Dr Michael Jackson
- Email: email@example.com
- Telephone: +44 (0) 191 241 8677
- Address: Institute of Genetic Medicine
International Centre for Life
Newcastle upon Tyne
Institute of Genetic Medicine
The Genetics of Paediatric Cancers
The identification of genes involved in cancer is a cornerstone of molecular oncology and has led to a vast improvement in our understanding of tumourigenesis, identified a wide variety of therapeutic targets, and in some cases led to dramatic improvement in patient survival due to subsequent targeted intervention. Global approaches to gene identification in adult cancers have identified mutations in a much larger number, and wider variety, of genes than previously expected. However, the causative changes in many childhood cancers, where mutation rates are an order of magnitude lower, remain less well understood, and additional methods, such as comparative analyses are likely to be particularly valuable. Historically, most of our cancer research has been on neuroblastoma, but recently we have using a transpositional mutagen called Sleeping Beauty to alter the incidence and latency of cancer formation in a mouse model of medulloblastoma, a malignant childhood brain tumour. This work, performed in collaboration with the Northern Institute for Cancer Research in Newcastle, has identified mutations in linked networks of transcription factors which control neuronal development and proliferation. These appear to underpin cancer progression in this model, and using both direct analyses of human tumours, and experimental manipulation of genes within these networks, we hope to identify the key genetic events involved in tumourigenesis and identify novel therapeutic targets. In addition, I am involved in several projects with a focus on colorectal cancer, and these are in collaboration with Professor Sir John Burn who is also within the Institute of Genetic Medicine.
Transcriptional Diversity: Form and Function
RNAs where the exon order is shuffled relative to the underlying genomic sequence were first identified over 20 years ago, but until recently have been assumed primarily to be rare errors of known transcriptional processes. However, advances in sequencing technologies have allowed the abundance and distribution of RNA species to be analysed at very high resolution, and we and others have now established that shuffled transcripts are not only common, they can be the most abundant transcripts from some human genes. In addition, they are often circular, are largely cytoplasmic, and several non-coding circular transcripts have recently been shown to act as micro RNA sponges, indicating that they can have important functions in gene regulation. Because these transcripts extend our current understanding of how genetic information is both processed and functions, it is important to establish how they are generated and roles for the vast majority of these transcripts remain to be established. We are currently using high depth sequencing techniques, direct experimental manipulation of individual genes, and gene knockdown approaches, to perform mechanistic and functional analyses in both human and murine cell culture models.
Dr. Abd Al Hassain PhD. Research Associate
Hani Al-Afghani. PhD Student
Ginikachukwu Izuogo. PhD Student
Lisa Redford. PhD Student
Harsh Sheth. PhD student
Module Leader: BGM2058 Phylogenetics and Evolution.
Lecturer: BGM2057The genome: cell cycle, organisation, expression and function.
Lecturer: MMB8029 Medical Genomics.
Lecturer: MMB8031 Developmental Genetics.
MRes Strand leader: Medical Genetics.
- Łastowska M, Al-Afghani H, Al-Balool HH, Sheth H, Mercer E, Coxhead JM, Redfern CPF, Peters H, Burt AD, Santibanez-Koref M, Bacon CM, Chesler L, Rust AG, Adams DJ, Williamson D, Clifford SC, Jackson MS. Identification of a neuronal transcription factor network involved in medulloblastoma development. Acta Neuropathologica Communications 2013, 1, 35.
- Al-Balool HH, Weber D, Liu Y, Wade M, Guleria K, Nam PL, Clayton J, Rowe W, Coxhead J, Irving J, Elliott DJ, Hall AG, Santibanez-Koref M, Jackson MS. Post-transcriptional exon shuffling events in humans can be evolutionarily conserved and abundant. Genome Research 2011, 21(11), 1788-1799.
- Ehrmann I, Dalgliesh C, Tsaousi A, Paronetto MP, Heinrich B, Kist R, Cairns P, Li W, Mueller C, Jackson M, Peters H, Nayernia K, Saunders P, Mitchell M, Stamm S, Sette C, Elliott DJ. Haploinsufficiency of the germ cell-specific nuclear RNA binding protein hnRNP G-T prevents functional spermatogenesis in the mouse. Human Molecular Genetics 2008, 17(18), 2803-2818.
- Moore HC, Wood KM, Jackson MS, Lastowska MA, Hall D, Imrie H, Redfern CPF, Lovat PE, Ponthan FM, O'Toole KT, Lunec J, Tweddle DA. Histological profile of tumours from MYCN transgenic mice. Journal of Clinical Pathology 2008, 61(10), 1098-1103.
- Viprey VF, Lastowska MA, Corrias MV, Swerts K, Jackson MS, Burchill SA. Minimal disease monitoring by QRT–PCR: guidelines for identification and systematic validation of molecular markers prior to evaluation in prospective clinical trials. Journal of Pathology 2008, 216(2), 245-252.
- Cheng AJ, Ching Cheng N, Ford J, Smith J, Murray JE, Flemming C, Lastowska M, Jackson MS, Hackett CS, Weiss WA, Marshall GM, Kees UR, Norris MD, Haber M. Cell lines from MYCN transgenic murine tumours reflect the molecular and biological characteristics of human neuroblastoma. European Journal of Cancer 2007, 43(9), 1467-1475.
- Łastowska MA, Viprey V, Santibanez-Koref MF, Wappler I, Peters HH, Cullinane C, Roberts P, Hall AG, Tweddle DA, Pearson ADJ, Lewis I, Burchill S, Jackson MS. Identification of candidate genes involved in neuroblastoma progression by combining genomic and expression microarrays with survival data. Oncogene 2007, 26(53), 7432-7444.
- Venables JP, Strain L, Routledge D, Bourn D, Powell HM, Warwicker P, Diaz-Torres ML, Sampson A, Mead P, Webb M, Pirson Y, Jackson MS, Hughes A, Wood KM, Goodship JA, Goodship THJ. Atypical haemolytic uraemic syndrome associated with a hybrid complement gene. PLoS Medicine 2006, 3(10), e431 (1957-1967).
- Heinen S, Sanchez-Corral P, Jackson MS, Strain L, Goodship JA, Kemp EJ, Skerka C, Jokiranta TS, Meyers K, Wagner E, Robitaille P, Esparza-Gordillo J, Rodriguez de Cordoba S, Zipfel PF, Goodship THJ. De novo gene conversion in the RCA gene cluster (1q32) causes mutations in complement factor H associated with atypical hemolytic uremic syndrome. Human Mutation 2006, 27(3), 292-293.
- Jackson MS, Oliver K, Loveland J, Humphray S, Dunham I, Rocchi M, Viggiano L, Park JP, Hurles ME, Santibanez-Koref M. Evidence for widespread reticulate evolution within human duplicons. American Journal of Human Genetics 2005, 77(5), 824-840.
- Mudge JM, Jackson MS. Evolutionary implications of pericentromeric gene expression in humans. Cytogenetic and Genome Research 2005, 108(1-3), 47-57.
- Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blöcker H, Durbin R, Sulston JE, Hubbard T, Jackson MS, Bentley DR, Beck S, Rogers J, Dunham I. DNA sequence and analysis of human chromosome 9. Nature 2004, 429, 369-74.
- Tonkin ET, Smith M, Eichhorn P, Jones S, Imamwerdi B, Lindsay S, Jackson M, Wang T-J, Ireland M, Burn J, Krantz ID, Carr P, Strachan T. A giant novel gene undergoing extensive alternative splicing is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3. Human Genetics 2004, 115(2), 139-148.
- Lastowska M, Chung Y-J, Ching NC, Haber M, Norris MD, Kees UR, Pearson ADJ, Jackson MS. Regions Syntenic to Human 17q Are Gained in Mouse and Rat Neuroblastoma. Genes Chromosomes and Cancer 2004, 40(2), 158-163.
- Jackson M. Duplicate, decouple, disperse: The evolutionary transience of human centromeric regions. Current Opinion in Genetics and Development 2003, 13(6), 629-635.
- Ventura M, Mudge JM, Palumbo V, Burn S, Blennow E, Pierluigi M, Giorda R, Zuffardi O, Archidiacono N, Jackson MS, Rocchi M. Neocentromeres in 15q24-26 map to duplicons which flanked an ancestral centromere in 15q25. Genome Research 2003, 13(9), 2059-2068.
- Guy J, Hearn T, Crosier M, Mudge J, Viggiano L, Koczan D, Thiesen H-J, Bailey JA, Horvath JE, Eichler EE, Earthrowl ME, Deloukas P, French L, Rogers J, Bentley D, Jackson MS. Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10p. Genome Research 2003, 13(2), 159-172.
- Lastowska, M., Cotterill, C., Bown, N., Cullinane, C., Variend, S., Lunec, J., Strachan, T., Pearson, A.D.J., Jackson, M.S. Breakpoint position on 17q identifies the most aggressive neuroblastoma tumors. Genes Chromosomes and Cancer 2002, 34(4), 428-436.
- Crosier M, Viggiano L, Guy J, Misceo D, Stones R, Wei WB, Hearn T, Ventura M, Archidiacono N, Rocchi M, Jackson MS. Human paralogs of KIAA0187 were created through independent pericentromeric-directed and chromosome-specific duplication mechanisms. Genome Research 2002, 12(1), 67-80.
- Phillips HM, Renforth GL, Spalluto C, Hearn T, Curtis ARJ, Craven L, Havarani B, Clement-Jones M, English C, Stumper O, Salmon T, Hutchinson S, Jackson MS, Wilson DI. Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis. Genomics 2002, 79(4), 475-478.
- Lastowska MA, Cullinane C, Variend S, Cotterill SJ, Bown NP, O'Neill S, Mazzocco K, Roberts P, Nicholson J, Ellershaw C, Pearson ADJ, Jackson MS. Comprehensive genetic and histopathologic study reveals three types of neuroblastoma tumors. Journal of Clinical Oncology 2001, 19(12), 3080-3090.
- Lastowska M, Van Roy N, Bown N, Roberts P, Speleman F, Lunec J, Strachan T, Pearson ADJ, Jackson MS. Molecular cytogenetic definition of 17q translocation breakpoints in neuroblastoma. Pediatric Blood and Cancer 2001, 36(1), 20-23.
- Guy J, Spalluto C, McMurray A, Hearn T, Crosier M, Viggiano L, Miolla V, Archidiacono N, Rocchi M, Scott C, Lee PA, Sulston J, Rogers J, Bentley D, Jackson MS. Genomic sequence and transcriptional profile of the boundary between pericentrometric satellites and genes on human chromosome arm 10q. Human Molecular Genetics 2000, 9(13), 2029-2042.
- Jackson MS, Rocchi M, Thompson G, Hearn T, Crosier M, Guy J, Kirk D, Mulligan L, Ricco A, Piccininni S, Marzella R, Viggiano L, Archidiacono N. Sequences flanking the centromere of human chromosome 10 are a complex patchwork of arm-specific sequences, stable duplications and unstable sequences with homologies to telomeric and other centromeric locations. Human Molecular Genetics 1999, 8(2), 205-215.
- Lastowska, M., Van Roy, N., Bown, N.P., Speleman, F., Lunec, J., Strachan, T., Pearson, A.D.J., Jackson, M.S. Molecular cytogenetic delineation of 17q translocation breakpoints in neuroblastoma cell lines. Genes Chromosomes and Cancer 1998, 23(2), 116-122.
- Jackson MS, See CG, Mulligan LM, Lauffart BF. A 9.75-Mb map across the centromere of human chromosome 10. Genomics 1996, 33, 258-70.
- Tunnacliffe A, Jackson MS, Gardner E, Love DR, Moore JK, Mole SE, Mulligan LM, Graham A, Finocchiaro G, Orstavik S, Ponder BA. A multiple interval physical map of the pericentromeric region of human chromosome 10. Human Genetics 1994, 93, 313-318.
- Jackson MS, Slijepcevic P, Ponder BA. The organisation of repetitive sequences in the pericentromeric region of human chromosome 10. Nucleic Acids Research 1993, 21, 5865-5874.
- Tunnacliffe A, Liu L, Moore JK, Leversha MA, Jackson MS, Papi L, Ferguson-Smith MA, Thiesen HJ, Ponder BA. Duplicated KOX zinc finger gene clusters flank the centromere of human chromosome 10: evidence for a pericentric inversion during primate evolution. Nucleic Acids Research 1993, 21, 1409-1417.
- Mole SE, Jackson MS, Tokino T, Nakamura Y, Ponder BA. Assignment of fifty-four cosmid clones to five regions of chromosome 10. Genomics 1993, 15, 457-458.
- Jackson MS, Mole SE, Ponder BA. Characterisation of a boundary between satellite III and alphoid sequences on human chromosome 10. Nucleic Acids Research 1992, 20, 4781-4787.
- Mackay, T.F.C., Lyman, R.F., Jackson, M.S., Terzian, C. & Hill, W.G. Polygenic mutation in Drosophila melanogaster: Estimates from divergence among inbred strains. Evolution 1992, 46, 300-316.
- Mackay TF, Lyman RF, Jackson MS. Effects of P element insertions on quantitative traits in Drosophila melanogaster. Genetics 1992, 130, 315-332.
- Jackson MS, Black DM, Dover GA. Amplification of KP elements associated with the repression of hybrid dysgenesis in Drosophila melanogaster. Genetics 1988, 120, 1003-1013.
- Black DM, Jackson MS, Kidwell MG, Dover GA. KP elements repress P-induced hybrid dysgenesis in Drosophila melanogaster. EMBO J 1987, 6, 4125-4135.
- Grellscheid S, Dalgliesh C, Storbeck M, Best A, Liu Y, Jakubik M, Mende Y, Ehrmann I, Curk T, Rossbach K, Bourgeois CF, Stévenin J, Grellscheid D, Jackson MS, Wirth B, Elliott DJ. Identification of evolutionarily conserved exons as regulated targets for the splicing activator tra2β in development. PLoS Genetics 2011, 7(12), e1002390.
- Alhasan A, Izuogu OG, Al-Balool HH, Steyn JS, Evans A, Colzani M, Ghevaert C, Mountford JC, Marenah L, Elliott DJ, Santibanez-Koref M, Jackson MS. Circular RNA enrichment in platelets is a signature of transcriptome degradation. Blood 2016, 127(9), E1-E11.
- Izuogu OG, Alhasan AA, Alafghani HM, Santibanez-Koref M, Elliot DJ, Jackson MS. PTESFinder: a computational method to identify post-transcriptional exon shuffling (PTES) events. BMC Bioinformatics 2016, 17(31).
- Cheetham T, Plumb E, Callaghan J, Jackson M, Michaelis L. Dietary restriction causing iodine-deficient goitre. Archives of Disease in Childhood 2015, 100(8), 784-786.
- Sheth H, Jackson MS, Koref MS, Parikh K, Sheth J, Sheth F, Tyson J, Daly AK, Burn J. Relevance of genetic factors to warfarin dosing in India. Blood 2015, 126(4).