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

 

145ICTEM buildingHammersmith Campus

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Summary

 

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.


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


Collaborators

Prof. Stefan N. Constantinescu, Ludwig Institute for Cancer Research, Brussels, Belgium, 2011

Prof. Steven Johnsen, Georg August University GöttingenGZMB,Dept. of Molecular Oncology 37077 Göttingen, Germany, 2011

Prof. David E. Levy, New York University School of Medicine, Department of Pathology and New York University Cancer Institute, New York, NY 10016, USA, 2011

Prof. Anthony R. Green, Cambridge University, Cambridge,UK, 2009

Dr Ana Gamero, Temple University School of Medicine, Philadelphia, PA, USA, 2008

Prof. Michael J. Seckl, Imperial College London, 2005

Prof. Denise Sheer, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK, 2004

Dr Heike M Hermanns, Rudolf-Virchow-ZentrumDFG-Forschungszentrum für Experimentelle Biomedizin, Würzburg, Germany, 2003

Guest Lectures

Novel Players in the IFN-g Response, ISICR Meeting 2007, Oxford, UK, 2007

Transdução de Sinais: pura tagarelice celular?!?, Encontros Científicos de Análises Clínicas e Saúde Pública, Hospitais da Universidade de Coimbra, Coimbra, Portugal, 2007

Novel components of JAK/STAT signalling pathways identified using FACS-based siRNA screens, St George's, University of London, London, UK, 2006

Novel components of JAK/STAT signalling pathways identified using FACS-based siRNA screens, Instituto Gulbenkian de Ciência, Oeiras, Portugal, 2006

Analysis of Interferon-γ Signalling in Human Cells Through a Kinome-Wide siRNA Screen, ISICR Meeting 2005, Shanghai, China, 2005

Novel Signalling Requirements for the Class II HLA and Antiviral Responses to Interferon-γ, Keystone Symposia, Whistler, British Colombia, Canada, 2004

Of JAKs, STATs, Blind Watchmakers, Jeeps and Trains, Cancer Research UK Institutes Colloquium, Warwick, UK, 2003

Fas-Induced Apoptosis in Prostate Cancer Cell Lines, Universität Salzburg, Salzburg, Austria, 2000

Apoptosis - a Matter of Life and Death, Cancer Course 2001 - Cancer Research UK - London Research UK, London, UK, 2001

The Interferon-γ Response in Human Cells, Portuguese Young Scientists Meeting - IPATIMUP, Porto, Portugal, 2001

JAK/STAT Signalling in Response to IFN-γ and the IL-6 Family of Cytokines, Lerner Research Institute - Cleveland Clinic Foundation, Cleveland, Ohio, USA, 2002

JAK/STAT Signalling in Response to IFN-γ and the IL-6 Family of Cytokines, Mount Sinai School of Medicine, New York, USA, 2002

Apoptosis in Cancer, Cancer Course 2002 - Cancer Research UK - London Research Institute, London, UK., 2002

Of JAKs, STATs, Blind Watchmakers, Jeeps and Trains, Cancer Research UK Clinical Centre at Barts and The London, London, UK, 2004

Of JAKs, STATs, Blind Watchmakers, Jeeps and Trains, Institute of Child Health, London, UK, 2005

Novel components of JAK/STAT signalling pathways identified using FACS-based siRNA screens, University Hospital Aachen - Medical Faculty RWTH, Aachen, Germany, 2007

Research Student Supervision

Akan,D, The Role of DAPK2 in Interferon-gamma and Interleukin-6 Responses

Bonito,N, The role of MAPKs in the regulation of IL-6 responses

Carmo,CRD, The role of JAKs and STATs in Chemoresistance

Chakelam,S, Regulation of gp130 by ERKs

Demiray,B, The Role of JAKs and STATs in Chemoresistance

Giorgiou,M, The Role of DAPK2 in TRAIL-Induced Apoptosis

Hechler,J, The Role of ATM in Interferon responses

McLachlan,S, Investigating the role of JAks and STATs in FGF-2-induced chemoresistance

Misterek,M, The role of PI3K/AKT in IL-6 responses

Ngosa,R, The Role of DAPK2 in TRAIL-Induced Apoptosis

Papoutsoglou,P, Regulation of p21 and DNA damage responses by DAPK3

Pungaliya,A, The Role of JAKs and STATs in Chemoresistance

Robinson,D, The Role of JAKs and STATs in Chemoresistance

Santos,CTD, The role of ATM in IFNg

Schlegel,R, Regulation of TRAIL-induced Apoptosis