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researcher

Helen Sheldrake

Lecturer - Organic & Medicinal Chemistry

Faculty/Dept/School School of Pharmacy and Medical Sciences
(Faculty of Life Sciences)
Emailh.sheldrake@bradford.ac.uk
Telephone +441274 236858

Biography

Helen Sheldrake studied Natural Sciences followed by a PhD in natural product synthesis at the University of Cambridge. After postdoctoral work at The University of Manchester, she joined the Institute of Cancer Therapeutics, University of Bradford as a RCUK Academic Fellow in Medicinal Chemistry. She is now a Lecturer in the School of Pharmacy and Medical Sciences, and School Health and Safety Lead.

Research

New synthetic methods for biologically active/druglike molecules. Design and synthesis of integrin antagonists. Total synthesis.

The integrins are a family of transmembrane receptors which mediate cell-cell and cell-ECM adhesion, and signalling across the cell membrane involved in pathways controlling cell migration, proliferation, differentiation, cell survival and apoptosis. In cancers, their vital role in the cross-talk between the cell and extracellular matrix enhances the growth, migration, invasion and metastasis of cancer cells. The RGD-binding subfamily of integrins are of particular interest as anticancer targets, since there is strong evidence that their expression in cancers is correlated with tumour progression, treatment resistance, and a cancer stem cell phenotype. Research areas currently under investigation include:
- Synthesis and characterisation of new integrin targeting small molecules for the treatment of advanced cancers, particularly metastatic prostate cancer and malignant melanoma.
- Development of personalised anti-integrin agents: Identification of the optimum combination of integrins to target for effective treatment of a particular tumour.
- Investigation of combination therapies to combat integrin-mediated resistance to existing anticancer agents.

Outside the integrin area, I am interested in the synthesis of biologically active natural products, and derivatives.
If you are interested in applying for a PhD or postdoc in one of these areas, please contact me directly.
Date Role Title / Description Funder Award
- PINew strategies for improving efficacy of integrin antagonism
- PITotal synthesis of Nigramide Q
Research collaborators
NameMartin Brinkworth
TypeI
DescriptionNew applications of integrin modulating small molecules
 
NameKrzysztof Paluch
TypeI
DescriptionSynthesis and characterisation of novel antibiotic prodrugs
 
Contract Researchers
NameAndrew Gordon
RoleResearch Assistant
ProjectDevelopment of dual beta3 integrin antagonists as a novel anti-metastatic therapeutic for castration-resistant prostate cancer
Duration2011-2012
 
NameAdam Throup
RoleResearch Assistant
ProjectDesign, Synthesis and Applications of Chiral Cyclobutanes
Duration2009-2011
 

Professional activities

  • 01-JAN-07: University of Bradford - RCUK Academic Fellow in Medicinal Chemistry
  • 01-JAN-04: The University of Manchester - Postdoctoral Research Associate
  • 01-JAN-15: - Fellow of the Higher Education Academy
  • 01-JAN-04: University of Cambridge - PhD
  • 01-JAN-01: University of Cambridge - MSci

Publications

Peer Reviewed Journal
TitleExploration of [2 + 2 + 2] cyclotrimerisation methodology to prepare tetrahydroisoquinoline-based compounds with potential aldo-keto reductase 1C3 target affinity (2019)
AuthorsSantos A.;Sheldrake H.;Ibrahim A.;Danta C.;Bonanni D.;Daga M.;Oliaro-Bosso S.;Boschi D.;Lolli M.;Pors K.
JournalMedChemComm
DOI10.1039/c9md00201d
 
TitleRGD-Binding Integrins in Head and Neck Cancers (2017)
AuthorsAhmedah, H.T.; Patterson, Laurence H.; Shnyder, Steven D.; Sheldrake, Helen M.
 
TitleIntramolecular thermal stepwise [2 + 2] cycloadditions: investigation of a stereoselective synthesis of [n.2.0]-bicyclolactones (2016)
AuthorsThroup, Adam; Patterson, Laurence H.; Sheldrake, Helen M.
 
TitleSolid-phase synthesis of duocarmycin analogues and the effect of C-terminal substitution on biological activity (2015)
AuthorsStephenson, M.J.; Howell, L.A.; O'Connell, M.A.; Fox, K.R.; Adcock, C.; Kingston, J.; Sheldrake, Helen M.; Pors, Klaus; Collingwood, S.P.; Searcey, M.
 
TitleStrategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists (2014)
AuthorsSheldrake, Helen M.; Patterson, Laurence H.
 
TitleColon cancer-specific cytochrome P450 2W1 converts duocarmycin analogues into potent tumor cytotoxins (2013)
AuthorsTravica, S.; Pors, Klaus; Loadman, Paul M.; Shnyder, Steven D.; Johansson, I.; Alandas, Mohammed N.; Sheldrake, Helen M.; Mkrtchian, S.; Patterson, Laurence H.; Ingelman-Sundberg, M.
 
TitleRe-engineering of the Duocarmycin Structural Architecture Enables Bioprecursor Development Targeting CYP1A1 and CYP2W1 for Biological Activity (2013)
AuthorsSheldrake, Helen M.; Travica, S.; Johansson, I.; Loadman, Paul M.; Sutherland, Mark H.; Elsalem, Lina M.I.; Illingworth, Nicola A.; Cresswell, Alexander J.; Reuillon, Tristan; Shnyder, Steven D.; Mkrtchian, S.; Searcey, M.; Ingelman-Sundberg, M.; Patterson, Laurence H.; Pors, Klaus
 
TitleAntitumor activity of a duocarmycin analogue rationalized to be metabolically activated by cytochrome P450 1A1 in human transitional cell carcinoma of the bladder (2013)
AuthorsSutherland, Mark H.; Gill, Jason H.; Loadman, Paul M.; Laye, Jonathan P.; Sheldrake, Helen M.; Illingworth, Nicola A.; Alandas, Mohammed N.; Cooper, Patricia A.; Searcey, M.; Pors, Klaus; Shnyder, Steven D.; Patterson, Laurence H.
 
TitleModification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity (2011)
AuthorsPors, Klaus; Loadman, Paul M.; Shnyder, Steven D.; Sutherland, Mark H.; Sheldrake, Helen M.; Guino, M.; Kiakos, K.; Hartley, J.A.; Searcey, M.; Patterson, Laurence H.
 
TitleSynthesis of the originally proposed structure of elatenyne and an enyne from Laurencia majuscula (2009)
AuthorsSheldrake, Helen M.; Jamieson, C.; Pascu, S.I.; Burton, J.W.
 
TitleChemical and Biological Explorations of the Family of CC-1065 and the Duocarmycin Natural Products. (2009)
AuthorsGhosh, Nandita; Sheldrake, Helen M.; Searcey, M.; Pors, Klaus
 
TitleFunction and Antagonism of beta3 integrins in the development of cancer therapy (2009)
AuthorsSheldrake, Helen M.; Patterson, Laurence H.
 
TitleRapid stereoselective access to the tetracyclic core of puupehenone and related sponge metabolites using metal-free radical cyclisations of cyclohexenyl-substituted 3-bromochroman-4-ones. (2008)
AuthorsPritchard, R.P.; Sheldrake, Helen M.; Taylor, I.Z.; Wallace, T.W.
 
TitleReduction of Propargylic Sulfones to (Z)-Allylic Sulfones using Zinc and Ammonium Chloride. (2007)
AuthorsSheldrake, Helen M.; Wallace, T.W.
 
Other Publication
Other typeReviews
TitleRGD-binding integrins in head and neck cancers (2017)
AuthorsAhmedah H.;Patterson L.;Shnyder S.;Sheldrake H.
JournalCancers
DOI10.3390/cancers9060056
 
Other typeReviews
TitleStrategies to inhibit tumor associated integrin receptors: Rationale for dual and multi-antagonists (2014)
AuthorsSheldrake H.;Patterson L.
JournalJournal of Medicinal Chemistry
DOI10.1021/jm5000547
 
Other typeReviews
TitleRGD-binding integrins in prostate cancer: Expression patterns and therapeutic prospects against bone metastasis (2012)
AuthorsSutherland M.;Gordon A.;Shnyder S.;Patterson L.;Sheldrake H.
JournalCancers
DOI10.3390/cancers4041106
 
Other typeReviews
TitleChemical and biological explorations of the family of CC-1065 and the duocarmycin natural products (2009)
AuthorsGhosh N.;Sheldrake H.;Searcey M.;Pors K.
JournalCurrent Topics in Medicinal Chemistry
DOI10.2174/156802609789909812
 
Other typeReviews
TitleFunction and antagonism of β3 integrins in the development of cancer therapy (2009)
AuthorsSheldrake H.;Patterson L.
JournalCurrent Cancer Drug Targets
DOI10.2174/156800909788486713