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{Mateos:2020:10.1182/blood-2020-138391,
author = {Mateos, M and Gavriatopoulou, M and Facon, T and Auner, HW and Leleu, X and Hajek, R and Dimopoulos, MA and Delimpasi, S and Simonova, M and Spicka, I and Pour, L and Kryachok, I and Pylypenko, H and Doronin, VA and Usenko, G and Benjamin, R and Dolai, TK and Sinha, DK and Venner, CP and Garg, M and Stevens, DA and Quach, H and Jagannath, S and Moreau, P and Levy, M and Badros, AZ and Anderson, LD and Bahlis, NJ and Cavo, M and Chai, Y and Arazy, M and Shah, J and Shacham, S and Kauffman, MG and Richardson, PG and Grosicki, S},
doi = {10.1182/blood-2020-138391},
publisher = {AMER SOC HEMATOLOGY},
title = {Effect of Prior Treatment with Proteasome Inhibitors on the Efficacy and Safety of Once-Weekly Selinexor, Bortezomib, and Dexamethasone in Comparison with Twice-Weekly Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Subgroup Analysis from the Boston Study},
url = {http://dx.doi.org/10.1182/blood-2020-138391},
year = {2020}
}

RIS format (EndNote, RefMan)

TY  - CPAPER
AU - Mateos,M
AU - Gavriatopoulou,M
AU - Facon,T
AU - Auner,HW
AU - Leleu,X
AU - Hajek,R
AU - Dimopoulos,MA
AU - Delimpasi,S
AU - Simonova,M
AU - Spicka,I
AU - Pour,L
AU - Kryachok,I
AU - Pylypenko,H
AU - Doronin,VA
AU - Usenko,G
AU - Benjamin,R
AU - Dolai,TK
AU - Sinha,DK
AU - Venner,CP
AU - Garg,M
AU - Stevens,DA
AU - Quach,H
AU - Jagannath,S
AU - Moreau,P
AU - Levy,M
AU - Badros,AZ
AU - Anderson,LD
AU - Bahlis,NJ
AU - Cavo,M
AU - Chai,Y
AU - Arazy,M
AU - Shah,J
AU - Shacham,S
AU - Kauffman,MG
AU - Richardson,PG
AU - Grosicki,S
DO - 10.1182/blood-2020-138391
PB - AMER SOC HEMATOLOGY
PY - 2020///
SN - 0006-4971
TI - Effect of Prior Treatment with Proteasome Inhibitors on the Efficacy and Safety of Once-Weekly Selinexor, Bortezomib, and Dexamethasone in Comparison with Twice-Weekly Bortezomib and Dexamethasone in Relapsed or Refractory Multiple Myeloma: Subgroup Analysis from the Boston Study
UR - http://dx.doi.org/10.1182/blood-2020-138391
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000607547203050&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
ER -