R H Smallwood BSc MSc PhD FREng HonFRCP FIEE FInstP

Professor of Computational Biology
Director of Research and Innovation (Healthcare across the Disciplines)

Introduction

Career: my career, following University (BSc Physics UCL 1966, MSc Solid State Physics Lancaster 1967), can be considered in four periods. First, twelve years in the NHS, during which I was awarded a PhD (Medical Physics Sheffield 1976), progressed from Basic Grade Physicist to Top Grade Physicist, and was primarily involved in research and development. Second, ten years in the NHS which were dominated by service development and management, at the end of which I was acting as Business Manager for the Directorate of Medical Physics and Clinical Engineering. Third, from about 1990, I re-established a research reputation and gained a Personal Chair (Professor of Medical Engineering) whilst still employed by the NHS (1995), and then moved to the University of Sheffield as Head of Medical Physics and Engineering in the Medical School (1996). In Medical Physics and Engineering, my major achievement was to take the department from a 2C rating in 1996 as a component part of a much larger unit to a 5A stand-alone rating in the 2001 Research Assessment Exercise. I was elected a Fellow of the Royal Academy of Engineering in 2001 and and Honorary Fellow of the Royal College of Physicians in 2002.  The fourth period commenced with changing my research interests from medical engineering to computational biology, and moving to Computer Science as Professor of Computational Biology, whilst still retaining a position in the Medical School. From 2003 to 2008 I was the University's Director of Research for Engineering, and from August 2009 I have been the University's Director of Research & Innovation for Healthcare across the Disciplines.

Teaching: I have established three degree courses at Sheffield (MSc in Medical Physics and Clinical Engineering, BSc/MPhys in Physics with Medical Physics, BEng/MEng in Biomedical Engineering). The department’s teaching was assessed together with Physics and Astronomy, and was rated Excellent. I was a QAA Specialist Subject Reviewer for Physics and Astronomy. In Computer Science I have taught an Advanced Research Topic (an Introduction to Computational Systems Biology), shared the oversight of the Darwin group projects, and taught COM 2040 on Professional Issues.

Professional: I am a Fellow of the Institution of Electrical Engineers, the Institute of Physics, and  was a Fellow of the Institute of Physics and Engineering in Medicine. I was one of the first six non-medics to be elected an Affiliate of the Royal College of Physicians. I have been continuously involved in professional activities, principally with the IEE and IPEM, for the past 25 years. I am a past President of IPEM. I am a member of the EPSRC Peer Review College.

Research achievements

• Paraplegic Urology: my introduction to research on patients was in collaboration with a urologist, David Thomas, and the goal was to explain the natural history of bladder function following transection of the spinal cord. At the time, the major cause of death in paraplagics who survived their spinal injury was kidney failure. Our two year study established that dysinergia (simultaneous contraction of the bladder and the pelvic floor) gave rise to very high pressures within the bladder, resulting in reflux which destroyed the kidneys. This finding changed bladder management in paraplegics, and effectively ended this cause of mortality. I continued to have an involvement in the management of the paraplegic bladder until David Thomas retired in 2001.
• Gastrointestinal motility: a major interest of Professor (later Sir) Herbert Duthie, head of the Department of Surgery at Sheffield, was the electrical activity and motility of the human gastrointestinal tract. The slow wave activity (<0.2 Hz) throughout gut, and the associated motility, were little known or understood in the 1970s. Bert Duthie lead an internationally-recognised multi-disciplinary team. We used implanted, mucosal and surface electrodes to measure the electrical activity throughout the gut, and I established the origin of signals recorded non-invasively using surface electrodes. Our pioneering modelling of electrical activity, using an analogue van der Pol oscillator model (64 oscillators) that I designed, demonstrated that a pacemaker region was not required to generate the slow waves observed in the gut - they are an emergent property of coupled non-linear oscillators.
• Ultrasonic Doppler: in the mid-1970s, ultrasonic Doppler techniques were in their infancy. I developed instrumentation for blood velocity measurement - quadrature demodulation for resolving simultaneous forward and reverse flow and a real-time frequency analyser to display flow waveforms. I established one of the first Vascular Laboratories in the UK, with a consequent reduction in the morbidity and mortality caused by angiography. For a period of about ten years (until commercial equipment became available) the Vascular Laboratory used equipment designed by myself.
• Red cell physics: a former colleague, Tony Trowbridge, developed a theoretical model of blood flow, considering it as a two phase liquid. I devised and implemented a precision measurement of red cell sedimentation to validate the theory.
• Electrical Impedance Tomography: one of the earliest practical demonstrations of electrical impedance tomography was made using my forearm as the experimental object, and I was subsequently involved to a limited extent in the design of the instrumentation. I applied the technique in measurements on the gastro-intestinal tract, but my first major contribution was the first three-dimensional reconstruction of electrical impedance tomography images, utilising pseudo-inversion of a sensitivity matrix (funded by Action Research).
• Scanning Thermal Microscopy: I subsequently ported the 3-d reconstruction technique to 3-d image formation in scanning thermal microscopy. In this case, depth information is obtained by modulating the thermal signal at different frequencies. Explicit inversion of the sensitivity matrix (estimated to take about one thousand years!) was avoided by using a Best Linear Estimator technique developed by a commercial partner (funded by EU FP5).
• Virtual Reality trainers for surgery: when a colleague, Tony Trowbridge, died in 1997, I took over two of his EPSRC grants, concerned with the development of a Virtual Reality simulator for training surgeons in knee arthroscopy. This programme is continuing (with a third successive EPSRC grant) to incorporate haptic feedback and validate training effects.
• Neonatal physiology: information related to physiology is difficult to obtain from neonates and young children, as they are not able to co-operate. We have had a long-term interest in respiration in neonates, and have developed Electrical Impedance Tomography equipment specifically for this application, produced the first EIT images of neonatal lungs, and have shown that developmental changes in neonatal lungs can be monitored (funded by EPSRC).
• Electrical impedance spectroscopy: a four electrode measurement technique can be used to characterise tissue. The technique was developed to screen for pre-malignant and malignant changes in the cervix (Brian Brown is the leader for cervical screening), and has been shown to have the same sensitivity and specificity as cervical smears. We are exploring the possibility of a major trial in India. I extended this to screening in other epithelial tissues (esophagus and bladder) (funded by EPSRC).
• Development of normal and malignant epithelial tissue: I was awarded the first EPSRC Platform grant in the Life Sciences Interface area to support a programme of research into physical methods of identifying malignant cells in epithelial tissue, and computational modelling of development, wound healing and malignancy in epithelial tissue (the Epitheliome).
• The Epitheliome: we were awarded £2m by EPSRC to further develop the computational modelling of development, wound healing and malignancy in epithelial tissue. The 5-year project has now finished - there is more information about the project, publications, and continuing work on the Epitheliome Project page.
  
• Optical Coherence Tomography: we were awarded £700k by BBSRC to develop novel semiconductor light sources for ultra-high resolution optical coherence tomography.
• Skin modelling: I have a commercial contract to continue the work on computational models of skin.
• AirPROM started on February 1st 2011 - see my home page for more details and links. My work package concentrates on airway remodelling in Asthma and COPD following challenge by allergens and irritants.
  

Research funding

MRC. E A Trowbridge & R H Smallwood. The characteristics of fatigue-induced failure in pericardial heterografts. 1/10/86 to 30/9/88. £32,444 (initial funding) and £19,945 (1 year extension to above)

University Research Fund. R H Smallwood, E A Trowbridge & C E Crofts. The mechanical properties and failure modes of compliant biological composites. 22/12/88. £3000

MRC. D G Thomas, R H Smallwood & N W Read. Control of bladder and bowel function in paraplegics by sacral root stimulation. 17/10/88-30/9/90. £82,659.

Special Trustees to the Former United Sheffield Hospitals. N W Read & R H Smallwood. Control of bladder and bowel function in paraplegics by sacral root stimulation. 20/7/88. £11,000.

Bardhan Research Trust. R H Smallwood. The measurement of gastro-esophageal reflux and gastric acid using electrical impedance tomography. 1/10/92-30/9/96. £45,000.

Action Research. R H Smallwood, D C Barber and W B Tindale. The application of three-dimensional Electrical Impedance Tomography in the investigation of ventilation-perfusion defects. £91,001. 1/10/94-30/9/97.

Deutsche Forschungsgemeinschaft. (R H Smallwood), G Hahn and I Sipinkovà. Equipment for collaborative study of ventilation in pigs using electrical impedance tomography. 1/95. £19,000. (Equipment grant from the DfG for collaborative work in Göttingen).

MRC. R H Smallwood, B H Brown and R A Primhak. Pilot studies of electrical impedance tomography (EIT) of the chest in infants. 1/2/95-31/1/96. £24,900.

Trent Regional Health Authority. R A Primhak, R H Smallwood and B H Brown. Pilot studies of electrical impedance tomography (EIT) of the chest in infants. 1/4/95-30/9/96. £45,600.

EPSRC. B H Brown, D C Barber and R H Smallwood. Electrical impedance spectra of biological tissues. 1/10/96-31/12/99. £117,707.

EPSRC. R H Smallwood. A multi-media arthroscopic simulator of surgical procedures. 1/10/96-30/9/99. £123,305

ESPRIT. R H Smallwood. TASM: HPCN-enabled tomographic analysis with scanning microscopy. 1/6/98-30/11/99. €277,800.

EPSRC GR/M36205. B H Brown, R H Smallwood, R A Primhak. Electrical impedance tomographic spectroscopy (EITS) measurement from and modelling of neonatal lungs. 1/10/98-30/9/01. £211,824

EPSRC GR/M60859. R H Smallwood, K D Bardhan, B H Brown, T J Stephenson, C J Stoddard, D R Hose, J M R Weaver. Optimal electrical impedance techniques for identifying pre-cancerous tissue. 1/12/99-30/11/2002. £243,313

EPSRC GR/R16815. P V Lawford, S Mac Neil, E Freedlander, D R Hose, R H Smallwood. Measurement of tension generated by cultured human keratinocytes. 1/01/01-30/06/01. £27,881.

EPSRC GR/N23974. R H Smallwood, P J Harley, B Davies, H P Wynn, D Bickerstaff. Innovative haptics for risk mediation in VR Arthroscopic training. 1/7/01-30/6/04. £366,188

EPSRC GR/N25459. B Davies, R H Smallwood, P J Harley, H P Wynn, D Bickerstaff. Innovative haptics for risk mediation in VR Arthroscopic training. 1/7/01-30/6/04. £219,673 (Imperial College)

EPSRC GR/R42320. F C Hamdy, R H Smallwood. Electrical impedance spectroscopy of urothelium. 1/6/2001-31/5/2002. £51,463

EPSRC GR/R48032. R H Smallwood, F C Hamdy, J Southgate, M Meuth. Characterisation of normal and malignant urothelium. 1/10/2001-30/9/2005. £477,928

EPSRC GR/S62321.  R H Smallwood, W M L Holcombe, R J Gaizauskas, D R Hose, J Southgate, R H Clayton, S Mac Neil. The Epitheliome: computational modelling of epithelial tissue. 1/01/2005-31/12/2009. £1,596,474

EPSRC GR/S62338.  J Southgate, R H Smallwood, W M L Holcombe, R J Gaizauskas, D R Hose, R H Clayton, S Mac Neil. The Epitheliome: computational modelling of epithelial tissue. 1/01/2005-31/12/2009. £442,846

BBSRC BBSB04056. E Qwarnstrom, R Smallwood, M Holcombe. Mathematical analysis of regulation of limiting NF-kB activity. 1/10/04-31/09/07. £173,988

BBSRC BB/E002676/1 R Smallwood, K Groom, R Hogg, M Hopkinson, S MacNeil. Development of novel light sources to enable non-invasive imaging of cells in 3D tissue constructs and grafts. 1/11/2006-31/10/2009 £704,287

Commercial contract.  R Smallwood and S Mac Neil. Computational and biological models of skin. 2011-2013. £500,000

EU FP7 Work Package 3. R Smallwood, B Brook. AirPROM - Airway Disease: Predicting Outcomes through Patient Specific Computational Modelling. 2011-2016. €12m total, ~€1m for WP3.