiology. In Press. [abstract]

3. Young JS, Matharu R, Carew MA, Fry CH. Inhibition of stretch-evoked ATP release from bladder mucosa by anti-cholinergic agents. British Journal of Urology International. In Press. [abstract]

4. Meng E,Young JS, Cha TL, Sun GH, Yu DS, Brading AF. Neuronal-derived Nitric Oxide Modulates the Activity of Mouse Detrusor Smooth Muscle. Neurourology and Urodynamics. In Press. [abstract]

5. Johnston L, Cunningham RMJ, Young JS, Fry CH, McMurray G, Eccles R, McCloskey KD. Altered distribution of interstitial cells and innervation in the rat urinary bladder following spinal cord injury. Journal of Cellular and Molecular Medicine. In Press. [abstract]

6. Kobayter S, Young JS, Brain KL. (2012). Prostaglandin E₂ induces spontaneous rhythmic activity in mouse urinary bladder independently of efferent nerves. British Journal of Pharmacology 165:401-13. [abstract]

7. Fry CH, Bayliss M, Young JS, Hussain M. (2011). The influence of age and bladder dysfunction on the contractile properties of isolated human detrusor smooth muscle. British Journal of Urology International 108:E91-6. [abstract]

8. Valeri A, Brain KL, Young JS, Sgaragli G, Pessina F. (2009). Effects of 17β-estradiol on rat detrusor smooth muscle contractility. Experimental Physiology 94:834-846. [abstract] [PDF]

9. Young JS, Amos RJ, Brain KL. (2009). Focal Ca2+ transient detection in smooth muscle. Journal of Visualized Experiments 28. doi: 10.3791/1247. [abstract] [PDF]

10. Young J., Meng E, Cunnane TC, Brain KL. (2008). Spontaneous purinergic neurotransmission in the mouse urinary bladder. Journal of Physiology 586: 5743-5755. [abstract] [PDF]

11. Zhu H-L, Brain KL, Aishima M, Shibata A, Young JS, Sueishi K, Teramoto N. (2008). Actions of Two Main Metabolites of Propiverine (M-1 and M-2) on Voltage-Dependent L-Type Ca2+ Currents and Ca2+ Transients in Murine Urinary Bladder Myocytes. Journal of Pharmacology and Experimental Therapeutics 324: 118-127. [abstract] [PDF]

12. Meng E, Young JS, Brading AF. (2008). Spontaneous activity of mouse detrusor smooth muscle. Neurourology and Urodynamics 27(1): 79-87. [abstract] [PDF]

13. Young JS, Brain KL, Cunnane TC. (2007). On electrically-evoked neurotransmission in mouse isolated vas deferens smooth muscle. Neuroscience 148: 82-91. [abstract] [PDF]

14. Young JS, Brain KL, Cunnane TC. (2007). The origin of the skewed amplitude distribution of spontaneous excitatory junction potentials in poorly coupled smooth muscle cells. Neuroscience 145: 153-161. [abstract] [PDF]

15. Huang WC, Young JS, Glitsch MD. (2007). Changes in TRPC channel expression during postnatal development of cerebellar neurons. Cell Calcium 42: 1-10. [abstract] [PDF]

16. Young JS, Peck LS, Matheson T. (2006). The effects of temperature on walking and righting in temperate and Antarctic crustaceans. Polar Biology 29: 978-987. [abstract] [PDF]

17. Young JS, Peck LS, Matheson T. (2006). The effects of temperature on peripheral neuronal function in eurythermal and stenothermal crustaceans. Journal of Experimental Biology 209: 1976-1987. [abstract] [PDF]

18. Young J (2002). Physiological control of behaviour at low temperatures. Physiology News 49 18.

Review articles

Madersbacher H, Cardozo L, Chapple C, Abrams P, Toozs-Hobson P, Young JS, Wyndaele JJ, De Wachter S, Campeau L, Gajewski JB. (2012). What are the causes and consequences of bladder overdistension? ICI-RS 2011. Neurourol Urodyn. 31(3):317-21. [abstract]

Fry CH, Young JS. (2010). The physiology and pharmacology of the lower urinary tract. Surgery 28: 317-322. [abstract]

Fry CH, Meng E, Young JS. (2009). The physiological function of lower urinary tract smooth muscle. Autonomic Neuroscience 154:3-13. [abstract] [PDF]

Book chapters

Fry CH, Chacko S, Chess-Williams R, de Wachter S, Kanai AJ, Takeda M, Young JS. Committee 2 report – Cell Biology. (2012). In: Abrams P, Cardozo L, Khoury S, Wein A. Incontinence 5th Edition. In Press.

Conferences – oral communications

Young JS, Meng E, Cunnane TC, Brain KL (2008). Spontaneous ATP release from nerves is the predominant determinant of spontaneous action potentials in the mouse urinary bladder. Physiological Society's Vascular & Smooth Muscle Physiology Themed Meeting at King's College London, 15-17 December 2008.

Young JS (2001). Temperature dependence of neuronal function in marine isopods. Departmental Symposium, University of Cambridge.

Conferences – poster presentations and proceedings

Young J, Johnston L, McMurray G, Eccles R, McCloskey K, Fry C. The physiological properties of the decompensated, spinal cord injured bladder. International Continence Society, Glasgow, 29 Aug – 2 Sept 2011.

Wu C, Sui G, Matharu R, Fry C, Montgomery B, Young J. Muscarinic modulation of urothelial ATP release and its paracrine action. International Continence Society, Glasgow, 29 Aug – 2 Sept 2011.

Young JS, Meng E, Cunnane TC, Brain KL (2008). Spontaneous ATP release from nerves is the predominant determinant of spontaneous action potentials in the mouse urinary bladder. Physiological Society's Vascular & Smooth Muscle Physiology Themed Meeting at King's College London, 15-17 December 2008.

Meng E, Young JS, Brading AF. (2008). Differential roles of neuronal- and urothelium-derived NO in the Modulation of the Spontaneous Activity of Mouse Detrusor Smooth Muscle. International Continence Society, October 20-24, 2008.

Kennard JAG, Young JS, Brain KL. (2008). Non-genomic effects of testosterone on contraction in the mouse vas deferens. Abstracts of the EPHAR (Federation of the European Pharmacological Societies) 2008 Congress. Manchester, United Kingdom. July 13-17, 2008. Fundamental & clinical pharmacology 22 Suppl 2, 1-131.

Young JS, Brain KL, Cunnane TC. (2007). Measures of purinergic neurotransmission reveal variable effective packet size. Autonomic Neuroscience: Basic and Clinical 135: 116-117.

Meng E, Young JS, Brading AF. (2007). The effect of the urothelium on the spontaneous activity of the mouse detrusor smooth muscle. BJU Int 99 (s4), 45–55.

Meng E, Young JS, Brading AF. (2007). The Effect of the Urothelium on the Detrusor Smooth Muscle. European Urology Supplements 6, 37-37.

Young JS, Peck LS, Matheson T. (2003). Temperature sensitivity of motor behaviour and its neurophysiological control in marine crustaceans from different thermal environments. Proceedings of the 29th Göttingen Neurobiology Conference, p371.

Young JS, Peck LS, Matheson T. (2003). Effects of temperature on crustacean behaviour and neurophysiology. Comparative Biochemistry and Physiology A 134 (3, suppl.), S 72.

Young JS, Matheson T. (2001). Temperature dependence of neuronal function in marine isopods. XXXIV IUPS 2001, 1775.

Young JS, Matheson T. (2001). Temperature dependence of neuronal function in eurythermal and stenothermal crustacea. 6th International Congress of Neuroethology, Bonn, 192.

Invited lectures

The untold consequences of ageing: what goes wrong and what can we do about it? Denbigh School, Milton Keynes (2010); School and College Science and Engineering Lectures, University of Surrey (2011).

How the nervous system influences the body and its functions. Denbigh School, Milton Keynes (2009).

Measures of neurotransmission reveal variable effective packet size. Dundalk Institute for Technology, Republic of Ireland (2007).

Temperature dependence of neuronal function in marine isopods. British Antarctic Survey, Cambridge (2003).

Teaching

Affiliations

I am a member of the International Consultation on Incontinence.

Refereeing
I have refereed manuscripts for the following journals:

• The British Journal of Pharmacology
• International Urogynecology
• Journal of Applied Physiology
• Experimental Physiology

I am a Panel Member and Reviewer for Nuffield Foundation Undergraduate Research Bursaries.