Imperial College London

Dr Olivier E. Pardo

Faculty of MedicineDepartment of Surgery & Cancer

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2814o.pardo Website CV

 
 
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Location

 

131ICTEM buildingHammersmith Campus

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Summary

 

ONGOING RESEARCH

Factors involved in DRUG RESISTANCE IN CANCER

We have involved several S6 kinases in the regulation of drug resistance in a variety of cancer types, including lung, breast cancer and sarcoma. Our current work aims to identify the downstream targets involved in this effect, including translation and mRNA splicing factors. Our goal is to propose novel therapeutic targets for cancer treatment and increase our understanding of the molecular mechanisms leading to cancer cell survival.

Drug resistance

Proteins regulating the sensitivity of non small-cell lung cancer (NSCLC) to EGFR inhibitors

EGFR inhibitors, such as erlotinib and gefitinib, are new molecules used in the clinic to treat a proportion of lung cancer patients with EGFR activating mutations. However, these tumours ultimately become resistant to these compounds. We are part of a European FP7 consortium that aims both at understanding the various mechanisms responsible for this resistance and at designing novel therapeutic agents that may circumvent it.

NMR analysis of metabonomic changes accompanying resistance

cancer invasiveness and metastasis

We have performed a series of RNAi screens and identified novel regulators of lung and breast cancer cell migration and invasiveness. We are now in the process of investigating those proteins to understand their mechanism of action. In order to reach this goal, we have developed a series of in vitro and in vivo models to test novel agents that prevent cancer dissemination.

Studying Cell invasiveness

Compounds design/SCREENING/testing for our various targets

We are closely working with chemists, protein modellers and crystallographers to design novel compounds targeting our targets of interest. Through our industrial collaborations we also perform research using experimental compounds to assess their effect on lung cancer biology. Our clinical links enable us to take part in the design and running of clinical trials that aim at identifying novel therapies for lung cancer.

Modeling

Collaborators

Prof William Cookson, Imperial College-NHLI, Mesothelioma research funded by the Mesothelioma Centre, 2017

Dr Paul Huang, Institute for Cancer Research (ICR), Proteomics and phosphorpoteomics analysis of cancer cells in response to molecular perturbations. Also, substrate fishing for novel mammalian kinase isoforms., 2017

Dr Paul Ajun, Dundee Cell, Phosphoproteomics of gestational trophoblastic disease drug resistance, 2013 - 2017

Prof R Berkowitz, Dana Farber, Boston, USA, Gestational Trophoblastic Disease drug resistance, 2011 - 2014

Prof Mariano Barbacid, CNIO, Barcelona, Spain, role of S6K2 in lung cancer development using spontaneous murine lung cancer models, 2009 - 2014

Dr Alexandre Arcaro, University of Bern, Resistance of lung cancer cells to EGFR-TKIs and cell signalling, 2009 - 2014

Dr Jeff Smaill, Auckland Cancer Society Research Centre, Synthesis and testing of FGFR inhibitor prodrugs, 2010

Etienne Waelkens, Katholieke Universiteit Leuven-Belgium, Mass Spectrometry, 2010

Prof Johan Van Lint, Katholieke Universiteit Leuven-Leuven-Belgium, Mass Spectrometry, 2010

Dr Miguel Martins, MRC-Leicester-UK, Apoptosis Research, 2011

Dr Pieter Peeters, Johnson & Johnson-Beerse-Belgium, Drug Discovery, 2009

Dr Ines Royau, Janssen Pharmaceutica NV-Beerse-Belgium, Oncology Research, 2009

Dr Daniel Zicha, Cancer Research UK-London Research Institute-London-UK, Microscopy, 2006

Prof Julian Downward, Cancer Research UK-London Research Institute, Cell signalling in Cancer, 2006

Dr. Martin Holcik, CHEO Research Institute-University of Ottawa-Canada, Apoptosis Research, 2008

Dr Catherine Tralau-Stewart, Imperial College-London-UK, Drug Discovery, 2011

Dr Maruf Ali, Imperial College-London-UK, Crystallography, 2011

Prof Maggie Dallman, Imperial College-London-UK, Zebrafish research, 2009

Prof Ivan Gout, UCL-London-UK, Cell signalling, 2002

Prof Lin Guo, Wuhan University-Wuhan-China, Quantitative Mass Spectrometry, 2010

Prof Yulan Wang, Chinese Academy of Sciences-Wuhan-China, Metabonomics, 2011

Guest Lectures

Decreased glutathione synthesis mediates EGFR T790M-driven erlotinib resistance, Future Horizons in Lung Cancer, Royal Society of Medicine, London, 2016

Decreased glutathione synthesis mediates EGFR T790M-driven erlotinib resistance, World Cancer 2016 Conference, London, 2016

NRF2-mediated changes in glutathione metabolism mediate the resistance of EGFR-T790M mutant lung cancer cells to erlotinib, Personalized Medicine-2015, Valencia, 2015

FGF-2/S6K2 signalling promotes the nucleo-cytoplasmic shuttling of hnRNPA1 to increase cap-independent translation of BCL-XL and XIAP in cancer, Cancer Science-2015, Dubai, 2015

Metabonomics approach to identifying novel regulator of targeted therapy in lung cancer, Chinese Academy of Sciences, Wuhan, China, 2014

Changes in glutathione metabolism mediate the resistance of EGFRT790M mutant lung cancer cells to erlotinib., Symposium on metabonomics on translational medicine, Shanghai, China, 2014

RSKs in lung cancer invasion and metastasis, BIT 4th annual congress of Molecular and Cell Biology, Dalian, China, 2014

Studying cell invasiveness using complex 2D and 3D culture assays and zebrafish models., High-content screening conference, Sheffield University, Sheffield, UK, 2014

Changes in glutathione metabolism mediate the resistance of EGFRT790M mutant lung cancer cells to erlotinib, NCRI Conference, Liverpool, UK, 2013

Studying cell invasiveness using complex 2D and 3D culture assays and zebrafish models, SMI 3D culture Conference, London, 2013

Studying cell invasiveness using complex 2D and 3D culture assays and zebrafish models, Cell Based Assay Conference, London, 2013

FGF-2/S6K2 and hnRNPA1in the translational regulation of Bcl-XL and XIAP, Indian Association of Cancer Research, New Dehli, 2013

RSKs in lung and bladder cancer biology, 18th UK Academic Screening Group meeting. MRC-NIMR, London, UK, 2012

FGF-2/S6K2 and hnRNPA1in the translational regulation of Bcl-XL and XIAP, MRC, Leicester, UK, 2012

FGF-2/S6K2 and hnRNPA1in the translational regulation of Bcl-XL and XIAP, Genes and Cancer conference, Warwick, UK., 2012

Studying cell invasiveness using complex 3D culture assays and zebrafish models, Syngenta, Berlin, 2012

Towards a clinical trial ofHsp65 gene therapy for malignant mesothelioma, British Thoracic Society Winter Meeting, London, UK, 1998

Gene therapy for malignant mesothelioma with a heat shock protein 65 gene, ALA/ATS International Conference, Chicago, USA, 1998

Fibroblast growth factor-2 induces translational regulation of Bcl-XL and Bcl-2 via a MEK dependent pathway: correlation with resistance to etoposide induced apoptosis, BCRM, Leeds, UK, 2001

Role of the PKC/B-Raf/S6K2 multiprotein complex in FGF-2-mediated survival, Cancer Research UK, Charterhouse Square, London, UK, 2004

The use of RNAi-based kinome library screening in the identification of potential therapeutic targets for cancer, CNRS/INSERM Molecular Biology Department-Poitiers University, Poitiers, France, 2005

The FGFR inhibitor PD173074 blocks SCLC growth in vitro and in vivo, National Cancer Research Institute Meeting, Birmingham, UK, 2008

RSK family members in the regulation of lung cancer cell migration and invasion, St Bart’s and Queen Mary’s Medical School, London-UK, 2008

RNAi-mediated screen for regulators of cell migration and invasion in lung cancer, University of North Carolina, Chapel Hill, US, 2009

RNAi-mediated screen for regulators of cell migration and invasion in lung cancer, Jansen Pharmaceuticals, Beerse-Belgium, 2009

S6 kinases in the chemoresistance and metastasis of lung cancer, Wuhan School of Medicine, Wuhan, China, 2009

S6 kinase 2 and FGF-2 in lung cancer cell survival, Wuhan University, Wuhan, China, 2009

RNAi-mediated screen for regulators of cell migration and invasion in lung cancer, High-Throughput User Conference, Düsseldorf, Germany, 2009

S6 kinase 2 (S6K2) regulates cell survival through modulation of protein translation and mRNA splicing, RSM/BACR Meeting on MicroRNA and Translational Regulation in Cancer, London-UK, 2009

Using High Content Screening for the identification of novel modulators of cell migration and invasion in lung cancer, Cell-based Assay Conference, Cologne, Germany, 2010

High-throughput screening for the identification of novel modulators of cell migration, invasion and cytoskeletal organisation in lung cancer, Molecular Devices Technical Conference, Winersh Triangle-UK, 2010

Identification of novel modulators of lung cancer cell motility and invasiveness, RNAi & High Content Imaging Symposium 2011, Oxford-UK, 2011

S6 Kinases in Lung Cancer, Wuhan University, Wuhan-China, 2011

S6 Kinases in lung cancer biology, WIPM, Chinese Academy of Sciences, Wuhan, China, 2011

Research Staff

Roy,R

Research Student Supervision

Moonamale,D, RSK4 expression in cancer

Chiao Chin Gao,, RSK4 metabolomics in lung cancer

Huang,Y, FGF2/S6K2/hnRNPA1 pathway in sarcoma

Huang,Y, RSK4 drug screening

Huang,Y, RSK4 drug screening

Huang,Y, Metabolic signature and transforming potential associated with mycoplasma infection of lung epithelial cells

Gan,CC, Metabolic signature and transforming potential associated with mycoplasma infection of lung epithelial cells

Moonamale,D, Role of RSK4 in promoting metastasis, invasion and chemoresistance in model cancer cells.

Protopapa,L, The cell cycle pathway to methotrexate resistant choriocarcinoma

Lau,C, Investigating changes in EGFR signaling as a result of Erlotinib resistance

Veal,M, Investigating the role of p90 Ribosomal S6 kinase 4 in regulation of cellular energy metabolism in Lung Cancer cells

Huang,Y, The use of nanofiber/microfiber scaffolds for developing 3D cancer cell models

Zhang,A, FGF10 in the growth of breast cancer cells

Choo,J, Metothrexate resistance in gestational trophoblastic disease

Barnes,E, RPS6KC1 in lung cancer cel migration and invasion

Spain,G, RSK4 and metabolic changes in lung cancer

Sormendi,S, Biological function of S6K2-S3

Morcuende Ventura,V, RPS6KC1 in lung cancer

Liang,H-C, FGF10 in breast cancer

Alkaf,B, hnRNPA1 as an AKT substrate

Eckert,A, RSK4 drug discovery

Metcalf,G, RPS6KC1 in lung cancer metastasis

Chater,E, EGFR TKI resistance mechanisms and metabonomics

Georgiou,M, GTD drug resistance mechanisms

Li,M, S6K2 drug discovery

Walsh,D, RSK4 in lung cancer metabonomics

Chater,E, EGFR TKI resistance mechanisms and metabonomics

Xue,M, Identification of S6K2/PKCeps protein/protein interaction inhibitors

RIBEZZO,F, Studying the mechanisms of bone metastasis in prostate cancer

METCALF,G, The role of MARK4 in lung cancer invasiveness

GEORGIOU,M, Identification of small compound inhibitors of RSK4

Gubbins,J, Bone metastasis in Prostate Cancer

Lara,R, PhD project-siRNA screening for modulators of lung cancer cells motility and invasiveness

Rupniewska,E, PhD project: Targeting SRC family kinases in lung cancer

Munro,C, PhD project: Drugable genome-wide study of lung cancer cell local invasion towards the endothelium

Mufti,U, PhD project: Screening & Identification of Kinases Involved in Drug Resistance in Bladder Cancer

Cooney,D, Identification of small compound inhibitors of Ribosomal S6 Kinase 4 (RSK4)

Venmann,E, Cloning, expression, purification and crystallisation studies of RSK4 in parallel with a bioinformatics approach towards understanding the structure of RSK4

Kalu,S, Metabolic changes accompanying the overexpression of RSK4 in lung cancer

McLachlan,S, Elucidating the role of hnRNPA1 in lung cancer drug resistance

Akçakaya,P

Tsimon,M

Alcantara,D

Huang,P, Role of MARK4 in lung cancer cell metastasis, immune response and development in zebrafish

Castle,J, Using Zebrafish as a high-throughput drug screening tool in cancer therapeutics

Zhang,W, Elucidating the role of hnRNPA1 in lung cancer drug resistance

SARPER,M

Sum Yee,J, Modelling and Monitoring Cancer Cell Invasiveness using Zebrafish as an Animal Model

Majka,G