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 lab is to integrate personalised medicine into clinical practice from a chromosomal instability (CIN) perspective. A better understanding of the biology behind cellular response and resistance to chemotherapy is critical for improving outcomes of patients with cancer. We recently described a non-cell autonomous role for CIN that invoked ER stress, autophagy and lipidomic changes culminating in pro-tumorigenic inflammatory secretion. Overcoming therapy resistance requires a thorough understanding of the mechanisms underlying immune evasion by tumours. We are currently dissecting this via time-lapse microscopy, proteomics, RNA-seq, 3D co-culture, single-cell sequencing and immune phenotyping.
The overarching goal of the lab is to integrate personalised medicine into clinical practice from a chromosomal instability (CIN) perspective. A better understanding of the biology behind cellular response and resistance to chemotherapy is critical for improving outcomes of patients with cancer. We recently described a non-cell autonomous role for CIN that invoked ER stress, autophagy and lipidomic changes culminating in pro-tumorigenic inflammatory secretion. Overcoming therapy resistance requires a thorough understanding of the mechanisms underlying immune evasion by tumours. We are currently dissecting this via time-lapse microscopy, proteomics, RNA-seq, 3D co-culture, single-cell sequencing and immune phenotyping.
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Another focus of research in the lab is studying fundamental cell biological questions in the aging-cancer nexus. Aging is the biggest risk factor for cancer. For instance, a large proportion of breast cancers are diagnosed in post-menopausal women (over the age of 50) with mortality rates set to escalate due to our rapidly-ageing population. Additionally, primary glioblastoma, the most aggressive primary brain tumour, typically appears suddenly in older adults. It has been shown that the aging tumour microenvironment can directly engender a pro-tumorigenic environment over time. We and others have shown non-cell autonomous mechanisms of senescent cells in modulating inflammation via the senescence-associated secretory phenotype (SASP). Aging is accompanied by increased senescence. What are the intrinsic processes that initiate SASP and inflammation during aging? How do CIN-associated alterations in the aging stroma drive tumorigenesis? At the NUHS Centre for Healthy Longevity , we work closely with renowned ageing experts and Directors of CHL, Prof Brian Kennedy and Prof Andrea Maier, and are well-positioned to interrogate these questions as well as explore novel angles in the cancer-aging nexus. It is hoped that these strategies will inform early intervention and treatment strategies in our elderly population.
All Research Projects and Staff are funded by Research grants awarded to Principal Investigator Dr. Karen Crasta.
All Research Projects and Staff are funded by Research grants awarded to Principal Investigator Dr. Karen Crasta.