Auner Lab

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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.


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  • Journal article
    Parzych K, Saavedra Garcia P, Valbuena G, Alsadah HAH, Robinson M, Penfold L, Kuzeva D, Ruiz Tellez A, Loaiza S, Holzmann V, Caputo V, Johnson DC, Kaiser MF, Karadimitris A, Lam E, Chevet E, Feldhahn N, Keun H, Auner Het al., 2019,

    The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation

    , Oncogene, Vol: 38, Pages: 3216-3231, ISSN: 0950-9232

    VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. Its key role in governing protein homoeostasis has made VCP/p97 an appealing anticancer drug target. Here, we provide evidence that VCP/p97 acts as a regulator of cellular metabolism. We found that VCP/p97 was tied to multiple metabolic processes on the gene expression level in a diverse range of cancer cell lines and in patient-derived multiple myeloma cells. Cellular VCP/p97 dependency to maintain proteostasis was increased under conditions of glucose and glutamine limitation in a range of cancer cell lines from different tissues. Moreover, glutamine depletion led to increased VCP/p97 expression, whereas VCP/p97 inhibition perturbed metabolic processes and intracellular amino acid turnover. GCN2, an amino acid-sensing kinase, attenuated stress signalling and cell death triggered by VCP/p97 inhibition and nutrient shortages and modulated ERK activation, autophagy, and glycolytic metabolite turnover. Together, our data point to an interconnected role of VCP/p97 and GCN2 in maintaining cancer cell metabolic and protein homoeostasis.

  • Conference paper
    Yong K, Hinsley S, Sherratt D, Kendall J, Brown SR, Flanagan L, Williams C, Cavenagh J, Kaiser M, Rabin NK, Ramasamy K, Garg M, Auner HW, Hawkins SF, Bygrave C, De Tute RM, Morgan G, Davies FE, Owen RGet al., 2018,

    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

    , 60th Annual Meeting of the American-Society-of-Hematology (ASH), Publisher: AMER SOC HEMATOLOGY, ISSN: 0006-4971
  • Conference paper
    Morris C, Chabannon C, Masszi T, Russell N, Nahi H, Kobbe G, Krejci M, Auner H, Pohlreich D, Hayden P, Basak GW, Lenhoff S, Schaap N, van Biezen A, Knol C, Lacobelli S, Liu Q, Celanovic M, Garderet L, Kroeger Net al., 2018,

    Analysis of Data Collected in the European Group for Blood and Marrow Transplantation (EBMT) Registry on a Cohort of Myeloma Patients Receiving Plerixafor

    , 44th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: 761-762, ISSN: 0268-3369
  • Conference paper
    Garderet L, Sbianchi G, van der Werf S, Blaise D, Russell N, Auner H, Chevallier P, Nahi H, Remenyi P, Yakoub-Agha I, Isaksson C, Krejci M, Browne P, Lenhoff S, Soledad Gonzalez M, Parody Porras R, Wiktor-Jedrzejczak W, Wilson KMO, Trneny M, Poire X, Passweg J, Jantunen E, Jost E, Schoenland S, Kroeger Net al., 2018,

    Impact of induction regimen duration before autologous stem cell transplantation in myeloma

    , 44th Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: 650-651, ISSN: 0268-3369
  • Journal article
    Bringhen S, Milan A, Ferri C, Wäsch R, Gay F, Larocca A, Salvini M, Terpos E, Goldschmidt H, Cavo M, Petrucci MT, Ludwig H, Auner HW, Caers J, Gramatzki M, Boccadoro M, Einsele H, Sonneveld P, Engelhardt Met al., 2018,

    Cardiovascular adverse events in modern myeloma therapy - incidence and risks. A review from European Myeloma Network (EMN) and Italian Society of Arterial Hypertension (SIIA)

    , Haematologica, Vol: 103, Pages: 1422-1432, ISSN: 0390-6078

    Cardiovascular disease in myeloma patients may derive from factors unrelated to the disease (age, diabetes, dyslipidemia, obesity, prior cardiovascular diseases), related to the disease (cardiac AL-amyloidosis, hyperviscosity, high-output failure, arteriovenous shunting, anemia, renal dysfunction) and linked to antimyeloma treatment (anthracyclines, corticosteroids, alkylating agents, immunomodulatory drugs, proteasome inhibitors). An accurate knowledge of cardiovascular events, effective dose reductions, prevention and management of early and late cardiovascular side effects of chemotherapeutic agents are essential in current clinical practice. Myeloma experts are obliged to carefully balance drugs' efficacy and toxicity for each individual patient. This review summarizes current data and novel insights on cardiovascular adverse events of today's antimyeloma treatment, focusing on carfilzomib, which is the starting point to develop consensus recommendations on preventing and managing cardiovascular side effects in myeloma patients.

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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