HomeGroup Lead
Autoimmune Thrombocytopenia and Dendritic Cell Biology
Lead
Prof Adrian C Newland MA, FRCP(UK), FRCPath - Unit Lead, Academic Haematology Unit
Dr Samir Agrawal BSc, MBChB, PhD, MRCP, MRCPath
Dr Drew Provan BSc MBChB MD FRCP FRCPath
Prof Marion Macey
Research field
This group with an international reputation in ATP research has developed an international registry and collaborative research effort. Currently the genetics of this autoimmune disorder is being investigated with some emphasis on the role of the dendritic cell. These research lines are linked with the second main theme of lymphoproliferative disease, looking at the relationship of apoptosis to autoimmune disease. Li Jia is exploring the pathways of apoptosis and their manipulation by gene transfection and the impact of small molecules.
Key research papers
1 Johansson U, Lawson C, Dabare M, Syndercombe-Court D, Newland AC, Howells GL, Macey MG (2005). Human peripheral blood monocytes express protease receptor-2 and respond to receptor activation by production of IL-6, IL-8, and IL-1{beta} J Leukoc Biol. [Epub ahead of print]
2 Johansson U, Macey MG, Kenny D, Provan AB, Newland AC (2005). The role of natural killer T (NKT) cells in immune thrombocytopenia: is strong in vitro NKT cell activity related to the development of remission? Br J Haematol. 129(4):564-5.
3 Fu, W.N., Bertoni, F., Kelsey, S.M., McElwaine, S.M., Cotter, F.E., Newland, A.C. & Jia, L. (2003) Role of DNA methylation in the suppression of Apaf-1 protein in human leukaemia. Oncogene, 22, 451-455.
4 Jia, L., Patwari, Y., Kelsey, S.M., Srinivasula, S.M., Agrawal, S.G., Alnemri, E.S. & Newland, A.C. (2003). Role of Smac in human leukaemic cell apoptosis and proliferation. Oncogene, 22, 1589-1599.
Dr Denise Syndercombe-Court C Biol, MIBiol, CSci, FIBMS, DMedT, PhD
Research field
Denise Syndercombe Court is the sole UK representative in the European DNA Profiling research group and a current holder of an EU grant looking at the future of SNP typing in forensic identification. The group's current research utilises SNPs and STRs to investigate ethnic population differences in autosomal, X and Y chromosome and MtDNA, in order to provide population models for intelligence purposes. Innovative models in artificial SNP production are also being used to develop tools for unknown mixture analysis. The group are also developing population defining multiplexes in order to reliably predict ethnicity from trace material, such as might be left by touch on items at a scene. Although there is a perceived current need for ethnicity definition stimulated by anti-terrorist concerns, the group sees its future role in being able to use genetic markers in order to be able to build up a picture of an individual's physical traits to aid intelligence. The ability to investigate developed markers in such low volumes requires access to high sensitivity methodology and instrumentation.
Key research papers
1 Ballard DJ, Phillips C, Thacker CR, Robson C, Revoir AP, Syndercombe-Court D (2005). Epub 2004 Dec 9. Y chromosome STR haplotypes in three UK populations. Forensic Sci Int. 152:289-305.
2 Parson W, Brandstatter A, Alonso A, Brandt N, Brinkmann B, Carracedo A, Corach D, Froment O, Furac I, Grzybowski T, Hedberg K, Keyser-Tracqui C, Kupiec T, Lutz-Bonengel S, Mevag B, Ploski R, Schmitter H, Schneider P, Syndercombe-Court D, Sorensen E, Thew H, Tully G, Scheithauer R (2004). The EDNAP mitochondrial DNA population database (EMPOP) collaborative exercises: organisation, results and perspectives. Forensic Sci Int.139:215-26.
3 Brion M, Dupuy BM, Heinrich M, Hohoff C, Hoste B, Ludes B, Mevag B, Morling N, Niederstatter H, Parson W, Sanchez J, Bender K, Siebert N, Thacker C, Vide C, Carracedo A (2005). A collaborative study of the EDNAP group regarding Y-chromosome binary polymorphism analysis. Forensic Sci Int.153:103-108.
4 María Brión, Alejandro Blanco-Verea, Angel Carracedo, Kinga Balogh, Beate Stradmann-Bellinghausen, Magdalena Bogus, Peter M. Schneider, Juan J. Sanchez, Claus Børsting, Niels Morling, Catherine Thacker, Denise Syndercombe-Court. Study of the specific geographical distribution of male lineages by the use of a "Major Y-chromosome haplogroup typing kit" Electrophoresis, In Press.
5 D.J. Ballard, , C. Phillips, G. Wright, C.R. Thacker, C. Robson, A.P. Revoir and D. Syndercombe Court. A study of mutation rates and the characterisation of intermediate, null and duplicated alleles for 13 Y chromosome STRs. Forensic Science International, In Press.
Prof John Pasi MB ChB PhD FRCP FRCPath FRCPCH
Research field
Research interests lie in gene therapy for haemophilia, molecular pathology of von Willebrands disease, the link between cancer and thrombosis and the mechanisms of inhibitor development in haemophilia A. A gene therapy trial for using adeno- associated virus for the transfer of factor IX for haemophilia B has recently been approved in conjunction with colleagues at University College London .
Key research papers
1 Jenkins PV, Pasi KJ , Perkins SJ. Molecular modelling of ligand and mutation sites of the Type A domains of human von Willebrand factor and their relevance to von Willebrand's disease Blood 1998: 91: 2032-2044
2 Fields PA, Kowalczyk DW, Arruda VA , Armstrong E, McClelland M, Hagstrom J, Pasi KJ , Ertl HG, Herzog R, High KA Role of vector in activation of T cell subsets in immune response against secreted transgene product factor IX Molecular Therapy 2000:1: 225-235
3 Roth DA, Kessler CM, Pasi KJ , Rup B, Courter SG, Tubridy K for the Recombinant Factor IX Study Group Human Recombinant Factor IX: Safety and Efficacy Studies in Patients With Hemophilia B Blood 2001: 98: 3600-3606
4 Bayele HK, Murdock PJ, Perry DJ, Pasi KJ Simple shifts in redox/thiol balance that perturb blood coagulation FEBS Letters 2002: 510: 67-70
5 Behrman M, Pasi J , Saint-Remy J-M, Kotitischke R, Kloft M. VWF modulates FVIII immunogenicity: comparative study of different plasma-derived and recombinant FVIII concentrates in a hemophilia A mouse model. Thrombosis and Haemostasis 2002: 88: 221-229
6 Bowen DJ, Collins PW, Lester W, Cumming AM , Keeney SM, Grundy P, Enayat SM, Bolton-Maggs PHB, Keeling DM, Khair K, Tait RC, Wilde JT, Pasi KJ , Hill FGH, on behalf of UK Haemophilia Centre Doctors' Organization. The prevalence of the cysteine1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease: co-segregation with increased susceptibility to AD AM TS13 proteolysis but not clinical phenotype. British Journal of Haematology, 2005: 128: 830-836
7 Eikenboom J, Van Marion V, Putter H, Goodeve A, Rodeghiero F, Castaman G, Federici AB, Batlle J, Meyer D, Mazurier C, Goudemand J, Schneppenheim R, Budde U, Ingerslev J, Vorlova Z, Habart D, Holmberg L, Lethagen S, Pasi J , Hill F, Peake I. Linkage analysis in families diagnosed with type 1 von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 VWD. Journal of Thrombosis and Haemostasis 2006: 4: 774-782
8 Cumming A, Grundy P, Keeney S, Lester W, Enayat S, Guilliatt A, Bowen D, Pasi J , Keeling D, Hill F, Bolton-Maggs PH, Hay C, Collins P, the UK Haemophilia Centre Doctors' Organisation. An investigation of the von Willebrand factor genotype in UK patients diagnosed to have type 1 von Willebrand disease. Thrombosis & Haemostasis. 2006: 96:630-41
9 Tosetto A, Rodeghiero F, Castaman G, Bernardi M, Bertoncello K, Goodeve A, Federici AB, Batlle J, Meyer D, Mazurier C, Goudemand J, Eikenboom J, Schneppenheim R, Budde U, Ingerslev J, Vorlova Z, Habart D, Holmberg L, Lethagen S, Pasi J , Hill F, Peake I. Impact of plasma von Willebrand factor levels in the diagnosis of type 1 von Willebrand disease. Journal of Thrombosis and Haemostasis 2007: 5: 715-21
10 Goodeve A, Eikenboom J, Castaman G, Rodeghiero F, Federici AB, Batlle J, Meyer D, Mazurier C, Goudemand J, Schneppenheim R, Budde U, Ingerslev J, Habart D, Vorlova Z, Holmberg L, Lethagen S, Pasi J , Hill F, Hashemi M, Baronciani L, Lambert F, Hallden C, Guilliatt A, Peake I. Phenotype and Genotype of a Cohort of Families Diagnosed with Type 1 von Willebrand Disease in the European Study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD). Blood 2007: 109: 112-121
Dr Paul Telfer MA DM BM BCh FRCP FRCPath
Research field
Natural history, determinants of disease severity, and clinical trials of new therapies in haemoglobin disorders, particularly sickle cell disease and thalassaemia.
Key research papers
1 Telfer PT, Prestcott E, Holden S, Walker M, Hoffbrand AV, Wonke B. Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. British Journal of Haematology . 2000; 110: 971-7
2 Telfer PT, De La Salle B. Antenatal haemoglobinopathy screening. British Journal of Haematology 2000; 110: 1003-4
3 S. Chakravorty, K. Newell, J. Ramchandani, A. Quereshi , R. Ibrahim, B. Datta, P.T. Telfer. Sickle cell disease pain in London and the Caribbean . Archives of Diseases in Childhood 2004; 89: 272-3
4 Rees DC, Olujohungbe AD, Parker NE, Stephens AD, Telfer P, Wright J. Guidelines for the management of the acute painful crisis in sickle cell disease . British Journal of Haematology 2003 123, 744-752.
5 Elander J, Lusher J, Bevan D, Telfer P, Burton B. Understanding the causes of problematic pain management in sickle cell disease: evdence that pseudoaddiction plays a more important role than genuine analgesic dependence. Journal of pain symptom management 2004; 27: 156-169
6 Baldeweg T, Hogan A, Saunders D, Telfer P, Gadian D, Vargha-Khadem F, Kirkham F. White matter injury in children with sickle cell disease detected using voxel-based morphometry. Annals of Neurology, Ann Neurol. 2006 Apr;59(4):662-72 .
7 Hogan A, Prengler M, Kirkham F, Telfer P, Lane R, Vargha-Khadem F, de Haan M. An exploratory study of physiological correlates of neurodevelopmental delay in infants with sickle cell anemia. British Journal of Haematology. Br J Haematol. 2006 Jan;132(1):99-107.
8 Telfer P , Constantinidou G , Andreou P , Christou S , Modell B , Angastiniotis M . Quality of life in thalassemia. Ann N Y Acad Sci. 2005 Nov;1054:273-82.
9 Analgesic Addiction and Pseudoaddiction in Painful Chronic Illness Joanne Lusher , James Elander, David Bevan, Paul Telfer, Bernice Burton. Clin J Pain 2006;22:316-324
10 Survival of medically treated thalassaemia patients in Cyprus . Trends and risk factors over the period 1980-2004. Paul Telfer, Pietro G Coen, Soteroula Christou, Michael Hadjigavriel, Anita Kolnakou, Evangelia Pangalou, Nicos Pavlides, Michael Psiloines, Krikor Simamonian, Georghios Skordos, Maria Sitarou , and Michael Angastiniotis . . Haematologica. 2006 Sep;91(9):1187-92
Lead
Professor Jo Martin MA (Cantab), MB, BS, PhD FRCPath
Academic staff
Dr Cathy Baker
Research field
The neuropathology unit studies a range of disorders including motoneuron disease and examines the genetic basis of these disorders, mechanisms of cell death and mechanisms of neuroprotection. Current studies include the role of dynein in neurodegeneration, and the mechanisms by which inclusion bodies develop. Key achievements by the unit include the linkage of axonal transport defects to motor neuron loss in dynein mutations, and the identification of a novel method of drug delivery into neurons.
Key research papers
1 Guy J, Hendrich B, Holmes M, Martin JE, Bird A (2001) A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 27: 322-326.
2 Hafezparast M, Klocke R, Ruhrberg C, Marquardt A, Ahmad-Annuar A, Bowen S, Lalli G, Witherden AS, Hummerich H, Nicholson S, Morgan PJ, Oozageer R, Priestley JV, Averill S, King VR, Ball S, Peters J, Toda T, Yamamoto A, Hiraoka Y, Augustin M, Korthaus D, Wattler S, Wabnitz P, Dickneite C, Lampel S, Boehme F, Peraus G, Popp A, Rudelius M, Schlegel J, Fuchs H, de Angelis MH, Schiavo G, Shima DT, Russ AP, Stumm G, Martin JE, Fisher EM (2003) Mutations in dynein link motor neuron degeneration to defects in retrograde transport. Science 300: 808-812.