In this section
Epigenetic regulation of myeloma
Multiple myeloma is in many ways a disease driven by inappropriate gene expression. It is characterised by the aberrant activation of gene regulatory elements known as enhancers, stimulating the upregulation of key oncogenes. Blocking this behaviour is therefore a promising strategy for myeloma treatment, and many therapeutic strategies directly or indirectly target gene regulatory pathways.
The lab studies the epigenetic regulation of gene expression, focused on the way these processes are dysregulated in multiple myeloma. We have a particular interest in understanding the role of oncogenic enhancer activity in driving myeloma-specific transcriptional profiles, and identifying the factors responsible for this behaviour. A major goal of the lab is to identify potential therapeutic targets that could be developed as novel therapies for multiple myeloma.
We use a variety of high-throughput genomics techniques to study the chromatin landscape, including ChIP-seq, ATAC-seq and RNA-seq. We have optimised TOPmentation, a small cell-number technique that allows us to characterise the chromatin profile of myeloma patient samples. In addition, we use the 3C technology Micro-Capture-C to map the physical association of enhancers and promoters. By combining these techniques with genetic and pharmacological manipulation of myeloma cell lines, we are able to explore mechanistically enhancer function and regulation.
Mechanisms of myeloma drug resistance
Relapse is very common in myeloma after initial treatment. Patients typically enter remission following treatment, but invariably relapse, often with resistance to one or more of these drugs. There is therefore a pressing need to understand the mechanisms that drive this resistance to find ways to counteract it. We are working to identify and understand epigenetic mechanisms that drive drug resistance via changes in gene expression, which therefore may be reversed to resensitise cells to therapy.
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Nick Crump (he/him)
Kay Kendall Leukaemia Fund Intermediate Fellow
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Jinglin Zhou (he/him)
PhD student
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Jason Taslim (he/him)
Research assistant
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Sophie Ball (she/her)
PhD student
@article{Crump:2019:10.1007/s00018-019-03143-z,
author = {Crump, NT and Milne, TA},
doi = {10.1007/s00018-019-03143-z},
journal = {Cellular and Molecular Life Sciences},
pages = {2885--2898},
title = {Why are so many MLL lysine methyltransferases required for normal mammalian development?},
url = {http://dx.doi.org/10.1007/s00018-019-03143-z},
volume = {76},
year = {2019}
}
TY - JOUR
AB - The mixed lineage leukemia (MLL) family of proteins became known initially for the leukemia link of its founding member. Over the decades, the MLL family has been recognized as an important class of histone H3 lysine 4 (H3K4) methyltransferases that control key aspects of normal cell physiology and development. Here, we provide a brief history of the discovery and study of this family of proteins. We address two main questions: why are there so many H3K4 methyltransferases in mammals; and is H3K4 methylation their key function?
AU - Crump,NT
AU - Milne,TA
DO - 10.1007/s00018-019-03143-z
EP - 2898
PY - 2019///
SN - 1420-682X
SP - 2885
TI - Why are so many MLL lysine methyltransferases required for normal mammalian development?
T2 - Cellular and Molecular Life Sciences
UR - http://dx.doi.org/10.1007/s00018-019-03143-z
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000476550200003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR - https://link.springer.com/article/10.1007/s00018-019-03143-z
VL - 76
ER -