|Born||13 January 1951, 1951 (age 70)|
Douglas Roland Higgs (born 13 January 1951)FRS is a Professor of Molecular Haematology and director of the Weatherall Institute of Molecular Medicine, at the University of Oxford. He is known for his work on the regulation of alpha-globin and the genetics of alpha-thalassemia. He is currently working in understanding the mechanisms by which any mammalian gene is switched on and off during differentiation and development.
He was educated at Alleyn's School and qualified in medicine at King's College Hospital Medical School in 1974, and trained as a haematologist.He became a registrar in Haematology at Kings College Hospital in 1976.
He joined the Molecular Haematology Unit of the Medical Research Council at Oxford in 1977. In 1996 he was appointed Ad Hominem Professor of Molecular Haematology, in 2001 he became a director of the MRC Molecular Haematology Unit.In 2012 Higgs was appointed director of the Wetherall Institute of Molecular Medicine. Higgs is a Senior Kurti Fellow at Brasenose College, Oxford.
Gibbons, Richard J; Picketts, David J; Villard, Laurent; Higgs, Douglas R (1995). "Mutations in a putative global transcriptional regulator cause X-linked mental retardation with α-thalassemia (ATR-X syndrome)". Cell. 80 (6): 837–845. doi: 10.1016/0092-8674(95)90287-2 . PMID 7697714. S2CID 16411046.
Tufarelli, Cristina; Stanley, Jackie A Sloane; Garrick, David; Sharpe, Jackie A; Ayyub, Helena; Wood, William G; Higgs, Douglas R (2003). "Transcription of antisense RNA leading to gene silencing and methylation as a novel cause of human genetic disease". Nature Genetics. 34 (2): 157–165. doi:10.1038/ng1157. ISSN 1546-1718. PMID 12730694. S2CID 7226446.
Higgs, D. R.; Goodbourn, S. E. Y.; Lamb, J.; Clegg, J. B.; Weatherall, D. J.; Proudfoot, N. J. (1983). "α-Thalassaemia caused by a polyadenylation signal mutation". Nature. 306 (5941): 398–400. doi:10.1038/306398a0. ISSN 1476-4687. PMID 6646217. S2CID 4332750.
Wilkie, Andrew O. M.; Lamb, Janette; Harris, Peter C.; Finney, Roger D.; Higgs, Douglas R. (1990). "A truncated human chromosome 16 associated with α thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n". Nature. 346 (6287): 868–871. doi:10.1038/346868a0. ISSN 1476-4687. PMID 1975428. S2CID 4239520.
Nicholls, R.D.; Fischel-Ghodsian, N.; Higgs, D.R. (1987). "Recombination at the human α-globin gene cluster: Sequence features and topological constraints". Cell. 49 (3): 369–378. doi:10.1016/0092-8674(87)90289-3. PMID 3032452. S2CID 54349888.
De Gobbi, Marco; Viprakasit, Vip; Hughes, Jim R.; Fisher, Chris; Buckle, Veronica J.; Ayyub, Helena; Gibbons, Richard J.; Vernimmen, Douglas; Yoshinaga, Yuko (26 May 2006). "A Regulatory SNP Causes a Human Genetic Disease by Creating a New Transcriptional Promoter". Science. 312 (5777): 1215–1217. doi:10.1126/science.1126431. ISSN 0036-8075. PMID 16728641. S2CID 16044469.
Law, Martin J.; Lower, Karen M.; Voon, Hsiao P.J.; Hughes, Jim R.; Garrick, David; Viprakasit, Vip; Mitson, Matthew; De Gobbi, Marco; Marra, Marco (2010). "ATR-X Syndrome Protein Targets Tandem Repeats and Influences Allele-Specific Expression in a Size-Dependent Manner". Cell. 143 (3): 367–378. doi: 10.1016/j.cell.2010.09.023 . PMID 21029860.
Hughes, Jim R; Roberts, Nigel; McGowan, Simon; Hay, Deborah; Giannoulatou, Eleni; Lynch, Magnus; De Gobbi, Marco; Taylor, Stephen; Gibbons, Richard (2014). "Analysis of hundreds of cis-regulatory landscapes at high resolution in a single, high-throughput experiment". Nature Genetics. 46 (2): 205–212. doi:10.1038/ng.2871. ISSN 1546-1718. PMID 24413732. S2CID 205348099.
Higgs, Douglas R.; Gibbons, Richard J.; McDowell, Tarra L.; Raman, Sundhya; O'Rourke, Delia M.; Garrick, David; Ayyub, Helena (2000). "Mutations in ATRX, encoding a SWI/SNF-like protein, cause diverse changes in the pattern of DNA methylation". Nature Genetics. 24 (4): 368–371. doi:10.1038/74191. ISSN 1546-1718. PMID 10742099. S2CID 8847855.
Hay, Deborah; Hughes, Jim R; Babbs, Christian; Davies, James O J; Graham, Bryony J; Hanssen, Lars L P; Kassouf, Mira T; Oudelaar, A Marieke; Sharpe, Jacqueline A (2016). "Genetic dissection of the α-globin super-enhancer in vivo". Nature Genetics. 48 (8): 895–903. doi:10.1038/ng.3605. ISSN 1546-1718. PMC 5058437 . PMID 27376235.
Thalassemias are inherited blood disorders characterized by decreased hemoglobin production. Symptoms depend on the type and can vary from none to severe. Often there is mild to severe anemia. Anemia can result in feeling tired and pale skin. There may also be bone problems, an enlarged spleen, yellowish skin, and dark urine. Slow growth may occur in children.
Sir Gregory Paul Winter is a Nobel Prize-winning British molecular biologist best known for his work on the therapeutic use of monoclonal antibodies. His research career has been based almost entirely at the MRC Laboratory of Molecular Biology and the MRC Centre for Protein Engineering, in Cambridge, England.
Alpha-thalassemia is a form of thalassemia involving the genes HBA1 and HBA2. Thalassemias are a group of inherited blood conditions which result in the impaired production of hemoglobin, the molecule that carries oxygen in the blood. Normal hemoglobin consists of two alpha chains and two beta chains; in alpha-thalassemia, there is a quantitative decrease in the amount of alpha chains, resulting in fewer normal hemoglobin molecules. Furthermore, alpha-thalassemia leads to the production of unstable beta globin molecules which cause increased red blood cell destruction. The degree of impairment is based on which clinical phenotype is present.
Sir David John Weatherall, was a British physician and researcher in molecular genetics, haematology, pathology and clinical medicine.
Alpha-thalassemia mental retardation syndrome (ATRX), also called alpha-thalassemia X-linked mental retardation, nondeletion type or ATR-X syndrome, is an X-linked recessive condition associated with a mutation in the ATRX gene. Males with this condition tend to be moderately intellectually disabled and have physical characteristics including coarse facial features, microcephaly, hypertelorism, a depressed nasal bridge, a tented upper lip and an everted lower lip. Mild or moderate anemia, associated with alpha-thalassemia, is part of the condition. Females with this mutated gene have no specific signs or features, but if they do, they may demonstrate skewed X chromosome inactivation.
Hemoglobin subunit beta, is a globin protein, coded for by the HBB gene, which along with alpha globin (HBA), makes up the most common form of haemoglobin in adult humans, hemoglobin A (HbA). It is 147 amino acids long and has a molecular weight of 15,867 Da. Normal adult human HbA is a heterotetramer consisting of two alpha chains and two beta chains.
Krueppel-like factor 1 is a protein that in humans is encoded by the KLF1 gene. The gene for KLF1 is on the human chromosome 19 and on mouse chromosome 8. Krueppel-like factor 1 is a transcription factor that is necessary for the proper maturation of erythroid cells.
Hemoglobin subunit delta is a protein that in humans is encoded by the HBD gene.
Hemoglobin subunit gamma-1 is a protein that in humans is encoded by the HBG1 gene.
Hemoglobin subunit epsilon is a protein that in humans is encoded by the HBE1 gene.
Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) is a protein that in humans is encoded by the ATRX gene.
Hemoglobin subunit zeta is a protein that in humans is encoded by the HBZ gene.
Hemoglobin, alpha pseudogene 1, also known as HBAP1, is a human gene.
Hemoglobin subunit theta-1 is a protein that in humans is encoded by the HBQ1 gene.
Hemoglobin, alpha 2 also known as HBA2 is a gene that in humans codes for the alpha globin chain of hemoglobin.
Ketan Jayakrishna Patel is Director of the MRC Weatherall Institute of Molecular Medicine and the MRC Molecular Haematology Unit at the University of Oxford. Until 2020 he was a tenured principal investigator at the Medical Research Council (MRC) Laboratory of Molecular Biology (LMB).
David Chaim Rubinsztein FRS FMedSci is the Deputy Director of the Cambridge Institute of Medical Research (CIMR), the Academic Lead of the Alzheimer's Research UK (ARUK) Cambridge Drug Discovery Institute, Professor of Molecular Neurogenetics at the University of Cambridge. and a UK Dementia Research Institute Professor.
Sir Andrew James McMichael, is an immunologist, Professor of Molecular Medicine, and previously Director of the Weatherall Institute of Molecular Medicine at the University of Oxford. He is particularly known for his work on T cell responses to viral infections such as influenza and HIV.
Swee Lay Thein is a Malaysian haematologist and physician-scientist who is Senior Investigator at the National Institutes of Health. She works on the pathophysiology of haemoglobin disorders including sickle cell disease and thalassemia.
The MRC Weatherall Institute of Molecular Medicine at the University of Oxford is a research institute located at the John Radcliffe Hospital in Oxford. Founded in 1989 by Sir David Weatherall, the institute focuses on furthering our understanding of clinical medicine at a molecular level. It was one of the first institutes of its kind in the world to be dedicated to research in this area.