Imperial College London

Dr Ana P. Costa-Pereira

Faculty of MedicineDepartment of Surgery & Cancer

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2815a.costa-pereira Website

 
 
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Location

 

131ICTEM buildingHammersmith Campus

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Summary

 

Summary


QUALIFICATION AND PERSONAL HISTORY

  • January 2016: School of Medicine Head of BSc Medical Biosciences (BMB) & BSc Medical Biosciences with Management (BMBM)
  • April 2015: School of Medicine Head of BSc Programme Development
  • 2011: Promoted to Senior Lecturer 
  • 2005-2007: Visiting Scientist at The Francis Crick Institute (formerly Cancer Research UK - London Research Institute & also Imperial Cancer Research Fund)
  • October 2005: Joined Imperial College London as a Research Team Leader (Cytokines and Cancer Signalling Group) and Lecturer in the Department of Surgery and Cancer (formerly SORA), Faculty of Medicine
  • 1999-2005: Postdoctoral work at Cancer Research UK, London Research Institute (formerly Cancer Research UK - London Research Institute & also Imperial Cancer Research Fund) (Kerr Lab)
  • 1994-1999: PhD in Biochemistry, University College Cork, Ireland (Cotter Lab)

RESEARCH INTERESTS


Cytokines are small proteins produced by the immune system. They can have both beneficial and deleterious effects in cancer development and progression. These molecules are powerful and fast, and understanding how they elicit their biologic responses by activating Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) is of fundamental importance for our ability to manage a large number of cancers that either depend on JAK/STAT signalling or that have a strong inflammatory component. For the last 17 years, I have been dissecting signalling networks triggered in response to type I Interferons (IFN-α and IFN-βand type II (IFN-γ) and Interleukin-6-type cytokines (IL-6, OSM), and in the process challenged (successfully) the key paradigm explaining signalling specificity [Costa-Pereira et al. (2002). PNAS. 99: 8043]. Our work now focusses on devising ways to modulate cytokine signalling to develop more effective cancer therapies. This work, is complemented by our interest in other cytokines such as TRAIL and Fas (CD95), which signal through death receptors, thus triggering apoptosis. Current projects thus focus on:

• Regulation and organisation of cytokine signalling networks in tumour cells

• Tumour cell apoptosis signal transduction pathways

• Identification of novel targets for cancer therapy using the above knowledge

Key words: Cancer biology | signal transduction | apoptosis | cytokines | JAKs | STATs | NF-κB


MAIN RESEARCH OBJECTIVES

As a scientist, my most significant contribution to science has been the discovery that cytokine signalling specificity is not determined by the specific interaction of the ligand (postcard) and the receptor (postbox). That is to say that, within reason, the postcard and post box are irrelevant to fully deciphering the message written on the postcard, for it is the cellular environment with all its ‘molecular machines’ in place that effectively ‘seals the deal’. This is crucial for the output of many biological processes since our cells are never subjected to a single molecular signal and are in a state of permanent flux. Perhaps more importantly, or certainly more tangible to everyday life, is the fact that many molecular therapies using chemical inhibitors can fall foul of this.

My lab continues to utilise JAK/STAT signalling as a paradigm to unravel the molecular details of how signal transduction specificity is achieved and to translate this information into more effectively targeted cancer therapies. More specifically, we wish to:

  • unravel novel layers of regulation of signalling in response to IFNs (type I and II) and IL-6-type cytokines, with particular emphasis on the definition of the mechanism(s) of the mutational switch of an IL-6 response to an IFN-γ-like response in the absence of STAT3 - likely important in cancers where inflammation plays a major role;
  • establish the contribution of STATs, JAKs and other kinases (such as DAPKs, ERKs and AKTs) to molecular mechanisms that enable cancer cells to survive apoptosis triggered by diverse stimuli and/or evade the immune system;
  • utilise this information to devise alternative modalities of defeating drug resistance in the clinic.

To this end, we use/will use CRISPRs and RNAi technology as a starting point and classical molecular and cellular technics, combined with our expertise on high-throughput screening (HTS) using flow cytometry-based assays, as well as, good old fashioned antiviral assays.


SCIENTIFIC COLLABORATORS

  • Dr Heike M. Hermanns (University of Würzburg, Germany)
  • Prof. David E. Levy (NYU, USA)
  • Dr Ana Gamero (Temple University School of Medicine, USA)
  • Prof. Tony Green (Cambridge University, UK)
  • Prof. Steven Johnsen (University of Hamburg, Germany)
  • Prof. tim Palmer (Univ. Bradford, UK)
  • Dr Pat Eyers (Univ. Liverpool, UK)
  • Prof. Michael J. Seckl and Dr Olivier E. Pardo (Imperial College London, UK)
  • Prof. Simak Ali (Imperial College London, UK)

EDITORIAL BOARDS  


JAK-STAT (launched 2012) | PLoS ONE | Frontiers in Endocrinology


REVIEWER 


FUNDING

MRC | BBSRC | Pancreatic Cancer Research Fund (PCRF) | British Heart Foundation (BHF) | Chief Scientist Office Experimental and Translational Medicine Research Committee (Scotland) | Research Foundation Flanders (FWO) (Belgium)

EDITORIAL

J Cell Sci | J Molec Endocrinol | Gene Exp Pat | Molec and Cel Endocrinol | J Biol Chem | Gene Ther | PLoS One | J Eur Immunol | Cytokine | Eur J Cell Biol | FEBS J | FASEB | J Immunol Meth | JAK-STAT | Oncogene | Mol Cel Biol


MEMBERSHIP OF PROFESSIONAL BODIES

  • Fellow of the Higher Education Academy (FHEA) (awarded 2008)
  • International Society for Interferon and Cytokine Research (ISICR) 
  • British Association for Cancer Research (BACR) 
  • Fellow of the Higher Education Academy (HEA) 

INTERNAL COMMITTEES

  • Non-Professorial Member of the Senate
  • Imperial Cancer Research UK Centre/ ECMC Steering Committee | DoSC
  • Culture & People Committee (inc. Athena Swan) | DoSC
  • Postgraduate Education Committee (PGEC) |  DoSC
  • Undergraduate (UG) Medicine Board  | FoM
  • Curriculum Advisory Board (CAB) | FoM
  • Student Monitoring Group (SMG) Committee | FoM
  • Education Forum: BMB | FoM
  • Education Forum: BMS | FoM
  • Education Forum: MBBS Year 4 | FoM
  • BMB Student-Staff Liaison Committee (SSLC) | FoM (from Oct 2017)
  • BMS Student-Staff Liaison Committee (SSLC) | FoM
  • MBBS Student-Staff Liaison Committee (SSLC) | FoM

EXTERNAL COMMITTEES

  • Biochemical Society Theme Panel V (Signalling) Committee Member (2013-2016)
  • Member of the ISICR Standards Committee (2010-2012)
  • Member of the International Advisory Committee for the ISICR/ICS 2010 Meeting (Chicago, USA)
  • Member of the Jury of the 5th Edition of the Crioestaminal Award (2009, Portugal)
  • Member of the Organising Committee for the triple  joint meeting between the Society for Leukocyte Biology (LBS), ISICR and International Cytokine Society (ICS) (Oct 2009, Lisbon, Portugal)
  • Member of the Organising Committee for the BACR/ Royal Society of Medicine (RSM) Oncology Section conference in Cell Signalling and Novel Cancer Therapeutics (Nov 2007, London, UK)

OUTREACH

2015: Imperial College Festival - "What do scientists studying human diseases do?"

2013: Combination Dance - "Code" - scientific advisor

Publications

Journals

Rutherford C, Speirs C, Williams JJL, et al., 2016, Phosphorylation of Janus kinase 1 (JAK1) by AMP-activated protein kinase (AMPK) links energy sensing to anti-inflammatory signaling, Science Signaling, Vol:9, ISSN:1945-0877

Schlegel CR, Georgiou ML, Misterek MB, et al., 2015, DAPK2 regulates oxidative stress in cancer cells by preserving mitochondrial function, Cell Death & Disease, Vol:6, ISSN:2041-4889

Bonito NA, Drechsler J, Stoecker S, et al., 2014, Control of gp130 expression by the mitogen-activated protein kinase ERK2, Oncogene, Vol:33, ISSN:0950-9232, Pages:2255-2263

Costa-Pereira AP, 2014, Regulation of IL-6-type cytokine responses by MAPKs, Biochemical Society Transactions, Vol:42, ISSN:0300-5127, Pages:59-62

Schlegel CR, Fonseca A-V, Stoecker S, et al., 2014, DAPK2 is a novel modulator of TRAIL-induced apoptosis, Cell Death and Differentiation, Vol:21, ISSN:1350-9047, Pages:1780-1791

More Publications