Home| Professor of Molecular Medicine & Diabetes |
| Deputy Director (Research), Blizard Institute of Cell and Molecular Science |
Contact details:
| Tel: | +44 20 7377 7111 |
| Fax: | +44 20 7377 7636 |
| Email: | g.a.hitman@qmul.ac.uk |
| Address: |
Centre for Diabetes, |
Biography
Graham Hitman graduated from University College Hospital Medical College in 1976. Post graduate training included posts at many London teaching Hospitals including early diabetes training from David Pyke and Peter Watkins at Kings College Hospital , a RD Lawrence Research Training fellowship at St Bartholomews Hospital with David Galton and as a Lecturer at the London Hospital attached to Bob Cohen. He was elected a Fellow of the Royal College of Physicians in 1990 and received a MD from the University of London in 1994 for work in molecular genetics of diabetes.
In 1986 he was appointed as a Senior Lecturer in Medicine and Honorary Consultant Physician at the Royal London Hospital . His clinical specialty is in diabetes and in addition to general diabetes work he runs clinics for adolescent patients, cystic fibrosis related diabetes and lipid disorders. In 1995 he was awarded a personal chair in Molecular Medicine and Diabetes. Since 2003 he has been Deputy Director of the Institute of Cell and Molecular Science and was Centre Lead for Diabetes between 2000-2006. Prof Hitman currently leads together with Prof Chris Griffiths, the North East London Diabetes Local Research Network [ http://www.ukdrn.org ]. His research work is currently being funded by the Medical Research Council [National Prevention Research Initiative], Department of Health, Diabetes UK and other charities. He has received a number of prestigious awards and lectures in India , Bangladesh and International Societies; the most recent being made a patron of the Diabetes Association of Bangladesh. This reflects a special interest that Professor Hitman has developed in the aetiology and prevention of diabetes in South Asian populations. He has published over 175 peer reviewed publications many related to the genetics of diabetes and edited one book 'Type 2 diabetes; prediction and prevention.
Research Activity
Over the last 20 or more years his main interests have been the molecular genetics of diabetes & related disorders and the periodic fevers leading to a number of seminal publications.
Current lab based research is focused into 3 areas:
1. Gene Discovery
The last year has been very exiting with discovery of several new diabetes genes of which he was a contributor to the type 2 diabetes component of the the Wellcome Trust Case Consortium Collaboration and DIAGRAM consortium with seminal publications in Nature, Science and Nature Genetics. 2008 will see the results of a Perlegen 600K genome wide association scan of 2500 patients with type 2 diabetes as part of the CARDS study of which the genetic component is led by Prof Hitman and Prof Helen Colohoun ( Dundee ).
2. Epigenetic studies
As more genes are discovered there will be a shift in focus from DNA genotyping to questions of epigenetic modifications, the transcriptome, protein structure/function and protein interactions, developmental and physiological pathways and systems biology as routes to the medical application of this knowledge. More specifically we have initiated with Vardham Rakyan (Lecturer within Centre) epigenetic studies using Nimblegen arrays (directed to the top hits in the genome wide association scans in diabetes) and the use of whole methylome arrays to dissect the gene to environment interaction
3. Functional Genomics and other studies
Best illustrated by work with Mark Turner (Lecturer within centre) on calpain10 which we have demonstrated to be a key molecule in insulin trafficking. We are also elucidating the functional consequences of TNF receptor 1 ( TNFRSF1A ) mutations and their effect on NFkB signaling. Causes of diabetes and cardiovascular disease in South Asians continues to be of great interest with work on the vitamin D axis, the recent elucidation of genetic causes of fibrocalculous pancreatic diabetes and the investigation of the spectrum of diabetes in those between diagnosed under the age of 30 years but that do not have type 1 diabetes.
Clinical Research of direct patient benefit
More recently he has also been additionally involved in more clinically applied research including the feasibility of prevention of diabetes in the Bangladeshi population for which he is the Principal Investigator of a Medical Research Council NPRI pilot trial (http://www.npri.org.uk ) and he is one of several PIs for the Collaborative Atrovastatin Diabetes Study (CARDS http://www.cardstrial.org/ ) that has heavily influenced current guidelines for the routine use of statins in diabetes. He is also a co-investigator of a self management trial for type 2 diabetes funded by Diabetes UK .
Key Publications
• Festenstein,H, Awad,J, Hitman , GA , Cutbush,S, Groves ,AV, Cassell,P, Ollier,W, Sachs,JA: New HLA DNA polymorphisms associated with autoimmune diseases. Nature 322:64-67, 1986
• Hitman,GA , Niven,MJ, Festenstein,H, Cassell,PG, Awad,J, Walker-Smith,J, Leonard,JN, Fry,L, Ciclitira,P, Kumar,P, .: HLA class II alpha chain gene polymorphisms in patients with insulin-dependent diabetes mellitus, dermatitis herpetiformis, and celiac disease. J Clin Invest 79:609-615, 1987
• McDermott,MF, Aksentijevich,I, Galon,J, McDermott,EM, Ogunkolade,BW, Centola,M, Mansfield,E, Gadina,M, Karenko,L, Pettersson,T, McCarthy,J, Frucht,DM, Aringer,M, Torosyan,Y, Teppo,AM, Wilson,M, Karaarslan,HM, Wan,Y, Todd,I, Wood,G, Schlimgen,R, Kumarajeewa,TR, Cooper,SM, Vella,JP, Amos,CI, Mulley,J, Quane,KA, Molloy,MG, Ranki,A, Powell,RJ, Hitman,GA , O'Shea,JJ, Kastner,DL: Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97:133-144, 1999
• Cassell,PG, Jackson,AE, North,BV, Evans,JC, Syndercombe-Court, Phillips,C, Ramachandran,A, Snehalatha,C, Gelding,SV, Vijayaravaghan,S, Curtis,D, Hitman,GA : Haplotype combinations of calpain 10 gene polymorphisms associate with increased risk of impaired glucose tolerance and type 2 diabetes in South Indians. Diabetes 51:1622-1628, 2002
• Hassan,Z, Mohan,V, Ali,L, Allotey,R, Barakat,K, Faruque,MO, Deepa,R, McDermott,MF, Jackson,AE, Cassell,P, Curtis,D, Gelding,SV, Vijayaravaghan,S, Gyr,N, Whitcomb,DC, Khan,AK, Hitman,GA : SPINK1 is a susceptibility gene for fibrocalculous pancreatic diabetes in subjects from the Indian subcontinent. Am J Hum Genet 71:964-968, 2002
• Ogunkolade,BW, Boucher,BJ, Prahl,JM, Bustin,SA, Burrin,JM, Noonan,K, North,BV, Mannan,N, McDermott,MF, DeLuca,HF, Hitman,GA : Vitamin D receptor (VDR) mRNA and VDR protein levels in relation to vitamin D status, insulin secretory capacity, and VDR genotype in Bangladeshi Asians. Diabetes 51:2294-2300, 2002
• Colhoun,HM, Betteridge,DJ, Durrington,PN, Hitman,GA , Neil,HA, Livingstone,SJ, Thomason,MJ, Mackness,MI, Charlton-Menys,V, Fuller,JH: Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 364:685-696, 2004
• Marshall ,C, Hitman , GA , Partridge,CJ, Clark ,A, Ma,H, Shearer,TR, Turner,MD: Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic beta-cells. Mol Endocrinol 19:213-224, 2005
• Zeggini,E, Weedon,MN, Lindgren,CM, Frayling,TM, Elliott,KS, Lango,H, Timpson,NJ, Perry,JR, Rayner,NW, Freathy,RM, Barrett,JC, Shields,B, Morris,AP, Ellard,S, Groves,CJ, Harries,LW, Marchini,JL, Owen,KR, Knight,B, Cardon,LR, Walker,M, Hitman,GA , Morris,AD, Wellcome Case Control Study Consortium, Hattersely, AT, McCarthy MI: Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316:1336-1341, 2007
• Frayling,TM, Timpson,NJ, Weedon,MN, Zeggini,E, Freathy,RM, Lindgren,CM, Perry,JR, Elliott,KS, Lango,H, Rayner,NW, Shields,B, Harries,LW, Barrett,JC, Ellard,S, Groves,CJ, Knight,B, Patch,AM, Ness,AR, Ebrahim,S, Lawlor,DA, Ring,SM, Ben-Shlomo,Y, Jarvelin,MR, Sovio,U, Bennett,AJ, Melzer,D, Ferrucci,L, Loos,RJ, Barroso,I, Wareham,NJ, Karpe,F, Owen,KR, Cardon,LR, Walker,M, Hitman,GA , Palmer,CN, Doney,AS, Morris,AD, Smith,GD, Hattersley,AT, McCarthy,MI: A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889-894, 2007
