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{Morris:2020:10.1038/s41409-019-0676-0,
author = {Morris, C and Chabannon, C and Masszi, T and Russell, N and Nahi, H and Kobbe, G and Krejci, M and Auner, H and Pohlreich, D and Hayden, P and Basak, GW and Lenhoff, S and Schaap, N and van, Biezen A and Knol, C and Iacobelli, S and Liu, Q and Celanovic, M and Garderet, L and Kröger, N},
doi = {10.1038/s41409-019-0676-0},
journal = {Bone Marrow Transplantation},
pages = {356--366},
title = {Results from a multi-center, non-interventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor},
url = {http://dx.doi.org/10.1038/s41409-019-0676-0},
volume = {55},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Plerixafor plus granulocyte-colony stimulating factor (G-CSF) enhances the mobilization of haematopoietic stem cells (HSCs) for collection and subsequent autologous haematopoietic stem cell transplantation (HSCT) in patients with multiple myeloma (MM).This international, multicenter, non-interventional registry study (NCT01362972), evaluated long-term outcomes for MM patients who received plerixafor versus other mobilization regimens. The comparisons were: G-CSF+plerixafor (G-CSF+P) versus G-CSF-; G-CSF+P versus G-CSF+chemotherapy (G-CSF+C); and G-CSF+P+C versus G-CSF+C. Propensity score matching was used to balance groups. Primary outcome measures were progression free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR) after transplantation. After propensity matching, 77 versus 41 patients in the G-CSF+P versus G-CSF cohorts, 129 versus 129 in the G-CSF+P versus G-CSF+C cohort and 117 versus 117 in the G-CSF+P+C versus G-CSF+C cohort, were matched, respectively. Propensity score matching resulted in a smaller sample size and imbalances were not completely overcome. For both PFS and OS, the upper limits of the hazard ratio 95% confidence intervals exceeded pre-specified boundaries; non-inferiority was not demonstrated. CIR rates were higher in the plerixafor cohorts. G-CSF+P remains an option for the mobilization of HSCs in poor-mobilizers with MM with no substantial differences in PFS, OS and CIR in comparison with other regimens.
AU - Morris,C
AU - Chabannon,C
AU - Masszi,T
AU - Russell,N
AU - Nahi,H
AU - Kobbe,G
AU - Krejci,M
AU - Auner,H
AU - Pohlreich,D
AU - Hayden,P
AU - Basak,GW
AU - Lenhoff,S
AU - Schaap,N
AU - van,Biezen A
AU - Knol,C
AU - Iacobelli,S
AU - Liu,Q
AU - Celanovic,M
AU - Garderet,L
AU - Kröger,N
DO - 10.1038/s41409-019-0676-0
EP - 366
PY - 2020///
SN - 1476-5365
SP - 356
TI - Results from a multi-center, non-interventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor
T2 - Bone Marrow Transplantation
UR - http://dx.doi.org/10.1038/s41409-019-0676-0
UR - https://www.nature.com/articles/s41409-019-0676-0
UR - http://hdl.handle.net/10044/1/71932
VL - 55
ER -