Contact

Nicholas Crump

  • Kay Kendall Intermediate Fellow

n.crump@imperial.ac.uk

Follow us on instagram (@crumplab)

Areas of Research

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.

Our team

Nick Crump (he/him)

Nick Crump (he/him)
Kay Kendall Leukaemia Fund Intermediate Fellow

Jinglin Zhou (he/him)

Jinglin Zhou (he/him)
PhD student

Jason Taslim (he/him)

Jason Taslim (he/him)
Research assistant

Sophie Ball (she/her)

Sophie Ball (she/her)
PhD student

Funders

The Kay Kendall Leukaemia Fund

Blood Cancer UK/ Matthew Wilson MM Fund

Imperial Health Charity

The Royal Society

Research Publications

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  • Journal article
    Lau I-J, Bloye G, Smith AL, Harman J, Hamley JC, Sharlandjieva V, Denny NDR, Chahrour C, Li H, Jackson N, Vyas P, Davies J, Hughes JR, Crump N, Milne TAet al., 2026,

    MYB activity drives emergent enhancer activation and enhancer-promoter interactions in acute lymphoblastic leukemia.

    , Blood

    Aberrant enhancer usage is a defining feature of oncogenic transcriptional reprogramming. Therapeutic strategies that disrupt enhancer-driven gene regulation may offer new treatment avenues. MYB is a key hematopoietic transcription factor that is frequently dysregulated in a broad range of cancers and plays a critical role in sustaining malignant cell states, including in aggressive leukemia subtypes such as KMT2A-rearranged (KMT2A-r) leukemias. The molecular mechanisms by which it maintains oncogenic transcription remain incompletely understood. Here, we investigate the role of MYB in directing pathological enhancer activity to drive oncogene expression in leukemia. Using high-resolution Micro-Capture-C, we show that upon MYB degradation, highly defined enhancer-promoter interactions at MYB binding sites are lost, correlating with significant downregulation of target gene expression. When anchored to a gene desert region, the Myb transactivation domain (MybTA) is sufficient and necessary for nucleation of an enhancer-like region. Critically, long-range chromatin interactions are established up to 400 kb away from where MybTA is anchored. This results in the activation of transcription from distal cryptic elements, which is reduced or abolished in the presence of point mutations that disrupt its interaction with the co-activators P300/CBP. Together, these results indicate that MYB activity alone is sufficient to generate an enhancer, inducing transcription through precise enhancer-promoter crosstalk, and identify the MYB-P300/CBP axis as a therapeutically actionable vulnerability in enhancer-driven malignancies.
  • Journal article
    Ng HL, Burt R, Feldhahn N, 2026,

    BCR::ABL1-induced enhancer reprogramming uncovers hypersensitivity of Ph+ B-ALL cells to enhancer-targeting drugs

    , Advanced Science, ISSN: 2198-3844
  • Journal article
    Smith AL, Denny N, Chahrour C, Sharp K, Arachi M, Dopico-Fernandez AM, Elliott N, Harman JR, Jackson T, Geng H, Smith O, Bond J, Roberts I, Stam RW, Crump NT, Davies JOJ, Roy A, Milne TAet al., 2025,

    Enhancer heterogeneity in acute lymphoblastic leukemia drives differential gene expression in patients

    , BLOOD, Vol: 146, Pages: 2073-2087, ISSN: 0006-4971
  • Journal article
    Cross JW, Field L, Smith A, Neil E, Hamer L, Jackson T, Elliott N, Rice S, Crump N, Harman J, Ling RE, Wu Q, El Ouazzani N, Thomas R, Inglott S, Bartram J, Smith O, Bond J, Roberts I, Milne TA, Roy Aet al., 2025,

    PROM1/CD133 marks a proliferative stem cell-like population of blasts in KMT2A rearranged infant ALL

    , Blood Advances, Vol: 9, Pages: 4607-4613, ISSN: 2473-9537
  • Journal article
    Crump NT, Milne TA, 2025,

    Is enhancer function driven by protein–protein Interactions? From bacteria to leukemia

    , BioEssays, Vol: 47, ISSN: 0265-9247

    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.

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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