OUR RESEARCH.How does chromosomal instability lead to tumour development and other age-associated diseases? Why is aging the biggest risk factor for cancer? How do the stroma, immune cells and exosomes participate in ageing-related disease? How do tumours acquire resistance to chemotherapy?
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Our lab seeks to answer these fascinating questions and more!
The overarching goal of the Crasta Lab is to integrate chromosomal instability (CIN)–informed personalised medicine into clinical practice. Despite advances in cancer therapy, resistance to treatment remains a major barrier to durable patient benefit. A deeper understanding of the cellular stress responses and adaptive mechanisms that enable tumour survival under therapeutic pressure is therefore critical for improving cancer outcomes.
Our work has uncovered a previously underappreciated non-cell-autonomous role of chromosomal instability, whereby CIN-expressing cancer cells elicit endoplasmic reticulum stress, autophagy, and lipidomic reprogramming, culminating in a pro-tumorigenic inflammatory secretory state. These findings highlight how stress responses in one cell population can reshape the tumour microenvironment to promote disease progression. Building on this, we seek to understand how CIN-driven signalling contributes to immune evasion and therapy resistance, key obstacles to effective cancer treatment.
To address these questions, we employ an integrated experimental approach combining live-cell time-lapse microscopy, proteomics, RNA sequencing, 3D co-culture systems, single-cell analyses, and immune phenotyping. This multi-scale strategy allows us to dissect dynamic tumour–microenvironment interactions and identify actionable vulnerabilities.
The overarching goal of the Crasta Lab is to integrate chromosomal instability (CIN)–informed personalised medicine into clinical practice. Despite advances in cancer therapy, resistance to treatment remains a major barrier to durable patient benefit. A deeper understanding of the cellular stress responses and adaptive mechanisms that enable tumour survival under therapeutic pressure is therefore critical for improving cancer outcomes.
Our work has uncovered a previously underappreciated non-cell-autonomous role of chromosomal instability, whereby CIN-expressing cancer cells elicit endoplasmic reticulum stress, autophagy, and lipidomic reprogramming, culminating in a pro-tumorigenic inflammatory secretory state. These findings highlight how stress responses in one cell population can reshape the tumour microenvironment to promote disease progression. Building on this, we seek to understand how CIN-driven signalling contributes to immune evasion and therapy resistance, key obstacles to effective cancer treatment.
To address these questions, we employ an integrated experimental approach combining live-cell time-lapse microscopy, proteomics, RNA sequencing, 3D co-culture systems, single-cell analyses, and immune phenotyping. This multi-scale strategy allows us to dissect dynamic tumour–microenvironment interactions and identify actionable vulnerabilities.
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A second major focus of the lab lies at the intersection of ageing and cancer biology. Ageing is the strongest risk factor for cancer, with the majority of malignancies—including breast cancer and primary glioblastoma—arising in older adults. Increasing evidence indicates that the ageing tumour microenvironment itself becomes progressively pro-tumorigenic, in part through the accumulation of senescent cells and chronic inflammation.
We and others have demonstrated that senescent cells exert potent non-cell-autonomous effects through the senescence-associated secretory phenotype (SASP), which can modulate inflammation, tissue architecture, and tumour behaviour. However, fundamental questions remain:
Which intrinsic pathways trigger senescence programs to drive aging-related cancers? How do CIN-associated alterations within the ageing stroma drive tumourigenesis?
Situated within the NUHS Centre for Healthy Longevity, the Crasta Lab is uniquely positioned to interrogate these questions and explore novel conceptual and translational angles at the cancer–ageing nexus. Ultimately, our goal is to inform early intervention strategies and improve therapeutic outcomes in an increasingly ageing population, advancing both cancer care and healthy longevity.
We and others have demonstrated that senescent cells exert potent non-cell-autonomous effects through the senescence-associated secretory phenotype (SASP), which can modulate inflammation, tissue architecture, and tumour behaviour. However, fundamental questions remain:
Which intrinsic pathways trigger senescence programs to drive aging-related cancers? How do CIN-associated alterations within the ageing stroma drive tumourigenesis?
Situated within the NUHS Centre for Healthy Longevity, the Crasta Lab is uniquely positioned to interrogate these questions and explore novel conceptual and translational angles at the cancer–ageing nexus. Ultimately, our goal is to inform early intervention strategies and improve therapeutic outcomes in an increasingly ageing population, advancing both cancer care and healthy longevity.