Gillian Farnie

Principal Investigator

University of Oxford

Gillian Farnie studied pharmacology at the University of Liverpool (UK) and did her PhD in molecular oncology at the Northern Institute for Cancer Research at the University of Newcastle upon Tyne, UK (2002).  She then had 6 years postdoctoral training in breast biology and breast cancer, developing novel 3D culture systems to grow human ductal carcinoma in situ (DCIS) and investigating epidermal growth factor and Notch signalling.  During collaborations with Dr Rob Clarke she became interested in cancer stem cell (CSC) signalling and was awarded an esteemed 5-year Breast Cancer Now Scientific Fellowship (2008) to start her research group. 

Based at the Manchester Cancer Research Centre her research focused on the role of breast CSCs in the resistance to radio and chemotherapy, exploring FAK and Wnt signalling as well as metabolic and epigenetic targets.  Aligned with these studies her lab is also developing bespoke hydrogel models of breast progression in collaboration with Dr Cathy Merry and Prof Tony Howell.

Research Areas

The Cell Biology group will innovate and develop assays to validate in-cell efficacy of established and new probe families which include bromodomains, Nudix hydrolases, deaminase and DENN domains.  Each assay will be developed to address the unique biology of the target using molecular biology (inc CRISPR, RNAseq, ChIP, Mass Spectrocopy) and confocal microscopy (HTS/HCS). Further detailed investigations into the biological mechanism and disease target will be carried out both in-house and with academic and pharmaceutical industry collaborations.  By advancing SGC probes into cellular assays we aim to produce pre-clinical in vitro data to enable the translation of SGC probes into a disease area within the clinic. 

Gillian’s research interests include disease heterogeneity, multicellular and 3D disease models. 

Publications

Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis.
Eyre, R; Alférez, DG; Spence, K; Kamal, M; Shaw, FL; Simões, BM; Santiago-Gómez, A; Sarmiento-Castro, A; Bramley, M; Absar, M; Saad, Z; Chatterjee, S; Kirwan, C; Gandhi, A; Armstrong, AC; Wardley, AM; O'Brien, CS; Farnie, G; Howell, SJ; Clarke, RB;
Journal of Mammary Gland Biology and Neoplasia. 2016 21:99-109. doi: 10.1007/s10911-016-9361-8
PMID: 27680982

Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity.
Simões, BM; O'Brien, CS; Eyre, R; Silva, A; Yu, L; Sarmiento-Castro, A; Alférez, DG; Spence, K; Santiago-Gómez, A; Chemi, F; Acar, A; Gandhi, A; Howell, A; Brennan, K; Rydén, L; Catalano, S; Andó, S; Gee, J; Ucar, A; Sims, AH; Marangoni, E; Farnie, G; Landberg, G; Howell, SJ; Clarke, RB;
Cell Reports. 2015 12:1968-1977. doi: 10.1016/j.celrep.2015.08.050
PMID: 26387946

Focal adhesion kinase and Wnt signaling regulate human ductal carcinoma in situ stem cell activity and response to radiotherapy.
Williams, KE; Bundred, NJ; Landberg, G; Clarke, RB; Farnie, G;
STEM CELLS. 2015 33:327-341. doi: 10.1002/stem.1843
PMID: 25187396

Targeting CXCR1/2 significantly reduces breast cancer stem cell activity and increases the efficacy of inhibiting HER2 via HER2-dependent and -independent mechanisms.
Singh, JK; Farnie, G; Bundred, NJ; Simões, BM; Shergill, A; Landberg, G; Howell, SJ; Clarke, RB;
Clinical Cancer Research. 2013 19:643-656. doi: 10.1158/1078-0432.CCR-12-1063
PMID: 23149820

Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor.
Harrison, H; Farnie, G; Howell, SJ; Rock, RE; Stylianou, S; Brennan, KR; Bundred, NJ; Clarke, RB;
Cancer Research. 2010 70:709-718. doi: 10.1158/0008-5472.CAN-09-1681
PMID: 20068161

Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways.
Farnie, G; Clarke, RB; Spence, K; Pinnock, N; Brennan, K; Anderson, NG; Bundred, NJ;
JNCI: Journal of the National Cancer Institute. 2007 99:616-627. doi: 10.1093/jnci/djk133
PMID: 17440163

2019

A Chemical Probe for Tudor Domain Protein Spindlin1 to Investigate Chromatin Function
Fagan V, Johansson C, Gileadi C, Monteiro O, Dunford JE, Nibhani R, Philpott M, Malzahn J, Wells G, Farham R, Cribbs A, Halidi N, Li F, Chau I, Greschik H, Velupillai S, Allali-Hassani A, Bennett JM, Christott T, Giroud C, Lewis AM, Huber KVM, Athanasou N, Bountra C, Jung M, Schüle R, Vedadi M, Arrowsmith CH, Xiong Y, Jin J, Fedorov O, Farnie G, Brennan PE, Oppermann UCT
Journal of Medicinal Chemistry. 2019 62:9008-9025. doi: 10.1021/acs.jmedchem.9b00562
PMID: 31550156

Peptide Hydrogels of Fully-Defined Composition & Mechanics for Probing Cell-Cell & Cell-Matrix Interactions In Vitro
Ashworth J, Thompsona J, Jamesa J, Slatera C, Pijuan-Galitoa S, Lis-Slimaka K, Holleyc R, Mead K, Thompsone A, Arkille K, Tassierif M, Wrightg A, FARNIE G, merry C
Matrix Biology. 2019 . doi: 10.1016/j.matbio.2019.06.009
PMID: 31295578

2018

Target Identification Using Chemical Probes.
Moustakim M, Felce SL, Zaarour N, Farnie G, McCann FE, Brennan PE
Meth. Enzymol.. 2018 610:27-58. doi: 10.1016/bs.mie.2018.09.013
PMID: 30390803

Discovery of a Selective Inhibitor for the YEATS Domains of ENL/AF9.
Christott T, Bennett J, Coxon C, Monteiro O, Giroud C, Beke V, Felce SL, Gamble V, Gileadi C, Poda G, Al-Awar R, Farnie G, Fedorov O
SLAS Discov. 2018 2472555218809904. doi: 10.1177/2472555218809904
PMID: 30359161

Discovery of an MLLT1/3 YEATS Domain Chemical Probe.
Moustakim M, Christott T, Monteiro OP, Bennett J, Giroud C, Ward J, Rogers CM, Smith P, Panagakou I, Saez LD, Felce SL, Gamble V, Gileadi C, Halidi N, Heidenreich D, Chaikuad A, Knapp S, Huber KVM, Farnie G, Heer J, Manevski N, Poda G, Al-Awar R, Dixon DJ, Fedorov O, Brennan P
Angew. Chem. Int. Ed. Engl.. 2018 . doi: 10.1002/anie.201810617
PMID: 30288907

Development of a YEATS-domain chemical probe
Moustakim, M; Monteiro, O; Bennett, J; Giroud, C; Christott, T; Saez, L; Panagakou, I; Felce, L; Gamble, V; Huber, K; Farnie, G; Heer, J; Dixon, D; Brennan, P; Federov, O;
ACS National Meeting Book of Abstracts. 2018 256:-. doi:
PMID:

2017

Targeting IL-1 beta-Wnt signalling to prevent breast cancer colonisation in the bone microenvironment
Eyre, R; Alferez, D; Santiago-Gomez, A; Spence, K; McConnell, J; Simoes, B; Hart, C; Lefley, D; Tulotta, C; Gurney, A; Howell, S; Brown, M; Sims, A; Farnie, G; Ottewell, P; Clarke, R;
Clinical and Experimental Metastasis. 2017 34:493-493. doi:
PMID:

PRMT5 Is a Critical Regulator of Breast Cancer Stem Cell Function via Histone Methylation and FOXP1 Expression.
Chiang, K; Zielinska, AE; Shaaban, AM; Sanchez-Bailon, MP; Jarrold, J; Clarke, TL; Zhang, J; Francis, A; Jones, LJ; Smith, S; Barbash, O; Guccione, E; Farnie, G; Smalley, MJ; Davies, CC;
Cell Reports. 2017 21:3498-3513. doi: 10.1016/j.celrep.2017.11.096
PMID: 29262329

2016

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures.
Morrison, E; Wai, P; Leonidou, A; Bland, P; Khalique, S; Farnie, G; Daley, F; Peck, B; Natrajan, R;
Journal of Visualized Experiments. 2016 :-. doi: 10.3791/54738
PMID: 28060271

Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis.
Eyre, R; Alférez, DG; Spence, K; Kamal, M; Shaw, FL; Simões, BM; Santiago-Gómez, A; Sarmiento-Castro, A; Bramley, M; Absar, M; Saad, Z; Chatterjee, S; Kirwan, C; Gandhi, A; Armstrong, AC; Wardley, AM; O'Brien, CS; Farnie, G; Howell, SJ; Clarke, RB;
Journal of Mammary Gland Biology and Neoplasia. 2016 21:99-109. doi: 10.1007/s10911-016-9361-8
PMID: 27680982

Patient-derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis
Eyre, R; Alférez, DG; Spence, K; Kamal, M; Shaw, FL; Simões, BM; Santiago-Gómez, A; Sarmiento-Castro, A; Bramley, M; Absar, M; Saad, Z; Chatterjee, S; Kirwan, C; Gandhi, A; Armstrong, AC; Wardley, AM; O'Brien, CS; Farnie, G; Howell, SJ; Clarke, RB;
Journal of Mammary Gland Biology and Neoplasia. 2016 21:99-109. doi:
PMID:

Erratum to: Patient-Derived Mammosphere and Xenograft Tumour Initiation Correlates with Progression to Metastasis.
Eyre, R; Alférez, DG; Spence, K; Kamal, M; Shaw, FL; Simões, BM; Santiago-Gómez, A; Sarmiento-Castro, A; Bramley, M; Absar, M; Saad, Z; Chatterjee, S; Kirwan, C; Gandhi, A; Armstrong, AC; Wardley, AM; O'Brien, CS; Farnie, G; Howell, SJ; Clarke, RB;
Journal of Mammary Gland Biology and Neoplasia. 2016 21:111-. doi: 10.1007/s10911-016-9364-5
PMID: 27815673

Three-dimensional modelling identifies novel genetic dependencies associated with breast cancer progression in the isogenic MCF10 model.
Maguire, SL; Peck, B; Wai, PT; Campbell, J; Barker, H; Gulati, A; Daley, F; Vyse, S; Huang, P; Lord, CJ; Farnie, G; Brennan, K; Natrajan, R;
Journal of Pathology. 2016 240:315-328. doi: 10.1002/path.4778
PMID: 27512948

PO-11 - Thrombin and cancer stem-like cells: in vitro support for breast cancer anticoagulation.
Castle, J; Farnie, G; Kirwan, CC;
Thrombosis Research. 2016 :-. doi:
PMID: 27161699

2015

Anti-estrogen Resistance in Human Breast Tumors Is Driven by JAG1-NOTCH4-Dependent Cancer Stem Cell Activity.
Simões, BM; O'Brien, CS; Eyre, R; Silva, A; Yu, L; Sarmiento-Castro, A; Alférez, DG; Spence, K; Santiago-Gómez, A; Chemi, F; Acar, A; Gandhi, A; Howell, A; Brennan, K; Rydén, L; Catalano, S; Andó, S; Gee, J; Ucar, A; Sims, AH; Marangoni, E; Farnie, G; Landberg, G; Howell, SJ; Clarke, RB;
Cell Reports. 2015 12:1968-1977. doi: 10.1016/j.celrep.2015.08.050
PMID: 26387946

Focal adhesion kinase and Wnt signaling regulate human ductal carcinoma in situ stem cell activity and response to radiotherapy.
Williams, KE; Bundred, NJ; Landberg, G; Clarke, RB; Farnie, G;
STEM CELLS. 2015 33:327-341. doi: 10.1002/stem.1843
PMID: 25187396

2014

A differential role for CXCR4 in the regulation of normal versus malignant breast stem cell activity.
Ablett, MP; O'Brien, CS; Sims, AH; Farnie, G; Clarke, RB;
Oncotarget. 2014 5:599-612. doi: 10.18632/oncotarget.1169
PMID: 24583601

Lapatinib inhibits stem/progenitor proliferation in preclinical in vitro models of ductal carcinoma in situ (DCIS).
Farnie, G; Johnson, RL; Williams, KE; Clarke, RB; Bundred, NJ;
Cell Cycle. 2014 13:418-425. doi: 10.4161/cc.27201
PMID: 24247151

2013

Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells.
Singh, JK; Simões, BM; Howell, SJ; Farnie, G; Clarke, RB;
Breast Cancer Research. 2013 15:210-. doi: 10.1186/bcr3436
PMID: 24041156

Targeting CXCR1/2 significantly reduces breast cancer stem cell activity and increases the efficacy of inhibiting HER2 via HER2-dependent and -independent mechanisms.
Singh, JK; Farnie, G; Bundred, NJ; Simões, BM; Shergill, A; Landberg, G; Howell, SJ; Clarke, RB;
Clinical Cancer Research. 2013 19:643-656. doi: 10.1158/1078-0432.CCR-12-1063
PMID: 23149820

2012

A detailed mammosphere assay protocol for the quantification of breast stem cell activity.
Shaw, FL; Harrison, H; Spence, K; Ablett, MP; Simões, BM; Farnie, G; Clarke, RB;
Journal of Mammary Gland Biology and Neoplasia. 2012 17:111-117. doi: 10.1007/s10911-012-9255-3
PMID: 22665270

P-cadherin is coexpressed with CD44 and CD49f and mediates stem cell properties in basal-like breast cancer.
Vieira, AF; Ricardo, S; Ablett, MP; Dionísio, MR; Mendes, N; Albergaria, A; Farnie, G; Gerhard, R; Cameselle-Teijeiro, JF; Seruca, R; Schmitt, F; Schmitt, F; Clarke, RB; Paredes, J;
STEM CELLS. 2012 30:854-864. doi: 10.1002/stem.1075
PMID: 22389315

2011

Breast cancer stem cells and their role in resistance to endocrine therapy.
O'Brien, CS; Farnie, G; Howell, SJ; Clarke, RB;
Hormones and Cancer. 2011 2:91-103. doi: 10.1007/s12672-011-0066-6
PMID: 21761332

2010

Breast cancer stem cells: something out of notching?
Harrison, H; Farnie, G; Brennan, KR; Clarke, RB;
Cancer Research. 2010 70:8973-8976. doi: 10.1158/0008-5472.can-10-1559
PMID: 21045140

Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor.
Harrison, H; Farnie, G; Howell, SJ; Rock, RE; Stylianou, S; Brennan, KR; Bundred, NJ; Clarke, RB;
Cancer Research. 2010 70:709-718. doi: 10.1158/0008-5472.CAN-09-1681
PMID: 20068161

Differentiation therapy: targeting breast cancer stem cells to reduce resistance to radiotherapy and chemotherapy.
Roy, R; Willan, PM; Clarke, R; Farnie, G;
Breast Cancer Research. 2010 12:O5-O5. doi: 10.1186/bcr2496
PMID:

2009

Resistance to endocrine therapy: are breast cancer stem cells the culprits?
O'Brien, CS; Howell, SJ; Farnie, G; Clarke, RB;
Journal of Mammary Gland Biology and Neoplasia. 2009 14:45-54. doi: 10.1007/s10911-009-9115-y
PMID: 19252972

Are stem-like cells responsible for resistance to therapy in breast cancer?
O'Brien, CS; Farnie, G; Howell, SJ; Clarke, RB;
. 2009 :97-109. doi: 10.1007/978-1-4020-8526-0_6
PMID:

2008

Primary ductal carcinoma in situ mammosphere formation: importance of the epidermal growth factor and Notch receptor signalling pathways.
Farnie, G; Spence, K; Brennan, K; Bundred, NJ; Clarke, RB;
Breast Cancer Research. 2008 10:P94-P94. doi: 10.1186/bcr1978
PMID:

Prolactin receptor antagonism reduces the clonogenic capacity of breast cancer cells and potentiates doxorubicin and paclitaxel cytotoxicity.
Howell, SJ; Anderson, E; Hunter, T; Farnie, G; Clarke, RB;
Breast Cancer Research. 2008 10:R68-. doi: 10.1186/bcr2129
PMID: 18681966

Are stem-like cells responsible for resistance to therapy in breast cancer?
O'Brien, CS; Farnie, G; Howell, SJ; Clarke, RB;
Breast Disease. 2008 29:83-89. doi:
PMID: 19029627

2007

Mammary stem cells and breast cancer--role of Notch signalling.
Farnie, G; Clarke, RB;
Stem Cell Reviews and Reports. 2007 3:169-175. doi: 10.1007/s12015-007-0023-5
PMID: 17873349

Breast cancer stem cells: Potential therapeutic targets
Howell, SJ; Farnie, G; Clarke, RB;
Advances in Breast Cancer -London-. 2007 4:51-53. doi:
PMID:

Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways.
Farnie, G; Clarke, RB; Spence, K; Pinnock, N; Brennan, K; Anderson, NG; Bundred, NJ;
JNCI: Journal of the National Cancer Institute. 2007 99:616-627. doi: 10.1093/jnci/djk133
PMID: 17440163

Cyclooxygenase-2 inhibition: effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer.
Barnes, NLP; Warnberg, F; Farnie, G; White, D; Jiang, W; Anderson, E; Bundred, NJ;
British Journal of Cancer. 2007 96:575-582. doi: 10.1038/sj.bjc.6603593
PMID: 17285134

2006

Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold.
Hardcastle, IR; Ahmed, SU; Atkins, H; Farnie, G; Golding, BT; Griffin, RJ; Guyenne, S; Hutton, C; Källblad, P; Kemp, SJ; Kitching, MS; Newell, DR; Norbedo, S; Northen, JS; Reid, RJ; Saravanan, K; Willems, HMG; Lunec, J;
Journal of Medicinal Chemistry. 2006 49:6209-6221. doi: 10.1021/jm0601194
PMID: 17034127

Breast stem cells and cancer.
Farnie, G; Clarke, RB;
. 2006 :141-153. doi:
PMID: 17939300

2005

Isoindolinone-based inhibitors of the MDM2-p53 protein-protein interaction.
Hardcastle, IR; Ahmed, SU; Atkins, H; Calvert, AH; Curtin, NJ; Farnie, G; Golding, BT; Griffin, RJ; Guyenne, S; Hutton, C; Källblad, P; Kemp, SJ; Kitching, MS; Newell, DR; Norbedo, S; Northen, JS; Reid, RJ; Saravanan, K; Willems, HMG; Lunec, J;
Bioorganic and Medicinal Chemistry Letters. 2005 15:1515-1520. doi: 10.1016/j.bmcl.2004.12.061
PMID: 15713419

2004

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