Professor Karen Steel

Karen studies the genetics of deafness, using the mouse as a model to identify the genes involved and to understand the molecular, cellular and physiological mechanisms involved.

Karen graduated with a degree in Genetics & Zoology from the University of Leeds in 1974 and a PhD in Genetics from the Department of Human Genetics and Biometry, University College London, in 1978.

Following a postdoctoral fellowship at the Medical Research Council (MRC) Institute of Hearing Research in Nottingham and a postdoctoral position at the Institut für Zoologie in München, Germany, she returned to the UK in 1983 to take on a research position at the MRC Institute of Hearing Research in Nottingham. She was made an honorary Professor of Genetics at the University of Nottingham in 1995. In October 2003, Karen Steel joined the Wellcome Trust Sanger Institute as Principal Investigator to lead her team working on the genetics of deafness as well as establishing the Mouse Genetics Programme.

During her career, Karen Steel has served on many national and international bodies, including the Hearing Research editorial board; Mammalian Genome editorial board; Scientific Advisory Board of the Mouse Genome Database; Organising Committee of the Molecular Biology of Hearing and Deafness Conference; International Mouse Genome Nomenclature Committee; Council of Association for Research in Otolaryngology; and she is currently the President of the International Mammalian Genome Society. She has also been an expert witness to House of Lords Select Committee on Ageing, scientific advisor to the charities Deafness Research UK and SENSE, deputy Chairman of the MRC Neurosciences Board, editor of the Hereditary Deafness Newsletter and member of the Wellcome Trust Neurosciences and Mental Health Funding Committee.

In 1998, Karen was the recipient of the Kresge-Mirmelstein prize for excellence in hearing research (New Orleans), was elected Fellow of the Academy of Medical Sciences (London) in 2004 and Fellow of the Royal Society in 2009.

Her early interest was in the genetics of deafness. In the 1980s, she was the first to demonstrate that lack of melanocytes in the stria vascularis of mice with white spotting (pigmentation defects) caused abnormal strial function leading to deafness. Later on and in collaboration with Steve Brown, she succeeded in identifying the first mouse gene involved in deafness, Myo7a, which is mutated in the shaker1 mouse mutant (Gibson et al. 1995). Several of the deafness genes that she has subsequently worked on or discovered in the mouse have been found to underlie human deafness, including MYO7A, CDH23, MYO6, TMC1, CHD7 and WHRN, (eg Mburu et al. 2003; Bosman et al. 2005; Gibson et al. 1995; Vreugde et al. 2002) and many of the new mouse deafness genes her group is working on will also likely be involved in human deafness.

Karen has been involved in two large-scale mutagenesis programmes. The first used ENU, a powerful chemical mutagen, to create new single base changes randomly in the genome. Offspring from mutagenised males were screened for deafness and balance defects, among many other screens. Karens team, in collaboration with other members of the European consortium that carried out the programme, has identified the causative mutation in around twenty five of the new deaf mutants and characterised their phenotypes in detail. Several new genes previously not known to be involved in deafness have been identified by this programme.

Since joining the Wellcome Trust Sanger Institute, Karen has established the Mouse Genetics Programme, a large-scale effort to generate 250 new mouse mutants each year and screen them for key signs of disease. The mice are created using ES cells targeted by Bill Skarnes and Allan Bradley through the EUCOMM/KOMP programme. Over 300 of these lines now have given germ line transmission of the targeted allele, and colonies are being expanded to feed the phenotyping pipelines. Data on the first 30 lines to be screened are presented on the website or at europhenome.org. As the programme scales up, academic interest in these resources is growing rapidly and mice are being supplied to requestors as they become available. This programme represents a highly cost-effective way of generating new mouse mutants (in terms of funding and mouse numbers) and providing phenotypic information that allows other groups to select lines for further detailed study. The management of this programme has now been passed on to Ramiro Ramirez-Solis.

Selected Publications

• An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice.

  Lewis MA, Quint E, Glazier AM, Fuchs H, De Angelis MH, Langford C, van Dongen S, Abreu-Goodger C, Piipari M, Redshaw N, Dalmay T, Moreno-Pelayo MA, Enright AJ and Steel KP

  Nature genetics2009;41;5;614-8

  PUBMED: 19363478; PMC: 2705913; DOI: 10.1038/ng.369

• Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss.

  Mencía A, Modamio-Høybjør S, Redshaw N, Morín M, Mayo-Merino F, Olavarrieta L, Aguirre LA, del Castillo I, Steel KP, Dalmay T, Moreno F and Moreno-Pelayo MA

  Nature genetics2009;41;5;609-13

  PUBMED: 19363479; DOI: 10.1038/ng.355

• Presence of interstereocilial links in waltzer mutants suggests Cdh23 is not essential for tip link formation.

  Rzadzinska AK and Steel KP

  Neuroscience2009;158;2;365-8

  PUBMED: 18996172; PMC: 2989438; DOI: 10.1016/j.neuroscience.2008.10.012

• The novel mouse mutation Oblivion inactivates the PMCA2 pump and causes progressive hearing loss.

  Spiden SL, Bortolozzi M, Di Leva F, de Angelis MH, Fuchs H, Lim D, Ortolano S, Ingham NJ, Brini M, Carafoli E, Mammano F and Steel KP

  PLoS genetics2008;4;10;e1000238

  PUBMED: 18974863; PMC: 2568954; DOI: 10.1371/journal.pgen.1000238

• Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism.

  Jacobson SG, Cideciyan AV, Aleman TS, Sumaroka A, Roman AJ, Gardner LM, Prosser HM, Mishra M, Bech-Hansen NT, Herrera W, Schwartz SB, Liu XZ, Kimberling WJ, Steel KP and Williams DS

  Human molecular genetics2008;17;15;2405-15

  PUBMED: 18463160; PMC: 2733815; DOI: 10.1093/hmg/ddn140

• Mosaic complementation demonstrates a regulatory role for myosin VIIa in actin dynamics of stereocilia.

  Prosser HM, Rzadzinska AK, Steel KP and Bradley A

  Molecular and cellular biology2008;28;5;1702-12

  PUBMED: 18160714; PMC: 2258769; DOI: 10.1128/MCB.01282-07

• A Myo6 mutation destroys coordination between the myosin heads, revealing new functions of myosin VI in the stereocilia of mammalian inner ear hair cells.

  Hertzano R, Shalit E, Rzadzinska AK, Dror AA, Song L, Ron U, Tan JT, Shitrit AS, Fuchs H, Hasson T, Ben-Tal N, Sweeney HL, de Angelis MH, Steel KP and Avraham KB

  PLoS genetics2008;4;10;e1000207

  PUBMED: 18833301; PMC: 2543112; DOI: 10.1371/journal.pgen.1000207

• Multiple mutations in mouse Chd7 provide models for CHARGE syndrome.

  Bosman EA, Penn AC, Ambrose JC, Kettleborough R, Stemple DL and Steel KP

  Human molecular genetics2005;14;22;3463-76

  PUBMED: 16207732; DOI: 10.1093/hmg/ddi375

• Sox2 is required for sensory organ development in the mammalian inner ear.

  Kiernan AE, Pelling AL, Leung KK, Tang AS, Bell DM, Tease C, Lovell-Badge R, Steel KP and Cheah KS

  Nature2005;434;7036;1031-5

  PUBMED: 15846349; DOI: 10.1038/nature03487