• 4 SOUTH 0.56

Accepting Doctoral Students

20042020

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Personal profile

Research interests

Current Research

Higher-order-chromatin-structure and epigenetic modifications to DNA and histones shape the genome within the nucleus. We are investigating how tumorigenesis and metastasis disrupt genome organisation and how this leads to the aberrant expression of several genes related to cancer cell survival.

Genomic Imprinting as a Model Epigenetic System

The phenomenon of genomic imprinting is an ideal model-system for functional epigenetic analysis. Imprinted genes are a network of epigenetically regulated genes involved in foetal growth. They are expressed from one allele in a parent-of-origin specific manner and are controlled by cooperating epigenetic mechanisms that are widely applicable to the understanding of genome organisation and gene expression in general. In addition to DNA methylation changes, these mechanisms include transcriptional interference and/ or recruitment of chromatin modifiers by noncoding RNAs and partitioning the genome into looping domain structures bordered by CTCF and cohesin.

Long Range Epigenetic Silencing in Cancer

In cancer several contiguous genes along a chromosome region can be simultaneously silenced. This is known as long range epigenetic silencing (LRES). Our goal is to understand how LRES originates and spreads. It is likely that this process employs similar mechanisms to genomic imprinting. We are studying an LRES region that contains the imprinted tumour suppressor gene DIRAS3 and an associated long non coding RNA, both of which are silenced in multiple cancers including breast and prostate cancer.

Epigenetic Reprogramming during metastasis

When cells metastasise from a primary cancer site to a new site, they undergo epigenetic reprogramming events that enable them to migrate, infiltrate, adapt and colonise a new environment. Our future goal is to identify the triggers of these epigenetic changes with a view to prevent metastasis. At present we are looking at colon cancer and liver metastasis and focusing on changes in DNA methylation and its demethylation intermediates such as 5-hydroxymethylcytosine.

Keywords

  • QH Natural history
  • QH426 Genetics
  • epigenetics genomic imprinting
  • DNA methylation 5-hydroxymethylation
  • chromatin structure
  • cell migration
  • R Medicine › RB Pathology
  • Breast cancer; Colon Cancer
  • Metastasis
  • pregnancy and breast cancer

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Projects

Research Output

5-hydroxymethylcytosine and gene activity in mouse intestinal differentiation

Uribe-Lewis, S., Carroll, T., Menon, S., Nicholson, A., Manasterski, P. J., Winton, D. J., Buczacki, S. J. A. & Murrell, A., 17 Jan 2020, In : Scientific Reports. 10, 1, 546.

Research output: Contribution to journalArticle

Open Access
1 Citation (Scopus)

Being in a loop: how long non-coding RNAs organise genome architecture

Pisignano, G., Pavlaki, I. & Murrell, A., 9 Apr 2019, In : Essays in Biochemistry. 63, 1, p. 177-186 10 p.

Research output: Contribution to journalReview article

Open Access
File
4 Citations (Scopus)
8 Downloads (Pure)

HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer

Ross-Adams, H., Ball, S., Lawrenson, K., Halim, S., Russell, R., Wells, C., Strand, S. H., Ørntoft, T. F., Larson, M., Armasu, S., Massie, C. E., Asim, M., Mortensen, M. M., Borre, M., Woodfine, K., Warren, A. Y., Lamb, A. D., Kay, J., Whitaker, H., Ramos-Montoya, A. & 8 others, Murrell, A., Sørensen, K. D., Fridley, B. L., Goode, E. L., Gayther, S. A., Masters, J., Neal, D. E. & Mills, I. G., 9 Oct 2016, In : Oncotarget. 7, 46, p. 74734-74746 13 p.

Research output: Contribution to journalArticle

Open Access
  • 22 Citations (Scopus)

    Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions: 2 

    Stojic, L., Niemczyk, M., Orjalo, A., Ito, Y., Ruijter, A. E. M., Uribe-Lewis, S., Joseph, N., Weston, S., Menon, S., Odom, D. T., Rinn, J., Gergely, F. & Murrell, A., 2 Feb 2016, In : Nature Communications. 7, 10406.

    Research output: Contribution to journalArticle

    Open Access
  • 27 Citations (Scopus)
    104 Downloads (Pure)