The centrosome is a key cellular organelle, which duplicates once per cell cycle, required to direct formation of the bipolar mitotic spindle during cell division. A correctly assembled mitotic apparatus is required to properly separate replicated sister chromosomes, and defects affecting separation profoundly affect chromosome integrity, leading to genetically instability. Excessive centrosome number termed centrosome amplification (CA: >2 centrosomes per cell) is a characteristic of most human tumours. A common molecular mechanism triggering centrosome amplification is DNA damage, and together they can induce further genomic instability through chromosome missegregation.
Breast Cancer affects 1/8 women (with ~22% mortality) and is categorised clinically into four distinct subtypes; Luminal A, Luminal B, Her2-overexpressing, Triple negative (TNBC:basal/claudin-low). Subtypes differ in disease severity (survival), treatment options (some subtype specific) and clinical outcome. This highlights that an individualised subtype-specific understanding and approach to breast cancer treatment is vital for improving survival rates.
My group investigates the basic molecular mechanisms underpinning how breast tumours adapt to CA including increased genomic instability, structural, and signalling changes. Importantly, we investigate how these molecular changes lead to, and influence tumour invasion and metastases.
My group translates and investigates basic (cell-based) discoveries using breast cancer patient samples (collected at University Hospital Galway). My multi-disciplinary collaborations (including clinical and translational colleagues) allow investigation of how our basic breakthroughs could be applied to improve breast cancer diagnosis or prognosis. Illuminating key pathogenic and molecular mechanisms that underpin the development and spread of breast cancer (centrosome related) is necessary to better understand individual subtypes, and importantly identify new prognostic and therapeutic targets, ultimately with the aim of improving patient outcomes.