Dr Helen Sheldrake
Assistant Professor
| Faculty/Dept/School |
School of Pharmacy and Medical Sciences (Faculty of Life Sciences) |
|---|---|
| h.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 |
|---|---|---|---|---|
| - | PI | New strategies for improving efficacy of integrin antagonism | ||
| - | PI | Total synthesis of Nigramide Q |
| Research collaborators | |
|---|---|
| Name | Martin Brinkworth |
| Type | I |
| Description | New applications of integrin modulating small molecules |
| Name | Krzysztof Paluch |
| Type | I |
| Description | Synthesis and characterisation of novel antibiotic prodrugs |
| Contract Researchers | |
|---|---|
| Name | Adam Throup |
| Role | Research Assistant |
| Project | Design, Synthesis and Applications of Chiral Cyclobutanes |
| Duration | 2009-2011 |
| Name | Andrew Gordon |
| Role | Research Assistant |
| Project | Development of dual beta3 integrin antagonists as a novel anti-metastatic therapeutic for castration-resistant prostate cancer |
| Duration | 2011-2012 |
Teaching
Teaching interests
Current teaching activities:
Phase Leader: head of Clinical Sciences BSc Years 1 + 2
Module Leader: CLS3004-B Chemistry for Clinical Sciences, CLS5013-B Pharmacology and Therapeutics, CLS6001-B Clinical Pharmacology, LIS7022-B Critical Appraisal
Lecturer: Principles of Drug Discovery; Case Studies in Drug Discovery; Preclinical Models for Drug Evaluation; Practical Skills in Research; Research projects; Personal tutor Clinical Sciences years 1-3
Previous teaching highlights:
Programme leader: MSc Cancer Pharmacology 2015-2019
Lecturer: Biological Organic Chemistry
Practical class leader: Chemistry for Engineers
Professional activities
- 01-JAN-15: Fellow of the Higher Education Academy
- 01-JAN-04: University of Cambridge - PhD
- 01-JAN-01: University of Cambridge - MSci
- 01-JAN-07: University of Bradford - RCUK Academic Fellow in Medicinal Chemistry
- 01-JAN-04: The University of Manchester - Postdoctoral Research Associate
Publications
| Title | Synthesis and Biological Evaluation of Cyclobutane-Based β3 Integrin Antagonists: A Novel Approach to Targeting Integrins for Cancer Therapy (2023) |
|---|---|
| Authors | Mark Sutherland, Andrew Gordon, Fatemah OFO Al-Shammari, Adam Throup, Amy Cilia La Corte, Helen Philippou, Steven D Shnyder, Laurence H Patterson, Helen M Sheldrake |
| Journal | Cancers |
| DOI | https://doi.org/10.3390/cancers15164023 |
| Title | Probing cytochrome P450 (CYP) bioactivation with chloromethylindoline bioprecursors derived from the duocarmycin family of compounds. (2021) |
| Authors | Ortuzar N;Karu K;Presa D;Morais GR;Sheldrake HM;Shnyder SD;Barnieh FM;Loadman PM;Patterson LH;Pors K;Searcey M; |
| Journal | Bioorganic and Medicinal Chemistry |
| DOI | 10.1016/j.bmc.2021.116167 |
| Title | Exploration of [2 + 2 + 2] cyclotrimerisation methodology to prepare tetrahydroisoquinoline-based compounds with potential aldo-keto reductase 1C3 target affinity (2019) |
| Authors | Santos A.;Sheldrake H.;Ibrahim A.;Danta C.;Bonanni D.;Daga M.;Oliaro-Bosso S.;Boschi D.;Lolli M.;Pors K. |
| Journal | MedChemComm |
| DOI | 10.1039/c9md00201d |
| Title | RGD-Binding Integrins in Head and Neck Cancers (2017) |
| Authors | Ahmedah, H.T.; Patterson, Laurence H.; Shnyder, Steven D.; Sheldrake, Helen M. |
| Title | Intramolecular thermal stepwise [2 + 2] cycloadditions: investigation of a stereoselective synthesis of [n.2.0]-bicyclolactones (2016) |
| Authors | Throup, Adam; Patterson, Laurence H.; Sheldrake, Helen M. |
| Title | Solid-phase synthesis of duocarmycin analogues and the effect of C-terminal substitution on biological activity (2015) |
| Authors | Stephenson, 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. |
| Title | Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists (2014) |
| Authors | Sheldrake, Helen M.; Patterson, Laurence H. |
| Title | Antitumor activity of a duocarmycin analogue rationalized to be metabolically activated by cytochrome P450 1A1 in human transitional cell carcinoma of the bladder (2013) |
| Authors | Sutherland, 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. |
| Title | Colon cancer-specific cytochrome P450 2W1 converts duocarmycin analogues into potent tumor cytotoxins (2013) |
| Authors | Travica, 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. |
| Title | Re-engineering of the Duocarmycin Structural Architecture Enables Bioprecursor Development Targeting CYP1A1 and CYP2W1 for Biological Activity (2013) |
| Authors | Sheldrake, 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 |
| Title | Modification of the duocarmycin pharmacophore enables CYP1A1 targeting for biological activity (2011) |
| Authors | Pors, 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. |
| Title | Chemical and Biological Explorations of the Family of CC-1065 and the Duocarmycin Natural Products. (2009) |
| Authors | Ghosh, Nandita; Sheldrake, Helen M.; Searcey, M.; Pors, Klaus |
| Title | Function and Antagonism of beta3 integrins in the development of cancer therapy (2009) |
| Authors | Sheldrake, Helen M.; Patterson, Laurence H. |
| Title | Synthesis of the originally proposed structure of elatenyne and an enyne from Laurencia majuscula (2009) |
| Authors | Sheldrake, Helen M.; Jamieson, C.; Pascu, S.I.; Burton, J.W. |
| Title | Rapid 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) |
| Authors | Pritchard, R.P.; Sheldrake, Helen M.; Taylor, I.Z.; Wallace, T.W. |
| Title | Reduction of Propargylic Sulfones to (Z)-Allylic Sulfones using Zinc and Ammonium Chloride. (2007) |
| Authors | Sheldrake, Helen M.; Wallace, T.W. |
| Other type | Reviews |
|---|---|
| Title | RGD-binding integrins in head and neck cancers (2017) |
| Authors | Ahmedah H.;Patterson L.;Shnyder S.;Sheldrake H. |
| Journal | Cancers |
| DOI | 10.3390/cancers9060056 |
| Other type | Reviews |
| Title | Strategies to inhibit tumor associated integrin receptors: Rationale for dual and multi-antagonists (2014) |
| Authors | Sheldrake H.;Patterson L. |
| Journal | Journal of Medicinal Chemistry |
| DOI | 10.1021/jm5000547 |
| Other type | Reviews |
| Title | RGD-binding integrins in prostate cancer: Expression patterns and therapeutic prospects against bone metastasis (2012) |
| Authors | Sutherland M.;Gordon A.;Shnyder S.;Patterson L.;Sheldrake H. |
| Journal | Cancers |
| DOI | 10.3390/cancers4041106 |
| Other type | Reviews |
| Title | Chemical and biological explorations of the family of CC-1065 and the duocarmycin natural products (2009) |
| Authors | Ghosh N.;Sheldrake H.;Searcey M.;Pors K. |
| Journal | Current Topics in Medicinal Chemistry |
| DOI | 10.2174/156802609789909812 |
| Other type | Reviews |
| Title | Function and antagonism of β |
| Authors | Sheldrake H.;Patterson L. |
| Journal | Current Cancer Drug Targets |
| DOI | 10.2174/156800909788486713 |