Auner Lab

Contact


Dr Holger Auner

  • CRUK Advanced Clinician Scientist
  • Clinical Reader in Molecular Haemato-Oncology

+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{Larocca:2018:10.1038/s41375-018-0142-9,
author = {Larocca, A and Dold, SM and Zweegman, S and Terpos, E and Waesch, R and D'Agostino, M and Scheubeck, S and Goldschmidt, H and Gay, F and Cavo, M and Ludwig, H and Straka, C and Bringhen, S and Auner, HW and Caers, J and Gramatzki, M and Offidani, M and Dimopoulos, MA and Einsele, H and Boccadoro, M and Sonneveld, P and Engelhardt, M},
doi = {10.1038/s41375-018-0142-9},
journal = {Leukemia},
pages = {1697--1712},
title = {Patient-centered practice in elderly myeloma patients: an overview and consensus from the European Myeloma Network (EMN)},
url = {http://dx.doi.org/10.1038/s41375-018-0142-9},
volume = {32},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Multiple myeloma is a disease typical of the elderly, and, because of the increase in life expectancy of the general population, its incidence is expected to grow in the future. Elderly patients represent a particular challenge due to their marked heterogeneity. Many new and highly effective drugs have been introduced in the last few years, and results from clinical trials are promising. Besides the availability of novel agents, a careful evaluation of elderly patients showed to be a key factor for the success of therapy. A geriatric assessment is a valid strategy to better stratify patients. In particular, different scores are available today to appropriately assess elderly patients and define their fitness/frailty status. The choice of treatment – transplantation, triplets, doublets, or reduced-dose therapies including novel agents – should depend on the patient’s fitness status (fit, intermediate-fit or frail). Second-generation novel agents have also been evaluated as salvage therapy in the elderly, and these new agents certainly represent a further step forward in the treatment armamentarium for elderly patients with multiple myeloma.
AU - Larocca,A
AU - Dold,SM
AU - Zweegman,S
AU - Terpos,E
AU - Waesch,R
AU - D'Agostino,M
AU - Scheubeck,S
AU - Goldschmidt,H
AU - Gay,F
AU - Cavo,M
AU - Ludwig,H
AU - Straka,C
AU - Bringhen,S
AU - Auner,HW
AU - Caers,J
AU - Gramatzki,M
AU - Offidani,M
AU - Dimopoulos,MA
AU - Einsele,H
AU - Boccadoro,M
AU - Sonneveld,P
AU - Engelhardt,M
DO - 10.1038/s41375-018-0142-9
EP - 1712
PY - 2018///
SN - 1476-5551
SP - 1697
TI - Patient-centered practice in elderly myeloma patients: an overview and consensus from the European Myeloma Network (EMN)
T2 - Leukemia
UR - http://dx.doi.org/10.1038/s41375-018-0142-9
UR - http://hdl.handle.net/10044/1/58981
VL - 32
ER -

Hugh and Josseline Langmuir Myeloma Centre