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Dr Klaus Pors

PositionSenior Lecturer in Chemical Biology & YCR Group Leader
DepartmentInstitute of Cancer Therapeutics
Telephone+44 (0) 1274 236482
EmailK.Pors1@bradford.ac.uk
Twitter@ArtDrugDiscover
LinkedInVisit my LinkedIn profile

Research Interests (key words only)

Chemical tools and novel therapeutic agents; Cancer biomarkers; Hypoxia & tumour microenvironment; Molecular fluorescent probes; Aldehyde dehydrogenase; Aldo-keto reductases; Cytochromes P450

PhD Supervision

PhD students

Ms Daniela Presa: Interrogation of CYP2W1 in head and neck cancer
Joint supervision with Prof Jim McCaul (Royal Marsden Hospital)

Ms Maria Sadiq: Interrogation of ALDHs in prostate cancer
Joint supervision with Prof Roger M. Phillips (University of Huddersfield) and Prof Norman J. Maitland (University of York)

Mr Ali Ibrahim: Design of chemical tools to probe aldehyde dehydrogenase pathways
Joint supervision with Prof Laurence H. Patterson (ICT)

Overseas placement students

Ms Teresa Folino: Synthesis of tetrahydroisoquinolines to probe AKR1C3 activity
Undergraduate student from University of Turin, Italy (2017)

Ms Eleonora Quaranta: Evaluation of NSAID-derived compounds with potential to target AKR1C3 prostate cancer
Undergraduate student from University of Turin, Italy (2017)

Mr Remi Legrand: Synthesis of molecular trigger groups
Undergraduate student from ESCOM Compiegene, France (2016-17)

Teaching and Supervisory Responsibilities

Administrative Responsibilities

  • Module Leader: Case Studies in Cancer Drug Discovery (2009 – present)
  • Module Leader: Molecular Basis of Cancer and Cancer Therapy (2014 – present)
  • Co-ordinator of External Undergraduate Research Training Placements (2007 – present)
  • Co-ordinator of GCSE and A-level student placements (2013 – present)

Study History

  • PhD, UCL School of Pharmacy, London, UK (2002)
  • BEng Chemical Engineering, University of Southern Denmark, Odense, Denmark (1998)

Professional History

 

Professional Activities

  • External Examiner, BSc Biopharmaceutical Science, University of Sunderland (2015-)
  • External Examiner, MSc in Drug Design and Discovery, University of Salford (2015-)
  • Guest Lecturer, "Chemistry in Drug Discovery" (2013 – present), Ecole Superieure de Chimie Organique et Minerale (ESCOM, Paris, France)
  • Guest Lecturer, in "Cancer Drug Discovery" (2013 – present), The Department of Science and Drug Technologies, University of Torino (Italy)
  • Editor, CICR Editorial Board (AACR, 2012-2016); Past Editor (2017)
  • Member, CICR Nominating Committee (2013-2014)
  • Editorial Board member, Scientific Reports (2016-)
  • Editorial Board member, Journal of Cancer Metastasis and Treatment (2014)
  • British Association for Cancer Research (BACR), past executive committee member (2008-2011)
  • BACR Membership Services & Financial Sub-Committee, past executive member (2008-2011)
  • Young Chemists in Cancer Research (AACR), past CICR committee member (2009-2011)
  • Member of UK-China Advanced Materials Research Institute (AMRI) (2012-present)
  • Elected member of the EPSRC peer review college (2016-)
  • Elected member of the British Council, Newton Schemes (2016-)
  • Ad-hoc grant reviewer for research councils and charities (MRC, AICR, Breast Cancer Now)
  • Ad-hoc manuscript reviewer (e.g. JACS, J Med Chem, ACS Med Chem Letters, BMCL, Curr Cancer Drug Targets)

Research Areas

Research in the Pors group is focussed on research at the interface between chemistry and biology. Traditional approaches to drug discovery such as target oriented synthesis and medicinal chemistry are used to develop focussed libraries of small molecules that are entirely new chemical entities or re-engineered versions of natural products. In addition, we use diversity-oriented synthesis to generate collections of small molecules of structural diverse architecture, which can be used to probe new chemical space or known biological pathways that are not well understood.

In the context of cancer, small molecules are designed to (i) exploit enzymatic and/or physiological conditions found unique to the tumour microenvironment or (ii) circumvent or exploit resistance mechanisms present in malignant tissue. As an extension of the latter, we are actively engaged in understanding how epigenetic therapy may affect the regulation and expression of drug metabolising enzymes (pharmacoepigenetics).

In addition, we are also interested in developing molecular fluorescent probes that can be used to stain fixed or live cells with wide applications in routine and research laboratories utilising flow cytometry and fluorescence imaging methods.

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Research in the Pors group is currently being funded by Yorkshire Cancer Research and Prostate Cancer UK.

Research Group

YCR programme team:
Dr Goreti Ribeiro Morais (2014-19)
Dr Xiaoxiao Guo (2015-19)
Dr Marcella Sini (2015-19)

Dr Jordi Morral, Honorary Research Fellow

Research Collaborations

Probing Cytochromes P450 in Cancer

  • Prof Magnus Ingelman-Sundberg, Dept. of Physiology & Pharmacology, Karolinska Institute, Sweden
  • Prof Emily E. Scott, Department of Medicinal Chemistry, University of Kansas, USA
  • Prof Jacques Robert, Institute of Bergonié, University of Bordeaux, France
  • Prof Mark Searcey, School of Pharmacy, University of East Anglia, UK
  • Prof Colin W. Fishwick, School of Chemistry, University of Leeds, UK

Probing Aldehyde Dehydrogenases in Cancer

  • Prof Jan S. Moreb, Department of Medicine, University of Florida, USA
  • Prof Norman J. Maitland, Department of Biology, University of York

Interrogation of DNA-drug Binding & Cellular Damage Responses

  • Prof John Hartley, UCL Cancer Institute, London, UK

Development of Molecular Fluorescent Probes

  • Prof Rachel Errington, Institute of Cancer and Genetics, School of Medicine, Cardiff University, UK
  • Prof Paul J. Smith, Institute of Cancer and Genetics, School of Medicine, Cardiff University, UK

Tumour Microenvironment & Chemical Probe Discovery

  • Prof Hongjuan Cui, State Key Laboratory, Southwest University, Chongqing, China
  • Prof Lijuan Chen, State Key Laboratory, Sichuan University, Chengdu, China
  • Dr Heiko Wurdak, Leeds Institute of Cancer and Pathology, Leeds University, UK
  • Profs Donatella Boschi & Marco Lolli, Department of Science and Drug Technologies, University of Torino, Italy

Publications

  • Wright EP, Day HA, Ibrahim AM, Kumar J, Boswell LJ, Huguin C, Stevenson CE, Pors K*, Waller ZA*. Mitoxantrone and Analogues Bind and Stabilize i-Motif Forming DNA Sequences. Sci Rep. 2016 Dec 22;6:39456. doi: 10.1038/srep39456. PubMed PMID: 28004744. *Joint corresponding authors
  • Elkashef SM, Allison SJ, Sadiq M, Basheer HA, Ribeiro Morais G, Loadman PM, Pors K, Falconer RA. Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment. Sci Rep. 2016 Sep 9;6:33026. doi:10.1038/srep33026. PubMed PMID: 27611649.
  • Sellars JD, Skipsey M, Sadr-Ul-Shaheed, Gravell S, Abumansour H, Kashtl G, Irfan J, Khot M, Pors K, Patterson LH, Sutton CW. Rational Development of Novel Activity Probes for the Analysis of Human Cytochromes P450. ChemMedChem. 2016 Jun 6;11(11):1122-8. doi: 10.1002/cmdc.201600134. [Epub ahead of print] PubMed PMID: 27154431.
  • Lolli M, Narramore S, Fishwick CWG and Pors K. Refining the chemical toolbox to be fit for educational and practical purpose for drug discovery in the 21st Century. Drug Discovery Today. May 2015, doi: 10.1016/j.drudis.2015.04.010. [Epub ahead of print]
  • Vinader V, Sadiq M, Sutherland M, Huang M, Loadman PM, Elsalem L, Shnyder SD, Cui H, Afarinkia K, Searcey M, Patterson LH and Pors K. Probing cytochrome P450-mediated activation with a truncated azinomycin analogue. MedChemComm, 2015, 6, 187 - 191
  • Pors K* and Moreb J*. Aldehyde dehydrogenases in cancer: an opportunity for biomarker and drug development? Drug Discovery Today. 2014 Dec;19(12):1953-63. *Joint corresponding authors
  • Thomas A, Perry T, Berhane S, Oldreive C, Zlatanou A, Williams LR, Weston VJ, Stankovic T, Kearns P, Pors K*, Grand RJ*, Stewart GS*. The dual-acting chemotherapeutic agent Alchemix induces cell death independently of ATM and p53. Oncogene. 2014 Aug 18;0. doi: 10.1038/onc.2014.266. [Epub ahead of print]. *Joint corresponding authors
  • Liu X, Hu L, Ge G, Yang B, Ning J, Sun S, Yang L, Pors K, Gu J. Quantitative analysis of cytochrome P450 isoforms in human liver microsomes by the combination of proteomics and chemical probe-based assay. Proteomics. 2014 Aug;14(16):1943-51. doi: 10.1002/pmic.201400025. Epub 2014 Jul 14
  • Stenstedt K, Travica S, Guo J, Barragan I, Pors K, Patterson L, Edler D, Mkrtchian S, Johansson I, Ingelman-Sundberg M. CYP2W1 polymorphism: functional aspects and relation to risk for colorectal cancer. Pharmacogenomics. 2013 Oct;14(13):1615-22. doi: 10.2217/pgs.13.136
  • Sheldrake HM, Travica S, Johansson I, Loadman PM, Sutherland M, Elsalem L, Illingworth N, Cresswell AJ, Reuillon T, Shnyder SD, Mkrtchian S, Searcey M, Ingelman-Sundberg M, Patterson LH, Pors K. Re-engineering of the duocarmycin structural architecture enables bioprecursor development targeting CYP1A1 and CYP2W1 for biological activity. J Med Chem. 2013 Aug 8;56(15):6273-7. doi: 10.1021/jm4000209. Epub 2013 Jul 26
  • Travica S*, Pors K*, Loadman PM, Shnyder SD, Johansson I, Alandas MN, Sheldrake HM, Mkrtchian S, Patterson LH, Ingelman-Sundberg M. Colon cancer-specific cytochrome P450 2W1 converts duocarmycin analogues into potent tumor cytotoxins. Clin Cancer Res. 2013 Jun 1;19(11):2952-61. doi: 10.1158/1078-0432.CCR-13-0238. Epub 2013 Apr 15. *Joint first authors
  • Cosentino L, Redondo-Horcajo M, Zhao Y, Santos AR, Chowdury KF, Vinader V, Abdallah QM, Abdel-Rahman H, Fournier-Dit-Chabert J, Shnyder SD, Loadman PM, Fang WS, Díaz JF, Barasoain I, Burns PA, Pors K. Synthesis and biological evaluation of colchicine B-ring analogues tethered with halogenated benzyl moieties. J Med Chem. 2012 Dec 27;55(24):11062-6. doi: 10.1021/jm301151t. Epub 2012 Dec 7
  • Smith PJ, Wiltshire M, Chappell SC, Cosentino L, Burns PA, Pors K, Errington RJ. Kinetic analysis of intracellular Hoechst 33342--DNA interactions by flow cytometry: misinterpretation of side population status? Cytometry A. 2013 Jan;83(1):161-9. doi: 10.1002/cyto.a.22224. Epub 2012 Nov 7
  • Fournier-Dit-Chabert J, Vinader V, Santos AR, Redondo-Horcajo M, Dreneau A, Basak R, Cosentino L, Marston G, Abdel-Rahman H, Loadman PM, Shnyder SD, Díaz JF, Barasoain I, Falconer RA, Pors K. Synthesis and biological evaluation of colchicine C-ring analogues tethered with aliphatic linkers suitable for prodrug derivatisation. Bioorg Med Chem Lett. 2012 Dec 15;22(24):7693-6. doi: 10.1016/j.bmcl.2012.09.104. Epub 2012 Oct 10
  • Sutherland M, Gill JH, Loadman PM, Laye JP, Sheldrake HM, Illingworth NA, Alandas MN, Cooper PA, Searcey M, Pors K, Shnyder SD, Patterson LH. Antitumor activity of a duocarmycin analogue rationalized to be metabolically activated by cytochrome P450 1A1 in human transitional cell carcinoma of the bladder. Mol Cancer Ther. 2013 Jan;12(1):27-37. doi: 10.1158/1535-7163.MCT-12-0405. Epub 2012 Oct 1
  • Abdallah QM, Phillips RM, Johansson F, Helleday T, Cosentino L, Abdel-Rahman H, Etzad J, Wheelhouse RT, Kiakos K, Bingham JP, Hartley JA, Patterson LH, Pors K. Minor structural modifications to alchemix influence mechanism of action and pharmacological activity. Biochem Pharmacol. 2012 Jun 1;83(11):1514-22. doi: 10.1016/j.bcp.2012.02.017. Epub 2012 Mar 1
  • Pors K, Loadman PM, Shnyder SD, Sutherland M, Sheldrake HM, Guino M, Kiakos K, Hartley JA, Searcey M, Patterson LH. Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity. Chem Commun (Camb). 2011 Nov 28;47(44):12062-4. doi: 10.1039/c1cc15638a. Epub 2011 Oct 14
  • Veiga JP, Cooper PA, Pors K, Patterson LH, Bibby MC, Shnyder SD. Use of the hollow fiber assay for the evaluation of DNA damaging agents. J Pharmacol Toxicol Methods. 2011 Nov-Dec;64(3):226-32. doi: 10.1016/j.vascn.2011.04.006. Epub 2011 Apr 30

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