Dr Sarah Brown
Demonstrator
- Email address Sarah.Brown@wlv.ac.uk
- Phone number 01902 321130
- Faculty Faculty of Science and Engineering
- Institute School of Pharmacy
- Areas of expertise
Cell and molecular biology: Extensive cell culture • cytotoxicity assays • flow cytometry techniques (apoptosis, cell cycle, ROS, protein expression) • western blotting • EMSA • separation/isolation of cell populations • immuno-fluorescence techniques • confocal imaging • live cell imaging • transfections • dual reporter gene luciferase assays • clonogenic studies
After completing my undergraduate degree in Biochemistry at the University of Salford I did a PhD at the University of Manchester where I worked in the Leukaemia Research Fund laboratory and investigated the phenotypic, morphological, and functional comparison between normal and leukaemia derived dendritic cells.
I joined the University of Wolverhampton in 2005 as a Research Fellow investigating the potential of using the anti-alcoholism drug disulfiram in combination with copper as a novel chemosensitiser for breast cancer and brain tumour chemotherapy.
In 2012 I was appointed as a Demonstrator in the School of Pharmacy
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.
Brown S., Hutchinson CV., Aspinall-O'Dea M., Whetton AD., Johnson SM., Unwin KR., Burthem J. (2014) Monocyte-derived dendritic cells from chronic myeloid leukaemia have abnormal maturation and cytoskeletal function that is associated with defective localisation and signalling by normal ABL1 protein. European Journal of Haematology 2014 Mar 11. doi: 10.1111/ejh.12306. [Epub ahead of print]
Kannappan, V., Brown, S., Liu, P., Tawari, PE., Armesilla, AL., Darling, JL., Wang, W. (2014) Aldehyde dehydrogenase activity induces chemoresistance in glioblastoma cell lines. In preparation to submit to British Journal of Cancer
Liu, P., Brown, S., Kannappan, V., Tawari, PE., Jiang, W., Armesilla, AL., Darling, JL., Wang, W. (2014) Tackling hypoxia-induced NFκB activation to target breast cancer stem cells In preparation to submit to Carcinogenesis
Liu, P., Kumar, IS., Brown, S., Kannappan, V., Tawari, PE., Tang, JZ., Jiang, W., Armesilla, AL., Darling, JL., Wang, W. (2013) Disulfiram targets cancer stem like cells and reverses resistance and cross-resistance in acquired paclitaxel –resistant triple-negative breast cancer cells. British Journal of Cancer 2013 Oct 1: 109, 1876-1885
Liu, P., Brown, S., Channathodiyil, P., Kannappan, V., Armesilla, AL., Darling, JL., Wang, W. (2013) Reply to the letter to the Editor: Comment on ‘Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells’. British Journal of Cancer 2013 Mar 5; 108, 994 (joint first author)
Liu, P., Brown, S., Goktug, T., Channathodiyil, P., Kannappan, V., Hugnot, JP., Guichet, PO., Bian, X., Armesilla, AL., Darling, JL., Wang, W. (2012) Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells. British Journal of Cancer 2012 Oct 23;107(9):1488-97 (joint 1st author)
Baggott, R., Mohamed, TMA., Oceandy, D., Holton, ML., Blanc, MC., Roux-Soro, SC., Brown, S., Brown, JE., Cartwright, EJ., Wang, W., Neyses, L., Armesilla, AL. (2012) Disruption of the interaction between PMCA2 and calcineurin triggers apoptosis and enhances paclitaxel-induced cytotoxicity in breast cancer cells. Carcinogenesis 33 (12): 2362-2368
Özkan, M., Mutiso, PBC., Nahar, L., Liu, P., Brown, S., Wang, W., Sarker, SD. (2012). Zanthoxylum usambarense (Eng.) Kokwaro (Rutaceae) extracts inhibit the growth of the breast cancer cell lines MDA-MB-231 and MCF-7, but not the brain tumour cell line U251 in vitro. Phytotherapy Research 2013 May;27(5):787-90
Yip, NC., Fombon, IS., Liu, P., Brown, S., Kannappan, V., Armesilla, AL., Xu, B., Cassidy, J., Darling, J., Wang, W. (2011) Disulfiram modulated ROS–MAPK and NFκB pathways and targeted breast cancer cells with cancer stem cell-like properties. British Journal of Cancer 104; 1564–1574