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

@inproceedings{Yong:2018:10.1182/blood-2018-99-116624,
author = {Yong, K and Hinsley, S and Sherratt, D and Kendall, J and Brown, SR and Flanagan, L and Williams, C and Cavenagh, J and Kaiser, M and Rabin, NK and Ramasamy, K and Garg, M and Auner, HW and Hawkins, SF and Bygrave, C and De, Tute RM and Morgan, G and Davies, FE and Owen, RG},
doi = {10.1182/blood-2018-99-116624},
publisher = {AMER SOC HEMATOLOGY},
title = {Carfilzomib Versus Bortezomib in Combination with Cyclophosphamide and Dexamethasone for Treatment of First Relapse or Primary Refractory Multiple Myeloma (MM): Outcomes Based on Genetic Risk and Long Term Follow up of the Phase 2 Muk Five Study},
url = {http://dx.doi.org/10.1182/blood-2018-99-116624},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - CPAPER
AU - Yong,K
AU - Hinsley,S
AU - Sherratt,D
AU - Kendall,J
AU - Brown,SR
AU - Flanagan,L
AU - Williams,C
AU - Cavenagh,J
AU - Kaiser,M
AU - Rabin,NK
AU - Ramasamy,K
AU - Garg,M
AU - Auner,HW
AU - Hawkins,SF
AU - Bygrave,C
AU - De,Tute RM
AU - Morgan,G
AU - Davies,FE
AU - Owen,RG
DO - 10.1182/blood-2018-99-116624
PB - AMER SOC HEMATOLOGY
PY - 2018///
SN - 0006-4971
TI - Carfilzomib Versus Bortezomib in Combination with Cyclophosphamide and Dexamethasone for Treatment of First Relapse or Primary Refractory Multiple Myeloma (MM): Outcomes Based on Genetic Risk and Long Term Follow up of the Phase 2 Muk Five Study
UR - http://dx.doi.org/10.1182/blood-2018-99-116624
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000454837601015&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
ER -