Auner Lab

Contact


Dr Holger Auner

  • Clinical Senior Lecturer and Honorary Consultant in Haematology
  • Head of Translational Research at the Centre
  • Group Leader - Cancer Cell Protein Metabolism

+44 (0)20 3313 4017
holger.auner04@imperial.ac.uk

Areas of research


Proteotoxic stress and metabolism

Myeloma cells are characterised by a unique sensitivity to inhibitors of the proteasome, which is responsible for the controlled degradation of most cellular proteins that have become damaged or are otherwise unwanted. Nevertheless, resistance to proteasome inhibitors occurs in essentially all patients to varying degrees. Accumulation of misfolded proteins in the endoplasmic reticulum (ER), which triggers proteotoxic ‘ER stress’, is widely believed to be the main mechanism of action of proteasome inhibitors. However, data from our lab and other research groups suggest complex interactions between proteasomal protein degradation and multiple metabolic processes. Our aim is to find metabolic and proteostatic vulnerabilities that we can exploit therapeutically.


Tissue biophysics in myeloma biology

Several important aspects of cancer cell biology are influenced by mechanical cues from the surrounding tissue. In particular, mechanical interactions and matrix remodelling have been shown to govern cancer cell metabolism. Tissue stiffness also impacts on normal haematopoiesis, and mechanical cues are known to modulate therapeutic responses. Moreover, we have shown that proteostasis-targeting drugs can alter tissue physical properties. We aim to understand how tissue stiffness and nutrient availability act together to rewire metabolic networks and regulate drug responses in myeloma.


Citation

BibTex format

@article{Graziani:2020:10.1080/10428194.2019.1695051,
author = {Graziani, G and Herget, G and Ihorst, G and Zeissig, M and Chaidos, A and Auner, H and Duyster, J and Waesch, R and Engelhardt, M},
doi = {10.1080/10428194.2019.1695051},
journal = {Leukemia and Lymphoma},
pages = {875--886},
title = {Time from first symptom onset to the final diagnosis of Multiple Myeloma (MM) - possible risks and future solutions: retrospective and prospective ‘Deutsche Studiengruppe MM’ (DSMM) and ‘European Myeloma Network’ (EMN) analysis},
url = {http://dx.doi.org/10.1080/10428194.2019.1695051},
volume = {61},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Multiple Myeloma (MM) often presents with unspecific symptoms and is challenging to diagnose. We performed this DSMM/EMN-analysis via test-(retro-) and validation (prospective) study to determine the time interval from the onset of first symptoms to the diagnosis of MM. The retrospective and prospective analyses were performed in 101 and 176 patients, respectively. The median time from first symptoms to the MM diagnosis in both cohorts was 4 and 6 months, respectively. Frequencies of MM-related pathologic bone fractures, renal and infectious complications at diagnosis occurred in 41%, 35% and 16% of patients, respectively. Our MM-questionnaire determined that 39% of patients were dissatisfied with the diagnostic process. PFS and OS proved insignificantly different with shorter (≤6) and longer (>6 months) latency periods. In conclusion, our in depth studies demonstrate that delays in diagnosis do not decrease PFS or OS, but induce MM-related complications and influence patients' satisfaction with their medical care.
AU - Graziani,G
AU - Herget,G
AU - Ihorst,G
AU - Zeissig,M
AU - Chaidos,A
AU - Auner,H
AU - Duyster,J
AU - Waesch,R
AU - Engelhardt,M
DO - 10.1080/10428194.2019.1695051
EP - 886
PY - 2020///
SN - 1026-8022
SP - 875
TI - Time from first symptom onset to the final diagnosis of Multiple Myeloma (MM) - possible risks and future solutions: retrospective and prospective ‘Deutsche Studiengruppe MM’ (DSMM) and ‘European Myeloma Network’ (EMN) analysis
T2 - Leukemia and Lymphoma
UR - http://dx.doi.org/10.1080/10428194.2019.1695051
UR - https://www.tandfonline.com/doi/full/10.1080/10428194.2019.1695051
UR - http://hdl.handle.net/10044/1/75220
VL - 61
ER -