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3D hydrogel co-culture of MCF10a normal breast cells (Red) with human mammary fibroblasts (Green)
3D hydrogel co-culture of MCF10a normal breast cells (Red) with human mammary fibroblasts (Green)
Changes in viability within increasing hydrogel stiffness in breast cell line cancer progression series.
Changes in viability within increasing hydrogel stiffness in breast cell line cancer progression series.
Growth of primary normal breast ducts in stiffness matched hydrogels with no matrix, matrigel and human ECM mix
Growth of primary normal breast ducts in stiffness matched hydrogels with no matrix, matrigel and human ECM mix

Research groups

Gillian Farnie

PhD


University Research Lecturer and Cellular Assays Group Leader

Biography

Dr 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.  Postdoctoral training at the University of Manchester focused her research on developing novel 3D culture systems to grow human ductal carcinoma in situ (DCIS) and investigating epidermal growth factor and Notch signalling.  During this time she forged a research niche in cancer stem cell (CSC) signalling and was awarded an esteemed 5-year Breast Cancer Now Scientific Fellowship to start her research group. 

Based at the Manchester Cancer Research Centre her research team 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.  Dr Farnie moved to the University of Oxford in 2016 where her team have continued interest in CSC and treatment resistance and are developing novel 3D models to provide a more faithful in vitro environment to study human cancer.  Her team also work in collaboration with the SGC to discover novel targets for drug discovery (Cell Biology Group - SGC Oxford).

Research Areas


Understanding intra-tumour heterogeneity to reveal mechanisms of inherent and induced therapy resistance.

1) CRISPRi druggable library approaches to discover key breast cancer stem cells (CSC) pathways which contribute to treatment resistance in tumours before or during standard of care therapies (anti-endocrine, Chemotherapy, radiotherapy).  The aim is to determine new rational combination therapies with clinical relevance. 

To support these studies we utilise patient samples and patient derived xenografts (PDX) which are key for measuring CSC tumour initiating frequency, the gold standard CSC assay.  In addition we develop in vitro models to recapitulate the patient environment as closely as possible to measure CSCs in their complex tumour microenvironment. 

2) We have developed a unique hydrogel technology which enables independent control of both stiffness and extracellular matrix (ECM) components.  This is a flexible in vitro assay in which we can add multiple cellular components  tumour/epithelium, fibroblasts, immune cells we are exploring the the following;

  • The role of ECM on breast cancer progression, therapy resistance and CSC activity
  • The influence of stiffness and ECM on tumour associated macrophage activity 

Our hydrogel technology is adaptable for many tissue/disease types and we are currently collaborating with groups investigating brain cancers, blood vessel formation, stem cell differentiation and dementia.

3) With our greater understanding of the role of the tumour environment influences treatment response and the growth of immune check point inhibitors, superior human autologous models are needed to replicate patient response.  

We have advanced human tissue raft/ex-plant studies to create an animal free human ex-plant model (of the normal breast and breast cancer) that retains autologous EMC and cancer, stromal and immune cell heterogeneity and over 7 days.  Validations with pre and post treatment biopsies from clinical trials are currently underway for breast cancer prevention, breast and pancreatic cancer. 


GROUP MEMBERS

Ling Felce  - Post-doctoral research assistant - Role of MLLT1 in AML and breast cancer

Carina Gileadi  - Research Assistant - Cell target engagement assays and 3D model screening 

Elizabeth Brown - DPhil Student -  Discovery of new targets for diffuse intrinsic pontine glioma (DIPG)

Pedro Victori Rosa - DPhil Student - computational modelling of 3D tumour heterogeneity

Collaborators

Sacha Howell - Clinical oncologist - University of Manchester

Cathy Merry - Matrix biologist - University of Nottingham

Simon Lord - Clinical Oncologist - University of Oxford

Bryan Welm - Breast Biologist - University of Utah

Francesca Buffa - Computational biologist - University of Oxford

Medicines Discovery Catapult, UK