Projects per year
Our overarching research theme is to understand how cells establish and maintain their specific identities. Thus, what are the factors that control and enable genes to be expressed in one type of cell and not another? How does this go wrong in cancer and can we reprogramme gene expression or even reset it back to a stem cell state?
DNA within a cell nucleus is packaged into chromatin and in order for a gene to be expressed, the chromatin needs to be modified so that the DNA encoding the gene is accessible to transcription factors. “Epigenetics” is the study of chromatin and DNA modifications.
Epigenetic Barriers and Cell Identity
Higher-order-chromatin-structure and epigenetic modifications to DNA and histones shape the genome within the nucleus. We are investigating how these mechanisms come together to constitute cell identity and provide the cell with a memory of its developmental origins. Understanding these fundamental questions about cell identity will shed light on how these mechanisms are highjaacked during tumorigenesis and metastasis as well as advance the diverse applications of stem cell research.
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.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
- QH Natural history
- QH426 Genetics
- epigenetics genomic imprinting
- DNA methylation 5-hydroxymethylation
- chromatin structure
- cell migration
- R Medicine › RB Pathology
- Breast cancer; Colon Cancer
- pregnancy and breast cancer
- 1 Similar Profiles
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Sero, J., Cevik, V., Gurevich, D., Jungwirth, U., Kelsh, R., Koumanov, F., Kyprianou, A., Laabei, M., Licchesi, J., Murrell, A., Pascu, S., Turner, L., Walko, G., Ward, A., Ward, S., Williams, R. & Zachariadis, M.
1/08/22 → 31/07/23
Project: Research council
1/04/21 → 31/03/24
Project: UK charity
Two stages of genome wide 5-hydroxymethylcytosine (5hmC) reprogramming during colorectal carcinogenesis and liver metastasis
20/01/20 → 23/10/23
Project: Research council
1/01/17 → 28/02/21
Project: Research council
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 journal › Article › peer-reviewOpen Access6 Citations (SciVal)
Apc Min/+ tumours and normal mouse small intestines show linear metabolite concentration and DNA cytosine hydroxymethylation gradients from pylorus to colonMadhu, B., Uribe-Lewis, S., Bachman, M., Murrell, A. & Griffiths, J. R., 12 Aug 2020, In: Scientific Reports. 10, 1, 13616.
Research output: Contribution to journal › Article › peer-reviewOpen Access
Pisignano, G., Pavlaki, I. & Murrell, A., 9 Apr 2019, In: Essays in Biochemistry. 63, 1, p. 177-186 10 p.
Research output: Contribution to journal › Review article › peer-reviewOpen AccessFile7 Citations (SciVal)125 Downloads (Pure)
HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancerRoss-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, , 9 Oct 2016, In: Oncotarget. 7, 46, p. 74734-74746 13 p.
Research output: Contribution to journal › Article › peer-reviewOpen Access28 Citations (SciVal)
Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions: 2Stojic, 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 journal › Article › peer-reviewOpen Access40 Citations (SciVal)104 Downloads (Pure)