Professor Tom Vulliamy combines research into genetic diseases with teaching and training of students and doctors. The main focus of his research is the identification of disease genes that cause bone marrow failure. Positional cloning projects involving families with dyskeratosis congenita have shown that molecules involved in telomere maintenance are defective in this disease. Functional characterisation of these mutations describes how defective telomeres result in a premature aging phenotype in humans. The work has been translated into molecular diagnosis for at risk individuals. Next generation sequencing strategies are currently being employed in further gene discovery projects.
He is also involved in a pharmacogenetic study, investigating the role of a genetic polymorphism in the efficacy of a drug used to treat preschool wheeze. Specifically, a randomised placebo controlled trial of the intermittent use montelukast is being stratified according to a genotype (ALOX5) that influences how children respond to this leukotriene antagonist.
Additional interests include the molecular basis of glucose-6 phosphate dehydrogenase deficiency, one of the most common human genetic disorders due to the resistance it confers during malaria infection. This work has lead to an ongoing study of the genetic factors that influence disease severity in a large cohort of sickle cell disease patients being carried out as a collaborative study between London, Paris and Cotonou in West Africa.
Tom Vulliamy obtained a Zoology degree at Oxford University and a PhD working with Martin Raff at UCL. Since then has worked in human genetics, initially with Jim Gusella at Harvard Medical School and then with Lucio Luzzatto at the Hammersmith Hospital in London. He worked as a Clinical Scientist running a small molecular diagnostic laboratory while collaborating with Inderjeet Dokal and Philip Mason in the cloning of disease genes. He was appointed Senior Lecturer at Barts and The London SMD in 2006 and promoted to Professor in 2015.
Telomere biology; bone marrow failure; identification of disease genes; sickle cell disease; glucose-6-phosphate dehydrogenase deficiency
Recent and ongoing research projects:
The genetic basis and pathophysiology of dyskeratosis congenita, aplastic anaemia, myelodysplasia and related disorders.
Parent-determined oral montelukast therapy for preschool wheeze with stratification for arachidonate-5-lipoxygenase promoter genotype.
Natural History of Sickle Cell Disease in Cotonou (The Republic of Benin): Influence of Genetic and Environmental Factors on the Clinical Expression of the Disease
Tummala H, Walne A J, Williams M, Bockett N, Collopy L, Cardoso S, Ellison A, Wynn R, Leblanc T, Fitzgibbon J, Kelsell D P, van Heel D A, Payne E, Plagnol V, Dokal I and Vulliamy T (2016) DNAJC21 mutations link a cancer prone bone marrow failure syndrome to corrupted 60S ribosome subunit maturation. Am J Hum Genet, 99: 115-124
Tummala H, Walne AJ, Collopy LC, Cardoso SR, de la Fuente J, Lawson S, Powell J, Cooper N, Foster A, Mohammed S, Plagnol V, Vulliamy T, Dokal I (2015) Poly(A)-specific ribonuclease deficiency impacts on telomere biology causing dyskeratosis congenita. J Clin Invest, 125:2151-2160. Video link:
Walne AJ, Vulliamy T, Beswick R, Kirwan M and Dokal I (2010) Mutations in C16orf57 and normal length telomeres unify a subset of patients with dyskeratosis congenita, poikiloderma with neutropenia and Rothmund-Thomson syndrome Hum. Mol. Genet 19:4453-61
Vulliamy T, Beswick R, Kirwan M, Marrone M, Digweed M, Walne A, Dokal I (2008) Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita. Proc Natl Acad Sci USA, 105:8073-8078.
Vulliamy T, Marrone A, Szydlo R, Walne A, Mason PJ, Dokal I (2004) Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nature Genetics 36:447-449
Vulliamy TJ, Marrone A, Dokal I, Mason PJ (2002) Association between aplastic anaemia and mutations in telomerase RNA. Lancet, 359:2168-2170.
Vulliamy T, Marrone A, Goldman F, Dearlove A, Bessler M, Mason PJ, Dokal I (2001) The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 413:432-435.
Heiss NS*, Knight SW*, Vulliamy TJ*, Klauk SM, Wiemann S, Mason PJ, Poustka A, Dokal I (1998) X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nature Genetics 19:32-38
MBBS, FunMed, Genetics Module including workshop Human Development (HD2) Graduate Entry Programme
MBBS Student Mentor
Topics for PhD supervision:
Functional characterisation of mutations in dyskeratosis congenita
Centre for Genomics and Child Health Blizard Institute Barts and The London School of Medicine and Dentistry Blizard Building 4 Newark Street Whitechapel London E1 2AT