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:2025:10.1002/bies.70006,
author = {Crump, NT and Milne, TA},
doi = {10.1002/bies.70006},
journal = {BioEssays},
title = {Is enhancer function driven by protein–protein Interactions? From bacteria to leukemia},
url = {http://dx.doi.org/10.1002/bies.70006},
volume = {47},
year = {2025}
}
TY - JOUR
AB - The precise regulation of the transcription of genes is essential for normal development and for the maintenance of life. Aberrant gene expression changes drive many human diseases. Despite this, we still do not completely understand how precise gene regulation is controlled in living systems. Enhancers are key regulatory elements that enable cells to specifically activate genes in response to environmental cues, or in a stage or tissue-specific manner. Any model of enhancer activity needs to answer two main questions: (1) how enhancers are able to identify and act on specific genes and (2) how enhancers influence transcription. To address these points, we first outline some of the basic principles that can be established from simpler prokaryotic systems, then discuss recent work on aberrant enhancer activity in leukemia. We argue that highly specific protein–protein interactions are a key driver of enhancer-promoter proximity, allowing enhancer-bound factors to directly act on RNA polymerase and activate transcription.
AU - Crump,NT
AU - Milne,TA
DO - 10.1002/bies.70006
PY - 2025///
SN - 0265-9247
TI - Is enhancer function driven by protein–protein Interactions? From bacteria to leukemia
T2 - BioEssays
UR - http://dx.doi.org/10.1002/bies.70006
UR - https://doi.org/10.1002/bies.70006
VL - 47
ER -