Dr Smith graduated with Bachelor degrees in Medicine and Surgery from The University of Birmingham in 2003; his undergraduate medical training, also included a dedicated period of laboratory-based research for which he achieved an additional First Class Honours BMedSCi in pathological studies in 2002.
Completing his house officer year in Birmingham, he progressed to an appointment on to the Queen’s Medical Centre general medical SHO training Rotation in Nottingham. Admitted as member of the Royal College of Physicians in 2006 he returned to the West Midlands to join the renal medicine training rotation. Awarded a Wellcome Trust Clinical Training Fellowship he produced a doctoral thesis in 2012 that examines the role of the stromal cell protein CD248 in the pathogenesis of renal fibrosis.
Following appointment In March 2012 as a lecturer in renal medicine his time divides between developing his clinical training at the Queen Elizabeth Hospital renal unit, laboratory based research and clinical teaching.
His current research focus is in chronic kidney disease, stromal cell biology and the pathogenesis of renal fibrosis with a particular emphasis directed at identifying and developing the next generation of stromal cell targeted therapeutics. These studies are performed in collaboration with the Rheumatology research group in the state of the art Centre for Translational Inflammation Research.
Chronic kidney disease, stromal cell biology and the pathogenesis of renal fibrosis
Chronic kidney disease (CKD), a significant cause of human morbidity and mortality, is characterised by the replacement of functioning renal tissue by non-functioning fibrotic tissue because of injury. Resident renal stromal cells are pivotal in this process. Progress in research work into stromal cells has been restricted by a lack of identified cell specific proteins that could represent viable therapeutic targets.
By examine the role of the novel stromal pericyte protein CD248 in the pathogenesis of CKD. Dr Smith’s work has established that renal CD248 expression increases in the patients with CKD and CD248 levels can signal as an independent risk factor mapping progression to end stage renal failure that will require dialysis or transplantation.
Using an in vivo model, he has previously demonstrated that CD248 null mice acquire protection against the development of renal fibrosis. This phenotype is due to functional defects in stromal cells following the genetic deletion of CD248.
His current work in this field is to dissect the mechanism for this functional phenotype working towards the goal of developing the next generation of stromal cell targeting therapeutics.
Naylor AJ, Azzam E, Smith SW, Croft A, Poyser C, Huso DL, Gay S, Ospelt C, Cooper MS, Isacke, C, Goodyear S, Rogers M, Buckley CD. The MSC marker CD248 (Endosialin) is a negative regulator of bone formation. Arthritis Rheum 2012. (In press)
Smith SW, Duffield JS. The renal pericyte: A novel therapeutic target in tubulointerstitial fibrosis. Histol Histopathol. 2012. (In press)
Smith, S.W., S. Chand, and C.O. Savage. The biology of the renal pericyte. Nephrology Dialysis Transplantation (In press)
Hills CE, Siamantouras E, Smith SW, Cockwell P, Liu KK, Squires PE. TGFbeta modulates cell-to-cell communication in early epithelial-to-mesenchymal transition. Diabetologia. 2012;55(3):812-24.
Smith, S.W., K.S. Eardley, A.P. Croft, J. Nwosu, A.J. Howie, P. Cockwell, C.M. Isacke, C.D. Buckley, and C.O. Savage. 2011. CD248+ stromal cells are associated with progressive chronic kidney disease. Kidney Int 80:199-207.
Morris, H., M.D. Morgan, A.M. Wood, S.W. Smith, U.I. Ekeowa, K. Herrmann, J.U. Holle, L. Guillevin, D.A. Lomas, J. Perez, C.D. Pusey, A.D. Salama, R. Stockley, S. Wieczorek, A.J. McKnight, A.P. Maxwell, E. Miranda, J. Williams, C.O. Savage, and L. Harper. 2011. ANCA-associated vasculitis is linked to carriage of the Z allele of alpha antitrypsin and its polymers. Ann Rheum Dis 70:1851-1856.
Arulkumaran, N., S. Jawad, S.W. Smith, L. Harper, P. Brogan, C.D. Pusey, and A.D. Salama. 2011. Long-term outcome of paediatric patients with ANCA vasculitis. Pediatr Rheumatol Online J 9:12.