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{Zhou:2026:10.3324/haematol.2026.s2.14067,
author = {Zhou, J and Crump, NT and Román-Trufero, M and Auner, HW},
doi = {10.3324/haematol.2026.s2.14067},
journal = {Haematologica},
pages = {1--1},
title = {TIME-RESOLVED MULTI-LAYERED PROFILING IDENTIFIES RESOLUTION OF RIBOSOME COLLISIONS AND TRANSLATIONAL RECOVERY AS MECHANISMS CONTRIBUTING TO PROTEASOME INHIBITOR RESISTANCE},
url = {http://dx.doi.org/10.3324/haematol.2026.s2.14067},
volume = {111},
year = {2026}
}
TY - JOUR
AB - Background. Multiple myeloma (MM) is characterised by a high dependence on intracellular protein homeostasis (proteostasis), a vulnerability exploited therapeutically by proteasome inhibitors (PIs) that disrupt protein degradation and induce proteotoxic stress. PIs have significantly improved clinical outcomes, but molecular mechanisms underlying adaptive resistance of MM cells to PI-induced stress remain incompletely understood. Ribosome collisions (RCs) are events that occur during compromised mRNA translation when ribosomes slow or pause, causing trailing ribosomes to physically collide. This triggers translational stress signaling aimed at resolving RCs and restoring homeostatic protein synthesis. Whether proteasome inhibition induces RCs in MM cells and whether RC resolution mechanisms contribute to adaptive PI resistance remains unknown. Methods. MM cell lines were exposed to a short pulse of carfilzomib (Cfz) to mimic clinical pharmacokinetics and followed by multi-omic analyses. RNA-seq and ribosome profiling (ribo-seq) were performed at 4h (acute stress), 24-48h (early recovery) and 6 days (late recovery) post-treatment. Global protein synthesis was assessed by puromycin incorporation, intracellular amino acid levels were quantified by targeted metabolomics (LC-MS/MS), and changes in gene and protein expression and phosphorylation were analysed by qRT-PCR and immunoblotting. Results. Cfz rapidly induced RCs, activation of the ZAKalpha-P38 initiated ribotoxic stress response (RSR), reduction of amino acids, activation of the integrated stress response (ISR) and suppression of global protein synthesis. Despite this translational repression, ribo-seq revealed selective enhancement of translation of proteasome subunits and stress-response genes in line with a “proteasome bounce-back” mechanism. During the 24h-48h period, RCs were resolved and both RSR and ISR signalling progressively decreased. Simultaneously, global protein synthesis recovered and
AU - Zhou,J
AU - Crump,NT
AU - Román-Trufero,M
AU - Auner,HW
DO - 10.3324/haematol.2026.s2.14067
EP - 1
PY - 2026///
SN - 0390-6078
SP - 1
TI - TIME-RESOLVED MULTI-LAYERED PROFILING IDENTIFIES RESOLUTION OF RIBOSOME COLLISIONS AND TRANSLATIONAL RECOVERY AS MECHANISMS CONTRIBUTING TO PROTEASOME INHIBITOR RESISTANCE
T2 - Haematologica
UR - http://dx.doi.org/10.3324/haematol.2026.s2.14067
VL - 111
ER -