Genetics and Personalised Medicine

Area Academic Contact: Professor Jon Frampton, Director of Research and Knowledge Transfer, College of Medical and Dental Sciences, j.frampton@ham.ac.uk

Research in this area is focused on mechanisms that maintain stem cell phenotype and control the ultimate differentiation into specific cell types relevant to a variety of tissues, incorporating groups from the Research Domains of Genetics & Development, Cancer, and Cardiovascular, Respiratory & Neurological Sciences.  

These fundamental studies embrace strengths in epigenetics, employ genetically engineered fish, mouse and human models, and link closely with medical genetics research to define the molecular basis of inherited human conditions. Some groups also focus on defective repair of DNA damage and how this contributes to both inherited and acquired human disease, including the origin of cancer.

Specific Research Themes

Stem Cells and Gene Regulation

  • Transcriptional Regulation of Adult and Embryonic Stem Cells in Health and Disease
  • Epigenetic Mechanisms of Gene Regulation in Mammals

Rare diseases and genetics

  • Molecular Pathology of Renal Cell Carcinoma
  • Clinical and Molecular Genetic and Epigenetic Investigation of Beckwith-Wiedemann Syndrome
  • Investigating the Molecular Basis of Birt-Hogg-Dube (BHD) Syndrome
  • Identification of New Causative Genes for Congenital Hypothyroidism
  • Research into Von Hippel-Lindau Disease
  • The Role of the Endoplasmic Reticulum Stress Response in the Development of Diabetes in Wolfram Syndrome
  • Zebrafish Regulomics for Human Health

microscopeCancer Genetics and Epigenetics

  • The Role of ATM in the Cell DNA Damage Response and Cancer
  • Regulating the Cellular Response to DNA Damage
  • DNA Damage Response Genes in Lymphoid Malignancies
  • DNA Replication and Genome Stability
  • Cancer Predisposition Pathways
  • Genetic Investigation of the Paediatric Tumours Neuroblastoma and Retinoblastoma

Key Investigators

Recent Research Grants

  • Transcriptional Regulation of Haemopoietic Stem Cells by c-Myb in Health and Disease, Leukaemia & Lymphoma Research
  • WellChild Research Centre for Genetic Epidemiology
  • Clinical and Molecular Genetic and Epigenetic Investigation of Beckwith-Wiedemann Syndrome, Action Medical Research
  • Molecular, Clinical and Therapeutic Studies of Birt Hogg Dube Syndrome, Myrovlitis Trust
  • THYROGENE: Identification of New Causative Genes for Congenital Hypothyroidism, EU Marie Curie
  • Molecular Investigation of Genetic Predisposition to Renal Cancer, Department of Health
  • EURO-WABB: EU Rare Diseases Registry for Wolfram Syndrome, Alstrom Syndrome and Bardet Biedl Syndrome, Commission of the European Communities
  • ZF-HEALTH: Zebrafish Regulomics for Human Health, EU FP7 collaboration
  • Ataxia Telangiectasia (A-T), A-T Like Disorders and Cancer, Cancer Research UK
  • ATM Pathways in CLL: The Development of Targeted Treatment, Leukaemia & Lymphoma Research and Kudos Pharmaceuticals

Recent Publications

  • Ricketts C, et al (2008) Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst, 100: 1260-2.
  • Lefevre P, et al (2008) The LPS-induced transcriptional upregulation of the chicken lysozyme locus involves CTCF eviction and noncoding RNA transcription. Mol Cell, 32: 129-39.
  • García P, et al (2009) Reduction of c-Myb activity compromises normal hematopoietic stem cells and leads to a myeloproliferative phenotype with a novel stem cell basis. EMBO J, 28: 1492-504.
  • Kurian MA, et al (2009) Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia. J Clin Invest, 119: 1595-603.
  • Dallol A, et al (2009) RAN GTPase is a RASSF1A effector involved in controlling microtubule organization. Curr Biol, 19: 1227-32.
  • Gehrig J, et al (2009) Automated high-throughput mapping of promoter-enhancer interactions in zebrafish embryos. Nat Methods, 6: 911-6.
  • Stewart GS, et al (2009) The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell, 136: 420-34.
  • Marston E, et al (2009) Stratification of pediatric ALL by in vitro cellular responses to DNA double-strand breaks provides insight into the molecular mechanisms underlying clinical response. Blood, 113: 117-26.
  • Hoogenkamp M, et al (2009) Early chromatin unfolding by RUNX1: a molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program. Blood, 114: 299-309.
  • Cullinane AR, et al (2010) Mutations in VIPAR cause an arthrogryposis, renal dysfunction and cholestasis syndrome phenotype with defects in epithelial polarization. Nat Genet, 42: 303-12.
  • Morgan NV, et al (2011) Mutation in the TCRα subunit constant gene (TRAC) leads to a human immunodeficiency disorder characterized by a lack of TCRαβ+ T cells. J Clin Invest, 121: 695-702.