Investigation of tumour microenvironment in influencing growth in lobular breast cancers

Closing date: 15/03/2027

MB-PhD Studentship: Investigation of tumour microenvironment in influencing growth in lobular breast cancers

Lead Supervisors: Dr Sankari Nagarajan
Lead Supervisors: Dr Sumitra Mohan, Professor Robert Clarke, Dr Andrew Gilmore, Dr Ciara O’ Brien

Applications Deadline: Monday 15th March 2027
Interviews: Week commencing 3rd May 2027
Start date: September 2027

Project Keywords: Lobular breast cancer, fibroblasts, epigenetics 
Research Opportunity: MB-PhD Studentship

Project Outline

Lobular breast cancers represent one of the understudied cancers but of unmet need, due to their poor response to targeted therapies. Failure of drug response is often associated with differential molecular changes in cancer cells according to the origin of the tumour (ductal or lobular), either involving DNA sequences (genetic) or non-DNA-based alterations that affect gene expression (so-called epigenetic alterations). Understanding the coupled genetic and transcriptional reprogramming is critical in revealing the key regulators of treatment response. However, this interactive reprogramming is poorly understood in any cancer, let alone lobular cancers. Moreover, our current knowledge of these cancers includes evidence from in vitro studies that do not adequately replicate patient samples.  

This project aims to understand the previously unknown lobular-specific transcriptional reprogramming influenced by the stromal landscape, by studying gene alterations and gene expression using 3D models, in vivo xenografts and primary tumour tissues. Our study will explore the following: 

  • Identify the influence of stromal factors on lobular cancer growth 
  • Categorise the primary lobular cancer samples with ARID1A expression (loss or presence) 
  • Investigate the mutation-specific stromal and immune landscape and its role in gene and protein expression reprogramming  

Importantly, our comparative analysis with lobular and ductal samples will allow us to identify mechanisms of differential growth response and transcriptional reprogramming, which can indicate potential effective therapeutic approaches.  

The proposed study will utilise a multidisciplinary supervisory team with lot of training opportunities for students in 3D culturing, in vivo assays, spatial imaging, transcriptomics and epigenomics profiling. We successfully obtained access to lobular and ductal tumour samples with matched FFPE and frozen material from Breast Cancer Now Tissue biobank for this study and established the spatial omics protocol directly on lobular cancer samples. This will be an unbiased one-of-a-kind study investigating the interactive transcriptional reprogramming in controlling growth response. 

Applications for this project are now open. Please complete your application on The University of Manchester Postgraduate Application Portal.

About Dr Sankari Nagarajan (project Lead Supervisor)

I am a breast cancer research scientist investigating the transcriptional regulation of disease progression in breast cancers. I completed my Integrated M.Sc. in Bio-Medical Science at Bharathidasan University, Trichy, India. After obtainining a prestigious and competitive PhD scholarship from German Academic Exchange Service (DAAD), I moved to the University of Goettingen, Germany, to work with Prof. Dr. Steven A Johnsen, for my PhD. My successful PhD research on an epigenetic reader protein BRD4 in ER+ breast cancers introduced the possibility of using Bromodomain and Extraterminal domain-containing protein (BET) inhibitors as a therapeutic strategy against breast cancers. This body of work resulted in me being awarded best PhD from my graduate program, Göttingen Graduate Center for Neurosciences, Biophysics, and Molecular Biosciences.

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Headshot of Prof. Sankari Nagarajan

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