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Dr Sarah Jones

Dr Sarah Jones

Reader in Pharmacology

  • Email address S.Jones4@wlv.ac.uk
  • Phone number 01902 322748
  • Faculty Faculty of Science and Engineering
  • Institute School of Pharmacy
  • Areas of expertise

    Bioportides (bioactive cell penetrating peptides) and Reproductive Health

    Identification and refinement of bioportides capable of penetrating human sperm cells to modulate the activities of intracellular proteins that control motility and fertilisation capacity

     

    Development of an Innovative Human Mast cell-based Therapeutic Platform

    The utilisation of inert CPPs to deliver bioactive cargoes into discrete compartments of human mast cells, and so enable their subsequent exocytosis by the physiological activation of regulated secretion

     

    Stabilised Bioportides for Therapeutic Development

    Evaluating the influence of chemical modifications on the biochemical and pharmacological properties of second-generation (proteolytically stable) bioportides, thus identifying candidates for therapeutic applications

     

    Peptide Antibiotics

    The design, synthesis and evaluation of potent antimicrobial mastoparan analogues with limited secretory and cytotoxic bioactivities towards human cells. Screening is carried out in collaboration with Community for Open Antimicrobial Drug Discovery, Institute for Molecular Biosciences, The University of Queensland and Welcome Trust

     

    Complex Tissue Models for the evaluation of CPP Technologies

    Evaluation of the planarian Schmidtea mediterranea as a model system for the discovery of cell penetrating peptides and bioportides. Consisting of 20% pluripotent stem cells and the ability to fully regenerate lost body parts, this organism providea a convenient model to further elucidate the role of CPP and bioportide technologies in stem cell biology, regenerative medicine and wound healing.

Dr Sarah Jones is a Reader in Pharmacology and a member of the Molecular Pharmacology Research Group. For the past 19 years, Sarah’s research has focussed on Cell Penetrating Peptides as a means to reach and modulate biological events within the cell. The ability of Cell Penetrating Peptides to target numerous and previously elusive intracellular candidate sites for therapeutic interventions could offer unparalleled opportunities for drug development and expand the repertoire of novel “druggable” targets.

With over 50 publications to date, numerous speaker invitations at International Symposia and co-editor of the book Bioactive Peptides, Sarah is now an established figure within the field of Cell Penetrating Peptides. Additionally, she has organized 3 International conferences including; a joint FEBS/Biochemical Society 4-day lecture course "Cell Penetrating Peptides" held at the Royal Society 2013, a Zing sponsored conference "Peptide Therapeutics 2012" and a Biochemical Society Focused Meeting "Cell Penetrating Peptides 2007.

On 25th July 2019, Sarah shall be hosting “Chemistry and Biology of Peptides 2019”, a free one day mini-symposium organised under the auspices of the Protein and Peptides Science Group of the Royal Society of Chemistry. The event will take place in the Chancellor’s Hall, University of Wolverhampton and will be followed by the “Early stage Researchers’ Meeting” on 26th July.

 

Cell Penetrating Peptide (CPP) technologies now provide a means of delivering previously impenetrable cargoes into the cell’s interior. As a member of the Molecular Pharmacology Group Sarah has played a major role in the development of bioactive CPPs, bioportides. This has resulted in a paradigm shift from the use of CPPs merely as inert vectors, to their applicability and therapeutic utility as modulators of intracellular protein-protein interactions. Identification of these novel cryptic CPPs within key signalling proteins has resulted in scientific publications regarding the utility of bioportide technology in apoptosis, angiogenesis and Parkinson’s disease pathophysiology, the latter of which comprised a pilot study funded by the Michael J Fox Foundation, “Evaluation of LRRK2-derived Bioportides as Functional Protein Modulators and Potential Therapeutics”.

CPPs, Bioportides and Sperm Motility. As an extension of this work, in 2013 the Molecular Pharmacology Group reported that CPPs readily enter spermatozoa. This development precipitated the subsequent identification of bioportides capable of penetrating human sperm cells to modulate the activities of intracellular proteins that control calcium signalling (Morris et al., 2015), motility and fertilisation capacity. Included in these studies was the pioneering work in the targeting of a spermatozoa-specific phosphatase, which controls sperm motility and fertilization capacity during epididymal transit. This technology offers potential for both the development of a non-hormonal male contraceptive and fertility treatments and has led to a collaborative patent with Professor Fardilha’s Team at the University of Aveiro, Portugal.

PPP1CC2 interactome-derived bioportide technologies for the control of sperm motility and male fertility. UK Patent Application (No. 1711620.3) filed 19th July 2017. 

This recent patent application describes bioportides that control male fertility has been submitted to the UK patent office by the University of Wolverhampton. Inventors include, Professor John Howl, Dr Sarah Jones, Professor Margarida Fardilha, Dr Joana Vieira da Silva and Ms. Maria João Freitas

Impact: The initial impact of these findings became fully apparent following the release of our paper in “Human Reproduction” 2013 and the subsequent optimism of those working within the fertility field. For many years those specialising in sperm physiology have been in search of a cell permeable agent which is compatible with sperm physiology. Hitherto, studies of intracellular biology have largely been restricted to de-membranated sperm models using powerful detergents which pose probable deleterious effects on protein function. Thus, the impact of these findings extends beyond the initial development of a male contraceptive, to include a valuable tool to probe and validate those protein targets which are integral to all aspects of sperm function.

Moreover, the impenetrable nature of sperm, combined with side effects associated with hormonal strategies are factors which have delayed the development of a male contraceptive. Targeting spermatozoa protein-protein interactions constitutes a more attractive therapeutic loci compared to current hormonal-dependent approaches which impose upon the hypothalamic-pituitary-gonadal axis and can lead to deleterious and sometime irreversible side effects. Our pioneering work has attracted headlines across the world, including coverage on BBC’s Horizon and Channel 4’s Live Well for Longer. This most fruitful and collaborative venture is currently focussed upon driving forward a male contraceptive into early drug development.

Additional International Collaborations. Strong international collaborative ventures lie at the heart of the molecular pharmacology group and have led to the development of a novel glioma-homing peptidyl drug delivery system and European Patent. entitled “chimeric constructs between glioma-homing peptide and cell-penetrating peptide, gHoPe2”, this joint patent is with CePeP III AB, Stockholm, Sweden and the University of Tartu, Estonia. European Patent filed 7th June 2012. Reference 12171160.0-1216.

Membership of professional bodies

Elected Fellow of the Royal Society of Biology, 1st January 2017

Peer-elected member of the Scientific Committee of the European Peptide Society (2016-2020).

Peer-elected member of the Protein and Peptide Science Group of the Royal Society of Chemistry (2015-2019)

 

2005 Doctor of Philosophy Design Synthesis and Evaluation of Receptor Mimetic Peptides as Signal Transduction Modulators, University of Wolverhampton, Molecular Pharmacology Research Group

 

2000 BSc (Hons) Biomedical Sciences, First Class, University of Wolverhampton

Institute of Biomedical Science, the Presidents Prize, 2000

The Physiological Society, Undergraduate Prize for Physiology, 2000

Patients’ Aid Association Prizes, 1997 and 1998, for outstanding performance in the field of undergraduate Biomedical Science

 

1995 Diploma in Psychiatric Nursing/Registered Mental Nurse, University of Birmingham and the Queen Elizabeth College of Nursing, Birmingham

 

2015 Fellow of the Higher Education Academy

 

2015 Post Graduate Certificate Academic Practice (PGCE)

Selected Publications

Bashir, A.I.J., Kankipati, C.S., Jones, S., Newman, R.M., Safrany, S.T., Perry, C.J., Nicholl, I.D. (2019) A novel mechanism for the anticancer activity of aspirin and salicylates. Int. J. Oncol. 54, 1256-1270.

Jones, S., Osman, S. & Howl, J. (2019) The planarian Schmidtea mediterranea as a model system for the discovery and characterization of cell penetrating peptides and bioportides. Chemical Biology and Drug Design. Feb 20. doi: 10.1111/cbdd.13483. [Epub ahead of print]

Jones, S., Osman, S. & Howl, J. (2018) A high-throughput synthetic platform enables the discovery of proteomimetic cell penetrating peptides and bioportides. International Journal of Peptide Research and Therapeutics - Jones, Sarah; Osman, Shaimaa; Howl, John. Int. J. Pept. Res. Ther.https://doi.org/10.1007/s10989-018-9681-1

Richardson, A., Muir, L., Mousdell, S., Sexton, D., Jones, S., Howl, J. & Ross, K. (2018) Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan. BMC Research Notes 11:82,https://doi.org/10.1186/s13104-018-3192-1, open access.

Howl, J., Howl, L.J. & Jones, S. (2018) The cationic tetradecapeptide mastoparan as a privileged structure for drug discovery: Enhanced antimicrobial properties of mitoparan analogues modified at position-14. Peptides 101, 95-105.

Jones. S., Uusna, J., Langel, Ü. & Howl, J. (2016) Intracellular Target-Specific Accretion of Cell Penetrating Peptides and Bioportides: Ultrastructural and Biological Correlates. Bioconjug. Chem. 27(1), 121-129

Morris, J., Jones, S., Howl, J., Lukanowska, M., Lefievre, L. & Publicover, S. (2015) Cell penetrating peptides, targeting the regulation of store-operated 1 channels, slow decay of the progesterone-induced [Ca2+ ]i signal in human sperm. Molecular Human Reproduction 21, 563-570.

Howl, J. & Jones, S. (2015) Cell penetrating peptide-mediated transport enables the regulated secretion of accumulated cargoes from mast cells. J. Control. Release 202, 108-117.

Howl, J. & Jones, S. (2015) Insights into the molecular mechanisms of action of bioportides: a strategy to target protein-protein interaction. Expert Reviews in Molecular Medicine 17, e1 doi:10.1017/erm.2014.24.

Howl, J. & Jones, S. (2015) Protein Mimicry and the Design of Bioactive Cell Penetrating Peptides. Methods in Molecular Biology, 1324, 177-190

Lukanowska, M., Howl, J. & Jones, S. (2013) Bioportides: bioactive cell-penetrating peptides that modulate cellular dynamics. Biotechnology Journal 8, 918-930.

Mehta, A., Shervington, A., Howl, J., Jones, S., Shervington, L. (2013) Can RNAi-mediated hsp90 αknockdown in combination with 17-AAG be a therapy for glioma? FEBS Open Bio 3, 271-278. http://dx.doi.org/10.1016/j.fob.2013.06.002.

Jones, S., Lukanowska, M., Suhorutsenko,J., Oxenham, S., Barratt, C., Publicover, S., Copolovici, D.M., Langel,Ü. and Howl, J. (2013) Intracellular translocation and differential accumulation of cell penetrating peptides into bovine spermatozoa: evaluation of efficient delivery vectors that do not compromise human sperm motility. Human Reproduction 28, 1874-1889

Eriste, E., Kurrikoff, K., Suhorutšenko, J., Oskolkov, N., Copolovici, Dana, Jones, S., Howl, J., Laakkonen, P. and Langel, U. (2012) Peptide-based glioma-targeted drug delivery vector gHoPe2. Biocongugate Chemistry 24, 305-313

Howl, J.,Matou-Nasri, S., West, D.S., Farquhar, M., Slaninová, J., Östenson, G.C., Zorko, M., Östlund, P., Kumar, S., Langel, Ü., McKeating, J. and Jones. S. (2012)Bioportide: An Emergent Concept of Bioactive Cell Penetrating Peptides. Cellular and Molecular Life Sciences 69, 2951-2966.

Jones, S. &Howl, J.(2012) Enantiomer-specific bioactivities of peptidomimetic analogues of mastoparan and mitoparan: characterization of inverso mastoparan as a highly efficient cell penetrating peptide. Biocongugate Chem. 23, 47-56

Jones, S., Holm, T., Mager, I., Langel, U. and Howl, J. (2010)Characterisation of Bioactive Cell Penetrating Peptides from Human Cytochrome c: Protein Mimicry and the Development of a Novel Apoptogenic Agent. Chemistry and Biology 17, 735-744

Jones, S. & Howl, J. (2010) Applications of cell penetrating peptides as signal transduction modulators for the selective induction of apoptosis. In: Cell Penetrating Peptides: Methods and Protocols, Methods in Molecular Biology, (Langel, U. ed). Humana Press, New York, USA.

Howl, J. & Jones, S. (2009) Transport molecules using reverse sequence HIV-Tat polypeptides: not just any old Tat? (WO200808225). Expert Opin. Ther. Pat. 19, 1329-1333.

Howl, J & Jones, S. (2009) Bioactive Peptides. Taylor & Francis/CRC Press. ISBN 9781420061147.

Jones, S. & Howl, J. (2009) Mastoparans. In: Bioactive Peptides (Howl, J. & Jones, S. eds). Taylor & Francis/CRC Press. ISBN 9781420061147

Jones, S., Martel, C., Belzacq-Casagrande, A.S., Brenner, C. & Howl, J. (2008) Mitoparan and target-selective chimeric analogues: membrane translocation and intracellular redistribution induces mitochondrial apoptosis. Biochim. Biophys. Acta. Molecular Cell Research. 1783, 849-863

Farquhar, M.J., Harris, H.J., Jones, S., Nielsen, S.U., Brimacombe, C.L., Molina, S., Toms, G.L., Maurel, P., Howl, J., van Ijzendoorn, S.V.D., Balfe, P., & McKeating, J.A. (2008) Protein Kinase A dependent step(s) in Hepatitis C virus entry and infectivity. Journal of Virology. 82, 8797-8811.

Howl, J. & Jones, S. (2008)Proteomimetic Cell Penetrating Peptides. Int. J. Pept. Res. Ther. 14, 359-366.

Howl, J., Nicholl, I.D. & Jones, S. (2007) The many futures for cell penetrating peptides: how soon is now? Biochem. Soc. Trans. 35, 767-769.

Jones, S. & Howl, J. (2006) Applications of cell-penetrating peptides as signal transduction modulators. In: Handbook of Cell Penetrating Peptides, 2nd edition (Langel, U. ed) CRC Press, Washington, D.C. USA.

Jones, S. & Howl, J. (2006) Biological applications of the receptor mimetic peptide mastoparan. Current Protein and Peptide Science 7, 501-508

Jones, S., Farquhar, M., Martin, A. & Howl, J. (2005) Intracellular translocation of the decapeptide carboxyl terminal of Gi3α induces the dual phosphorylation of p42/p44 MAP kinases. Biochim. Biophys. Acta. Molecular Cell Research 1745, 207-214.

Foreman, M.A, Gu, Y., Howl, J.D., Jones, S. & Publicover, S.J. (2005) Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells. J. Cell. Physiol. 204, 704-713.

Jones, S. & Howl, J. (2004) Charge delocalisation and the design of novel mastoparan (MP) analogues: Enhanced cytotoxicity and secretory efficacy of [Lys5,Lys8,Aib10]MP. Regul. Pept. 121, 121-128.

Jones, S. & Howl,J. (2004) Amphiphilic peptide engineering: Charge delocalisation and the design of novel mastoparan analogues. In: Peptides 2004 (Flegel, M., Fridkin, M., Gilon, C. & Slaninova, J. eds) Kenes International, Tel Aviv.

Howl, J., Jones, S. & Farquhar, M. (2003) Intracellular delivery of bioactive peptides to RBL-2H3 cells induces ß-hexoseaminidase secretion and phospholipase D activation. ChemBioChem 4, 1312-1316.

Jones, S. & Howl, J. (2003) Cannnabinoid receptor systems: Therapeutic targets for tumour intervention. Expert Opin. Ther. Targets 7, 749-758.

Brown, J., Reading, S.J., Jones, S., Fitchett, C.J., Howl, J., Martin, A., Longland, C.L., Michelangeli, F., Dubrova, Y.E., & Brown, C.A. (2000) Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83. Lab. Invest. 80, 37-45.

Additional International Collaborations

Strong international collaborative ventures lie at the heart of the molecular pharmacology group and have led to the development of a novel glioma-homing peptidyl drug delivery system and European Patent. entitled “chimeric constructs between glioma-homing peptide and cell-penetrating peptide, gHoPe2”, this joint patent is with CePeP III AB, Stockholm, Sweden and the University of Tartu, Estonia. European Patent filed 7th June 2012. Reference 12171160.0-1216.

 

Speaker Invitations

2018   Central Cellular Pathology Society Conference - CELLibration 26th -28th October. “Penetrating the Impenetrable: Progress towards a Non-hormonal Male Contraceptive.” Invited Speaker.

2018   35th European Peptide Symposium, 26th – 31st August, Dublin City University, Ireland. “Penetrating the Impenetrable: Progress towards a Non-hormonal Male Contraceptive.” Invited Speaker.

2018 FinMedChem– Medicinal Chemistry Meets Pharmacology Symposium, Helsinki, Finland, 24th-25th April. “Penetrating the Impenetrable: Progress towards a Non-hormonal Male Contraceptive.” Plenary Lecture

2017 Liverpool University, Mersey Region Group for Sexual Health Training, 6th April. “A Step Forward in the Development of the Male Contraceptive; Penetrating the Impenetrable.” Invited Speaker

2015 Marcus Evans Discovery Summit, Munich, 4th-6th November. “Uniting Clinical and Academic Research Aims to Advance Future Developments in Peptide Therapeutics”, joint presentation with Professor John Howl. Distinguished Speaker

2015 Kings College Lecture Series, London, 14th October. “Bioportides: Bioactive Cell Penetrating Peptides, From Somatic to Sperm.” Guest Speaker

2015 Cell Penetrating Peptides in Paris, University Pierre and Marie Curie, Sorbonne Universites, CNRS-ENS-UPMC, 1st-3rd July. “Bioportides: Bioactive Cell Penetrating Peptides, From Somatic to Sperm.” Keynote Speaker

2014 Royal Society of Chemistry’s Emerging Technologies Competition, June. Finalists, bioportide technology (Pantechnia Ltd- John Howl & Sarah Jones).

2013 Marcus Evans Evolution Summit,Monte Carlo Monaco, Distinguished Speaker

2013 Cell Penetrating Peptides, The Royal Society London, UK, Conference Chair and Speaker

2013 Marcus Evans Discovery Summit,Monte Carlo Monaco, Distinguished Speaker

2012 MedImmune (AstraZeneca), Cambridge UK, Seminar entitled “Bioportides”, Invited Speaker

2012 32nd European Peptide Symposium, Megaron Athens, Greece, Invited Speaker.

2012 The Michael J. Fox Foundation for Parkinson’s Research, The Edmond J. Safra Philanthropic Foundation Conference Room, New York.  LRRK2 Assessment, Invited Speaker.

2012 Peptide Therapeutics, Lanzarote, Spain, Conference Chair and Speaker

2010 31st European Peptide Satellite Symposium on Cell Penetrating Peptides, Panum Institute, University of Copenhagen, Copenhagen, Denmark, Invited Speaker

2009 Chemistry and Biology of Peptides, Oxford University, UK, Invited Speaker

2008 30th European Peptide Symposium, Cell Penetrating Peptide Meeting, Biomedicum Helsinki, Finland, Invited Speaker

2007 4th International Peptide Symposium in conjunction with 7th Australian Peptide Conference and 2nd Asia-Pacific International Peptide Symposium, Cairns, Australia, Invited Speaker

2007 British Council of Slovenia, Café Scientifique, Llubjana, Slovenia, Invited Speaker

2006 29th European Peptide Symposium, Gdansk, Poland, Invited Speaker