Newcastle University

Research Interests

Major interests in the development of gene therapy and beta cell replacement for diabetes including stem cell approaches; pancreatic/islet transplantation; and pump therapy by continuous subcutaneous insulin infusion.

Esteem Indicators

Committed to career as clinical academic from the outset, undertaking 3 years pre-clinical training towards BSc and a further intercalated honours degree in biochemistry prior to 3 years clinical training leading to MB ChB.

As a specialist clinical trainee in diabetes and endocrinology, I attained an MRC Clinical Training Fellowship and undertook a PhD in molecular and cell biology in the field of gene therapy and beta cell replacement for diabetes with Prof Kevin Docherty.

Having completed specialist training, I attained a prestigious 6 year GlaxoSmithKline Senior Clinical Fellowship enabling me to establish my basic research group and translational research programme in Newcastle.

Having accrued preliminary data, as chair of the UK Islet Transplant Consortium, I led the successful bid for NHS funding of clinical islet transplantation in the UK as a sustainable hub-and-spoke programme.

I am PI on a Diabetes UK-funded grant enabling a detailed experimental approach to detrerimne biomedical and psychosocial outcomes of islet transplantation.

I am PI on a REgeNer8 funded grant to further optimise islet quality assurance and transport with the specific goal of developing in vitro predictors of graft function and immunogenicty correlating with clinical outcomes.

I am PI on an investigator-led multicentre RCT to determine optimised conventional management for those with type 1 diabetes complicated by recurent severe hypoglycaemia.

I was promoted to a personal chair at Newcastle University last year. I am clinical lead for the International Centre for Life Cell Transplant GMP Facility and chair the North East Stem Cell Institute Clinical Translational Group.

I am co-editor with Prof James Shapiro, University of Alberta of the textbook 'Islet transplantation and beta-cell replacement therapy for diabetes'.

Funding

01.02.10-31.01.11 RegeNer8 Translational Regenerative Medicine Award (£299,968)
A sustainable quality-assured system for assessment of pancreatic islets for product release and transport to geographically distant clinical transplant centres

01.01.01.10 -31.12.10 Newcastle Healthcare Charity (Collin M, Hambleton S, Dickinson AM, van Laar J, Shaw JAM) Implementation of mesenchymal stromal cell therapy in Newcastle

01.10.09-30.09.12 Diabetes UK PhD Studentship
Isolation, characterisation and beta-cell differentiation potential of pluripotent stem cells derived from adult human pancreas

01.06.09 Diabetes UK Equipment grant (Arden C; Shaw J; Aldibbiat A £45,000)
Live-cell imaging of protein interactions and lineage tracing of human pancreatic cells

01.05.09-30.04.12 Tolerx Defend1 RCT: anti-CD3 in newly diagnosed Type 1 diabetes (Leech N, Shaw J, Walker M)

01.10.08-31.07.12 Diabetes UK (£1,401,716)
Prevention of recurrent severe hypoglycaemia: a definitive RCT comparing optimised MDI and CSII with or without adjunctive real-time continuous glucose monitoring

01.04.08-31.03.11 Diabetes UK project grant (Walker M, Chinnery P, Shaw J £155,359 )
Does decreased mitochondrial DNA copy number with ageing impair pancreatic beta-cell function?

01.03.08 Medtronic (Shaw local PI)
Evaluation of first clinically available pump with ‘closed loop’ capability

01.01.08-31.12.13 Diabetes UK (Agius L, Arden C, Shaw J £29,239)
Equipment for insulin determination by HTRF

01.12.07-31.05.08 North East Stem Cell Institute (£8,000)
Phenotypic characterisation of stem cell derived beta-cells prior to clinical translation

01.10.07-30.09.12 Sanofi-Aventis (Shaw local PI £15,000)
Cardiovascular Risk Evaluation in people with type 2 Diabetes on Insulin Therapy. Long-term international non- interventional study in people with Type 2 diabetes treated with insulin.

01.07.07-31.01.12 Diabetes UK project grant (£430,255)
Establishment of optimised biomedical and psychosocial measures to determine overall outcomes in islet transplant recipients

01.01.07 -30.06.07 Diabetes Research and Wellness Foundation project grant (£29,940)
Enhancement of â-cell mass and function in human islets by physiological factors upregulated in pregnancy

01.01.07-31.12.07 Diabetes Foundation project grant (Amiel SA; Shaw JAM £160,000)
A proposal to validate and establish remote islet isolation for the treatment of Type 1 diabetes in the UK

1.8.00-31.7.06 Glaxo-Wellcome Senior Fellowship: (£350,000)
Transplantation and gene therapy for diabetes

01.06.05-31.05.06 Newcastle upon Tyne Hospitals NHS Charity research grant (£38,423)
Remote islet transplantation: a feasibility study

01.04.05 One North East stem cell equipment grant (£27,000)

01.01.05-31.12.06 Blood glucose awareness training in Type 1 diabetes
Principal investigator initiated (supported by Novo Nordisk £25,000)

01.10.04-30.09.05 Diabetes UK Project Grant (Agius L; Shaw J £45,056)
Cellular analysis of glucokinase MODY mutants in pancreatic beta-cells and hepatocytes

1.6.02-30.9.04 Project grant supported by Aventis / MiniMed (£160,000)
Can hypoglycaemia awareness be restored in individuals with established Type 1 diabetes mellitus and severe hypoglycaemia by detection and targeted prevention of hypoglycaemia employing an optimised subcutaneous insulin regime employing insulin Glargine

1.11.01-31.10.02 Freeman Hospital Trustees Grant (£37567):
Development of glucose-responsive insulin secretion in transfected human myoblasts

1.11.01 Joint Research Equipment Initiative (MRC) grant (Agius L / Shaw JAM £27329)

• Barlow AD, Xie J, Moore CE, Campbell SC, Shaw JA, Nicholson ML, Herbert TP. Rapamycin toxicity in MIN6 cells and rat and human islets is mediated by the inhibition of mTOR complex 2 (mTORC2). Diabetologia 2012, 55(5), 1355-1365.
• Choudhary P, Shin J, Wang YY, Evans ML, Hammond PJ, Kerr D, Shaw JAM, Pickup JC, Amiel SA. Insulin Pump Therapy With Automated Insulin Suspension in Response to Hypoglycemia Reduction in nocturnal hypoglycemia in those at greatest risk. Diabetes Care 2011, 34(9), 2023-2025.
• White M, Al-Turaifi H, Holliman G, Aldibbiat A, Mahmoud A, Shaw JAM. Pluripotency-associated stem cell marker expression in proliferative cell cultures derived from adult human pancreas. Journal of Endocrinology 2011, 211(2), 169-176.
• Wallace K, Shaw J, White SA, Wright S, Burt AD, Wright MC. Prolonged glucocorticoid exposure results in the appearance of hepatocytes in the adult pancreas. In: Journal of Hepatology: 46th Annual Meeting of the European Association for the Study of the Liver (EASL). 2011, Berlin, Germany: Elsevier BV.
• Hammond P, Amiel S, Dayan C, Kerr D, Pickup J, Shaw J, Campbell F, Greene S, Hindmarsh P. ABCD position statement on continuous glucose monitoring: Use of glucose sensing in outpatient clinical diabetes care. Practical Diabetes International 2010, 27(2), 66-68.
• Abdul Shakoor SK, Aldibbiat A, Ingoe LE, Campbell SC, Sibal L, Shaw J, Home PD, Razvi S, Weaver JU. Endothelial Progenitor Cells in Subclinical Hypothyroidism: The Effect of Thyroid Hormone Replacement Therapy. Journal of Clinical Endocrinology and Metabolism 2010, 95(1), 319-322.
• Wallace K, White SA, Shaw JA, Burt AD, Wright MC. Chronic Elevated Systemic Glucocorticocoid Results in Widespread Pancreatic-Hepatic Trans-Differentiation In Vivo. In: The Liver Meeting 2009: 60th Annual Meeting of the American Association for the Study of Liver Diseases. 2009, Boston, Massachusetts: Hepatology: John Wiley & Sons, Inc..
• Sibal L, Aldibbiat A, Agarwal SC, Mitchell G, Oates C, Razvi S, Weaver JU, Shaw JA, Home PD. Circulating endothelial progenitor cells, endothelial function, carotid intima-media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria. Diabetologia 2009, 52(8), 1464-1473.
• Reddy MS, Kibondo A, Aldibbiat A, Stamp S, Shenton B, Shaw JAM, Carter N, Cunningham A, Talbot D. Improved Preservation of Non Heart-Beating- Donor Pancreases Prior to Islet Isolation Using Portal Venous Oxygen Persufflation.. American Journal of Transplantation 2009, 9, 405.
• Niessen S, Mahmoud A, Arden C, Brown A, Campbell S, Aldibbiat A, Church D, Shaw J. Muscle targeted gene therapy for diabetes mellitus: role of proteasomal decay in mutant proinsulin plasmid efficiency. In: Human Gene and Cell Therapy: 17th European Society of Gene and Cell Therapy.2009,Hannover, Germany:Mary Ann Liebert, Inc. Publishers
• Mahmoud A, Niessen S, Aldibbiat A, Al-Turaifi H, Huggins C , Shaw JAM. Muscle-targeted gene transfer enables continuous secretion of GLP-1 and exendin-4 in mice. Human Gene Therapy 2009, 20(11), 1542.
• White S, Shaw J, Sutherland D. Pancreas transplantation. The Lancet 2009. ,373 9677 1808-1817.
• Reddy M, Kibondo A, Aldibbiat A, Stamp S, Shenton BK, Shaw JAM, Carter N, Cunningham A, Talbot D. Portal venous oxygen persufflation for the preservation of non heart-beating-donor pancreases prior to islet isolation. In: 14th Congress of the European Society for Organ Transplantation. 2009, Paris, France: Transplant International: Wiley-Blackwell.
• Arden C, Hampson L, Huang G, Shaw J, Aldibbiat A, Holliman G, Manas D, Khan S, Lange A, Agius L. A role for PFK-2/FBPase-2, as distinct from fructose 2,6-bisphosphate, in regulation of insulin secretion in pancreatic β-cells. Biochemical Journal 2008, 411(1), 41-51.
• Niessen S, Mahmoud A, Aldibbiat A, Campbell S, Brown A, Huggins C, Catchpole B, Church D, Shaw J. Development of muscle targeted gene therapy with a mutant canine proinsulin plasmid for the treatment of canine diabetes mellitus. In: 16th Annual Congress of the European Society of Gene and Cell Therapy. 2008, Brugge, Belgium: Human Gene Theraphy: Mary Ann Liebert Inc..
• AlTuraifi HRH, Aldibbiat AIM, Holliman GN, Campbell SC, Shaw JAM, Huang GGC, Amiel SGC. Expression of pluripotent stem cell markers within intact adult human pancreas and proliferative adherent cell cultures derived from digested pancreas. Diabetologia 2008, 51(s1), S182 no. 437.
• Mahmoud A, Aldibbiat A, Niessen SJM, Campbell SC, Holliman GN, Joshi S, Scougall KT, Shaw JAM. Expression, storage and rapid regulated secretion of active glucagon like peptide-1 following muscle-targeted gene transfer. Diabetologia 2008, 51(s1), S363 no. 906.
• Aldibbiat A, Holliman GN, Al-Turaifi H, Campbell SC, Huang G, Shaw J. Generation of insulin-synthesising pseudo-islets from adult stem cell cultures derived from the human pancreas. Diabetologia 2008, 51(Supplement 1), S183 no. 439.
• Aldibbiat A, Marriott CE, Scougall KT, Campbell SC, Huang GC, Macfarlane WM, Shaw JAM. Inability to process and store proinsulin in transdifferentiated pancreatic acinar cells lacking the regulated secretory pathway. Journal of Endocrinology 2008, 196(1), 33-43.
• Niessen SJM, Mahmoud A, Aldibbiat A, Huggins C, Church DB, Shaw JAM. Muscle-targeted gene therapy for the treatment of diabetes mellitus: Investigating the role of the immune system when employing mutant (pro)insulin. Diabetologia 2008, 51(Supplement 1), S243 no. 600.
• Niessen S, Mahmoud A, Campbell S, Brown A, Aldibbiat A, Huggins C, Church D, Shaw J. Novel furin-cleavable human insulin construct (hppI5) for muscle targeted gene therapy in diabetes mellitus. In: 16th Annual Congress of the European Society of Gene and Cell Therapy. 2008, Brugge, Belgium: Human Gene Therapy: Mary Ann Liebert Inc..
• Campbell SC, Aldibbiat A, Marriott CE, Landy C, Ali T, Ferris WF, Butler CS, Shaw JA, Macfarlane WM. Selenium stimulates pancreatic beta-cell gene expression and enhances islet function. FEBS Letters 2008, 582(15), 2333-2337.
• Sibal L, Jones A, Aldibbiat A, Mitchell G, Oates C, Weaver J, Shaw JAM, Home PD. The influence of the presence of retinopathy on the circulating endothelial progenitor cell counts, endothelial function and carotid intima-media thickness in type I diabetes. Diabetologia 2008, 51(Supplement 1), S552 no. 1372.
• Thomas RM, Aldibbiat A, Griffin W, Cox MAA, Leech NJ, Shaw JAM. A randomized pilot study in type 1 diabetes complicated by severe hypoglycaemia, comparing rigorous hypoglycaemia avoidance with insulin analogue therapy, CSII or education alone. Diabetic Medicine 2007, 24(7), 778-783.
• Arden C, Trainer A, De La Iglesia N, Scougall KT, Gloyn AL, Lange AJ, Shaw J, Matschinsky FM, Agius L. Cell biology assessment of glucokinase mutations V62M and G72R in pancreatic β-cells: Evidence for cellular instability of catalytic activity. Diabetes 2007, 56(7), 1773-1782.
• Ratanamart J, Huggins CG, Kirby JA, Shaw J. In vitro and in vivo evaluation of intrinsic immunogenicity of reporter and insulin gene therapy plasmids. Journal of Gene Medicine 2007, 9(8), 703-714.
• Aldibbiat A, Huang GC, Zhao M, Reddy MS, Holliman GH, Dunn J, Dickinson AM, Manas DM, Amiel SA, Shaw JAM. [abstract] Confirmation of maintained sterility, viability and function in clinical-grade human islets following transport from an approved geographically-distance isolation facility. Diabetic Medicine 2006,23 s2 23 abstract no. A86.
• Arden C, Scougall KT, Shaw JAM, Agius L. [abstract] Generation of MIN6 stable cell lines expressing GFP-tagged glucokinase for cellular analysis of glucokinase mutants. Diabetic Medicine 2006,23 s2 9 abstract no. A30.
• Sibal L, Aldibbiat A, Harvey IJ, Shenton BK, Holliman GN, Shaw JAM, Home PD. [abstract] Identification and quantification of circulating endothelial progenitor cells in individuals with Type 1 diabetes and non-diabetic controls. Diabetic Medicine 2006,23 s2 49 abstract no. P74.
• Arutchelvam V, Heslop E, Welsh P, Griffins W, Weatherburn S, Aldibbiat A, Leech N, Shaw JAM. [abstract] Safety and efficacy of continuous subcutaneous insulin infusion therapy in relation to pre-intervention HbA1c. Diabetic Medicine 2006,23 s2 86 abstract no. P222.
• Ratanamart J, Shaw JAM. Plasmid-mediated muscle-targeted gene therapy for circulating therapeutic protein replacement: A tale of the tortoise and the hare?. Current Gene Therapy 2006. , 6(1), 93-110.
• Wilson MO, Scougall KT, McIntyre EA, Shaw JAM. Storage, processing and rapid regulated secretion of insulin following gene transfer to human muscle. In: British Society for Gene Therapy: 2nd Annual Meeting.2006,Manchester, UK
• Wong YT, Del-Rio-Martin J, Jaques B, Shaw JAM, Talbot D. Audit of diabetes in a renal transplant population. In: Transplantation Proceedings. 2005, Elsevier.
• Aldibbiat A, Scougall KT, Campbell SC, Macfarlane WM, Shaw JAM. Proinsulin overexpression as a tool for characterization of β-cell phenotype in transdifferentiation studies. Diabetes 2005,under review .
• Ratanamart J, Huggins CG, Shaw JAM. Tetracycline-regulated human proinsulin secretion following plasmid-mediated gene transfer to muscle. In: British Society for Gene Therapy: 2nd Annual Meeting.2005,Manchester, UK
• Wilson MO, Scougall KT, Ratanamart J, McIntyre EA, Shaw JAM. Tetracycline-regulated secretion of human (pro)insulin following plasmid-mediated transfection of human muscle. Journal of Molecular Endocrinology 2005, 34(2), 391-403.
• Aldibbiat K, Scougall KT, Campbell SC, Macfarlane WM, Shaw J. Characterisation of pancreatic acinar cells for endocrine potential and determination of proinsulin processing and secretion following transfection with a human preproinsulin gene. In: Journal of Gene Medicine: 1st Annual Conference of the British Society for Gene Therapy. 2004, Oxford, UK: John Wiley & Sons, Inc..
• Ratanamart J, Scougall KT, Kirby JA, Shaw JAM. Establishment of an in vitro bioassay for immunogenicity of bacterial lipopolysaccharide and unmethylated CpG motifs in plasmid-derived gene therapy vectors. In: Journal of Gene Medicine: 1st Annual Conference of the British Society for Gene Therapy. 2004, Oxford, UK: John Wiley & Sons, Inc..
• Campbell RN, Shaw JAM, Macfarlane WM. Generation of glucose-responsive insulin expression constructs for use in a muscle-targeted gene therapy approach to the treatment of diabetes mellitus. In: Journal of Gene Medicine: 1st Annual Conference of the British Society for Gene Therapy. 2004, Oxford, UK: John Wiley & Sons, Inc..
• Wilson MO, Scougall KT, McIntyre E, Yeaman SJ, Walker M, Shaw JAM. Towards muscle-targeted gene therapy for diabetes: Tetracycline-repressible transcriptional regulation of (pro)insulin secretion in human muscle. In: 1st Annual Conference of the British Society for Gene Therapy.2004,Keble College, Oxford:Journal of Gene Medicine: John Wiley & Sons Ltd
• Wilson MO, McIntyre EA, Scougall KT, Shearing PA, Walker M, Yeaman SJ, Shaw JAM. Tetracycline-regulated (pro)insulin secretion and processing to mature insulin following plasmid-mediated transfection of human muscle. Diabetic Medicine 2003, 20(s2), 9.
• Scougall KT, Maltin CA, Shaw JAM. Tetracycline-regulated secretion of human insulin in a transfected non-endocrine cell line. Journal of Molecular Endocrinology 2003,30 3 331-346.
• Scougall KT, Shaw JAM. Tetracycline-regulated secretion of human insulin in transfected primary myoblasts. Biochemical and Biophysical Research Communications 2003, 304(1), 167-175.
• Shaw JAM, Pearson DWM, Krukowski ZH, Fisher PM, Bevan JS. Cushing's syndrome during pregnancy: Curative Adrenalectomy at 31 Weeks Gestation. European Journal of Obstetrics & Gynecology and Reproductive Biology 2002, 105(2), 189-191.
• Shaw JAM. Development of alternatives to insulin injection by genetic engineering. Diabetes Voice 2002, 47, 30-34.
• Shaw JAM, Docherty K. Genetic engineering in the treatment of diabetes. In: Wass, J.A.H., Shalet, S.M, ed. Oxford Textbook of Endocrinology and Diabetes. Oxford: Oxford University Press, 2002, pp.1866-1872.
• Unwin N, Shaw J, Zimmet P, Alberti KGMM. Impaired glucose tolerance and impaired fasting glycaemia: the current status on definition and intervention. Diabetic Medicine 2002, 19(9), 708-723.
• Thomas RM, Korim MT, Kerrison M, Leech N, Shaw JAM. Retrospective audit of individuals with Type 1 diabetes mellitus with and without altered hypoglycaemia awareness / severe hypoglycaemia attending Newcastle Diabetes Centre. In: Endocrine Abstracts: 193rd Meeting of the Society for Endocrinology. 2002, London: BioScientifica Ltd.
• Shaw JAM, Delday MI, Hart AW, Docherty HM, Maltin CA, Docherty K. Secretion of bioactive human insulin following plasm id-mediated gene transfer to non-neuroendocrine cell lines, primary cultures and rat skeletal muscle in vivo. European Journal of Endocrinology 2002, 172(3), 653-672.
• Zimmet P, Alberti KGMM, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001, 414(6865), 782-787.
• Scougall KT, Shaw JAM. Tetracycline-regulated secretion of mature human insulin in transfected primary rat myoblasts. In: 37th Annual Meeting of the EASD. 2001, Glasgow, UK: Springer.
• Abraham P, Sati H, Kumar N, Shaw JAM, Middleton M, Culligan D, Watson H, Murray A, Bevan JS. Hyperprolactinaemia is uncommon in patients with Hodgkin’s and non-Hodgkin’s lymphoma. Journal of Endocrinology 2000, 164 Suppl, P35.
• Scougall KT, Maltin CA, Shaw JAM. Tetracycline-regulated secretion of human pro/insulin in transfected primary rat. Diab Res Clin Pract 2000, 50 (Suppl 1), S180.
• Scougall KT, Shaw JAM. Tetracycline-responsive secretion of human proinsulin in transfected fibroblasts. Diabetic Medicine 2000, 17(3) Suppl 1, 4.
• Shaw JAM, Delday MI, Scougall KT, Hart A, Maltin CA, Docherty K. Constitutive secretion of human insulin in growing and mature rats following intramuscular injection of naked plasmid DNA. Journal of Endocrinology 1999, 163 Suppl, OC28.
• Shaw JAM and Docherty KD. Gene Therapy for NIDDM - will it have a role?. Towards Prediction and Prevention of NIDDM 1999.
• Shaw JAM, Delday MI, Hart A, Docherty HM, Maltin CA, Docherty K. Towards off the shelf gene therapy for diabetes: insulin expression in rats following intramuscular DNA injection. Diabetic Medicine 1999, 16(5) Suppl1, 28.