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Single Cell Cancer Genomics Laboratory

Laboratory overview

Our primary research goal is to understand how individual cells contribute to the epigenetic and genetic landscape of a tumour. Through this we can better understand cancer etiology and identify novel biomarkers for the diagnosis and treatment of patients with cancer.

With single-cell genomics, we can now look at every single cell in a tumour made up of millions of cells and identify exactly which cell or cells have caused the tumour and which ones are resistant to treatment. We can learn what happened to the DNA of those cells that turned them from normal, healthy cells into cancerous ones. Dr Bhupinder Pal, Head, Single Cell Cancer Genomics Laboratory
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Our focus

Understanding cancer at a single cell level in order to advance cancer biomarker discovery and translation

My laboratory specialises in using innovative single cell techniques to deconstruct tissue samples and reveal the genetic architecture of individual cells. This will allow us to study heterogeneity in different cancers, including breast cancer, and address key biological questions:

  • How does intra-tumoural molecular and cellular heterogeneity drive tumour progression and metastasis in aggressive cancers?
  • What role do the immune and stromal microenvironments play during tumorigenesis?
  • What premalignant molecular alterations are involved in familial cancers and can rare aberrant cell populations be identified for their detection and treatment?

Utilising single-cell genomics to understand treatment resistance 

Molecular heterogeneity in cancer cells and the tumour microenvironment is one of the key driving factors in drug resistance and cancer relapse. To address this urgent clinical need, our research team is keen to:

  • Use integrated single-cell approaches to monitor transcriptome or epigenetic changes and map acquired mutations associated with the cancer microenvironment during treatment.
  • Test cellular specificity of novel anti-cancer therapies through utilising patient-derived xenografts (PDXs) as pre-clinical models.

To achieve these objectives, my laboratory is focusing on developing new and improved tools and methods to study low cell numbers and single cells.

 

Quick facts

Epigenetics

Cells can manipulate genetic information via a process known as epigenetic regulation, which involves the masking and unmasking of DNA without altering its genes or genetic code. Epigenetic mechanisms have been found to be responsible for controlling the activity of genes responsible for initiating or suppressing cancer.

Tumour micro-environment

A tumour microenvironment is created by a dynamic micro-community of cancer cells and surrounding blood, immune, fibroblast, and fat cells. Interactions between resident cell types can influence tumour progression and patient response to cancer treatment.







  1. Fu NY, Pal B, Chen Y, et al. (2018) Foxp1 Is Indispensable for Ductal Morphogenesis and Controls the Exit of Mammary Stem Cells from Quiescence. Dev Cell. Dec 3;47(5):629-644.e8.
  2. Pal B, Chen Y, Vaillant F et al. (2017) Construction of developmental lineage relationships in themammary gland by single-cell RNA profiling. Nature Communications Nov 20;8(1):1627
  3. This is the first description of single-cell RNA profiling of mouse mammary epithelial cells spanning four developmental stages in the post-natal gland. A large–scale shift in gene expression from a relatively homogeneous basal-like program in pre-puberty was revealed. A novel progenitor subset, marked by CD55, a luminal transit population, and a rare mixed-lineage cluster, was also uncovered.

  4. Nolan E, Vaillant F, Branstetter D, Pal B et al. (2016). “RANK ligand as a potential target for breast cancer prevention in BRCA1 mutation carriers”. Nature Medicine. Aug;22(8):933-9 
  5. Pal B et al. (2015) "Integration of microRNA signatures of distinct mammary epithelial cell types with their gene expression and epigenetic portraits". Breast Cancer Research. Jun18. 17; 85.
  6. This work describes the relationship between microRNA and target mRNA expression profiles of mouse and human mammary epithelial subsets. The role of histone H3 modifications in regulating the expression of mammary specific miRNA was also revealed for the first time. Among the top 10 most highly accessed articles of 2015.

  7. Pal B, et al. (2013) Global changes in the mammary epigenome are induced by hormonal cues and coordinated by Ezh2. Cell Reports 3(2), 411-26.
  8. The first description of the mammary epigenome and its responsiveness to the steroid hormone progesterone, with important implications for progestin-induced cancer and chemoprevention. The key histone methylase Ezh2 is a potential therapeutic target in breast cancer. The ChIPseq technique was employed on 100-200K cells to map histone H3 modifications.

Meet our team

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