Professor Thorsten Hagemann

MD PhD
Centre: Cancer and Inflammation
Fellowships:
MRC Clinician Scientist
Job Title: Professor of Pancreatic Cancer Medicine (HCC)
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Research Interests


Dr Thorsten Hagemann's main research themes are in: Cancer Immunology, Metastasis and Invasion, Ovarian Cancer, Pancreatic Cancer and Tumour Angiogenesis


Blood-forming stem cells follow one of two different development pathways and differentiate into either lymphoid (T or B cells) or myeloid (all other white blood cells) cells. My research group is focused on understanding the molecular and cellular basis for the functional heterogeneity of the myeloid cell lineage. We employ molecular biology approaches to understand how innate immunity may contribute to human health and disease, particularly cancer.

We investigate the hypothesis that targeting specific signalling pathways in macrophages can alter immunity. This will provide fundamental information on the role of these signalling pathways in innate immunity, immune tolerance and innate immune function in cancer, chronic disease, transplantation or ageing.

These mechanisms may be deregulated and could represent potential therapeutic targets to modify innate immune responses in cancer. The molecules and mechanisms identified by those studies are then examined for human counterparts that may teach us about pathogenesis, and provide new tools for application in clinical trials that we undertake.

Although each researcher in the laboratory pursues a clearly defined project, great emphasis is placed on the synergies that can be realised through small teams of researchers working together on the following areas.

1. Regulation of myeloid cell differentiation and polarisation
Depending on the anatomical location and physiological context, tissue macrophages may display both pro- and anti-inflammatory phenotypes. Macrophages contribute to tissue remodelling, host defence in innate and adaptive immunity and are key to many disease processes. A clearer understanding of what determines the spectrum of innate, classical, alternative, and other activation phenotypes in macrophage populations are needed for selective targeting of pathogenic pathways.

2. Regulation of myeloid stress-surveillance in men and mice
The focus here is on the role of the mTOR pathway in regulating ‘alternative activation’ of macrophages in response to environmental stress (tumour development, infection, transplantation, ageing) and its contribution to the decline in innate immunity.

3. Innate immune responses to therapy induced tissue damage
Myeloid cell recruitment occurs in sites of tissue damage caused by chemo- or radiotherapy. Polarised myeloid cells promote the “wounding” of the tumour – providing continuous support for tumour re-growth and progression. This distinct myeloid stress response is particularly relevant to novel therapies targeting the microenvironment.

4. Tumour immunology in model systems and the clinic
We study the spontaneous development of kras/p53 driven pancreatic cancers and the response of the innate immune system to the early and late stages of disease development. Functional and phenotypic changes of the myeloid subsets correlate with the human innate immune system.

Profile

  • 2009 - present: Clinical Senior Lecturer, Honorary Consultant in Medical Oncology; Barts Cancer Institute
  • 2007 - Present: MRC Clinician Scientist Fellowship; Barts Cancer Institute
  • 2007 - 2009: Clinical Lecture, Barts Cancer Institute
  • 2009: GMC Specialist Register Medical Oncology
  • 2008: GMC Specialist Register Haematology and Internal Medicine
  • 2007 - 2009: Specialist Registrar in Medical Oncology, St Bartholomew’s Hospital London
  • 2005 - 2007: Clinical Research Fellow, Translational Oncology, Barts Cancer Institute, St Bartholomew’s Hospital, London
  • 1999 - 2005: Specialist Registrar, Centre for Internal Medicine, Department for Haematology and Oncology, University of Göttingen, Germany.

Funding

2013 - 2016 Pancreatic Cancer Research Fund Defining the role of regulatory B cells in pancreatic cancer
£177,368
2011-2017 Cancer Research UK Senior Cancer Research Fellowship - Mammalian target of rapamycin (mTOR) regulates innate immune function in the tumour microenvironment
£2.2m
2013 Cancer Research Technology Ltd Antibody generation against predefined targets
£88,000
2013 Medimmune Ltd Pancreatitis Study
£18,711
2013 Commission of the European Community Tumor Infiltrating Myeloid Cell Compartment (TIMCC)
£430,060
2013 Synthon B.V Pharmacokinetic study in carboxylesterase 1 Deficient C35B16 mice
£45,000
2013 Royal Embassy of Saudia Arabia Tumor Immunology Project
£57,000
2013 Nine-tz Healthcare Ventures Unrestricted Education Grant
£35,000
2012 Cancer Research UK Phase I dose escalatiion trial of HDAC inhibitor
£99,375
2012 AGE UK RESEARCH INTO AGEING FUND Improving immune defence in ageing individuals
£77,250
2012 Gilead Sciences Ltd Testing therapeutic potential of Gilead compound GS-9820
£200,427
2011-2017

Cancer Research UK

Training Fellowship - Mammalian target of rapamycin (mTOR)
£954,322
2011 Cancer Research UK Training Studentship - Mammalian target of rapamycin (mTOR)
£147,204
2011 Barts And The London Charity Salary
£74,050
2011 Opsona Therapeutics Ltd Gemcitabine experiments
£135,149
2011 Medimmune Ltd Comprehensive Analaysis of the Macrophage Phenotype-Studentship
£130,654
2011 - 2013

Pancreatic Cancer Research Fund

Enhancing oncolytic adenovirus efficacy in pancreatic cancer by switching tumour-associated macrophages
£150,000
2010 Immodulon Therapeutics Evaluating potential survival benefit of IMM101 or MVAC001 in a genetic model of pancreatic cancer with and without Gemcitabine treatment
£283,987
2009 - 2013 Medical Research Council, UK Case Industrial Collaborative Studentship (with AstraZeneca): IKK2 Inhibitors in Cancer
£83,910
2009 Barts And The London Charity Mouse Model of Ovarian Cancer
£8,000
2009 Cancer Research UK Inflammation via Paracine TNF-alpha
£226,210
2009 AstraZeneca UK Limited Industrial Collaborative Studentship 2009/10
£56,820
2009 AstraZeneca UK Limited Therapeutic potential of TLR7 agonists with or without the combination of conventional chemotherapy
£43,347
2008

Medical Research Council, UK

DTG 2008/09
£71,700
2008 Baxter Innovations Gmbh

Anti-MIF strategies for Therapeutic Use
£503,673

 

Key Publications

Neyen C, Plüddemann A, Mukhopadhyay S, Maniati E, Bossard M, Gordon S, Hagemann T. Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer. J Immunol, 2013. PMID: 23447685

Maniati E, Bossard M, Cook N, Candido JB, Emami-Shahri N, Nedospasov SA, Balkwill FR, Tuveson DA, Hagemann T. Crosstalk between the canonical NF-κB and Notch signaling pathways inhibits Pparγ expression and promotes pancreatic cancer progression in mice.  J Clin Invest, 2011. PMID: 22056382

The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. Charles KA, Kulbe H, Soper R, Escorcio-Correia M, Lawrence T, Schulthesis A, Chakravarty P, Thompson RG, Kollias G, Smyth JF, Balkwill F, Hagemann T. J Clin Invest, 2009. PMID: 19741298

"Re-educating" tumor-associated macrophages by targeting NFκB signalling. Hagemann T, Lawrence T, McNeish I, Kulbe H, Thompson RG, Charles KA, Robinson SC, Balkwill FR. J Exp Med, 2008. PMID: 18490490


Further Publications

For additional publications, please click here.

Research Group

Tumour Microenvironment Group

  • Eleni Maniati, PhD (postdoc)
  • Raphael Zollinger, PhD (postdoc)
  • Maud Bossard (PhD student)
  • Juliana Candido (PhD student)
  • Nia Emami-Shahr (PhD student)
  • Jenny Cook, (PhD student)
  • Cristina Ghirelli, PhD (postdoc)
  • Fiona McCarthy(Clinical Research Fellow)
  • Rozita Roshani (research assistant)
  • TBA {postdoc} To be advertised here shortly
  • TBA (research technician} To be advertised here shortly
  • TBA {PhD student from 1st Oct 2012} To be advertised here shortly

External Activities

Member of CIMT Communications Association for Cancer Immunotherapy.

News

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02 November 2011
Dr Thorsten Hagemann judges the
MedImmune's  European Cancer Research Research Abstract Competition.

→Click here for more information.