Non-coding RNA biomarkers to predict liver injury during cancer therapy

癌症治疗通常伴随着肝损伤，导致严重的肝损伤。许多抗癌药物虽然有效，但由于对肝脏有潜在的风险，它们被从治疗中撤出，并多次完全退出市场。因此，新型抗癌药物的肝脏安全性迫切需要更深入的认识。在癌症治疗期间，肝损伤需要仔细监测以继续治疗。然而，临床监测是复杂的，因为肝损伤的程度取决于药物的类型、剂量和个人。由于缺乏可靠的生物标志物，目前很难早期发现肝损伤。需要鉴定新的生物标志物，可用于肝损伤的早期检测和预后，并将有利于所有利益相关者。在这方面，最近发现的称为lncrna的新型rna不编码蛋白质，为我们提供了大量可能的生物标志物。我们的工作支持了非编码rna如lncrna可以有效预测肝损伤的假设。然而，lncRNA生物标志物在癌症治疗肝损伤中的详细研究尚未开展。本项目的主要目的是鉴定一个lncRNA标记，该标记可以用作预测肝脏健康及其对癌症治疗的干扰的生物标志物。该项目将对三种主要的肝细胞类型——肝细胞、胆管细胞、肝窦内皮细胞——采用尖端的转录组学。该学生将分析转录组学数据，以识别可以作为肝损伤生物标志物的lncrna。此外，使用来自患者样本的分离细胞和一组相关的癌症药物，候选人将进行时间过程和剂量反应，以确定lncRNA对药物毒性的反应，最终可转化为患者治疗。这是一个在多学科环境中工作的独特机会。在博士期间获得的培训将有助于候选人在学术界和工业界建立科学事业。监督小组由Kanhere博士、Goldring教授和Sutton教授组成。主要负责人Kanhere博士在基因组学和lncRNA领域有多年的经验。Goldring教授是生物标志物和肝损伤领域的权威专家。该研究将利用癌细胞系模型和主要患者样本。除了科学训练之外，还有充分的机会在科学会议上获得交流和演讲技巧，并有许多发表文章的机会。重要的是，我们是TransBioLine联盟（https://transbioline.com）的一部分，该联盟汇集了领先的制药行业和学术合作伙伴，以确定可以可靠地预测包括肝脏在内的不同器官损伤的生物标志物。学生极有可能有机会与TransBioLine联盟的一个行业合作伙伴一起工作。参考资料：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022221/https://pubmed.ncbi.nlm.nih.gov/21925379/https://pubmed.ncbi.nlm.nih.gov/33622496/https://pubmed.ncbi.nlm.nih.gov/34510227/https://transbioline.comhttps://twitter.com/Kanhere_lab

Cancer treatment is often associated with liver injury leading to severe liver damage. A number of cancer drugs, although effective, are withdrawn from treatment and many times from the market altogether because of potential risk to liver. Hepatic safety of new cancer drugs therefore urgently requires a deeper understanding. During cancer therapy, liver injury needs to be carefully monitored for continued treatment. However, clinical monitoring is complicated as the extent of liver injuries vary depending on the type of drug, dosage and individuals. Early detection of liver injury is currently difficult because of lack of robust biomarkers. Identification of new biomarkers that can be useful for early detection and prognosis of liver injury are required and will be beneficial to all stakeholders. In this regard, recent discovery of novel RNAs called lncRNAs, that do not code for proteins, have presented us with a large repertoire of possible biomarkers. Our work supports the hypothesis that non-coding RNAs such as lncRNAs can be effective in prediction of liver injury. However, detailed investigation of lncRNA biomarkers in cancer treatment induced liver injury has not been carried out. The main objective of this project is to identify a lncRNA signature which can be used as biomarkers to predict liver health and its perturbation on cancer therapy. The project will employ cutting-edge transcriptomics on three major liver cell types - hepatocytes, cholangiocytes, liver sinusoidal endothelial cells. The student will analyse transcriptomics data to identify lncRNAs that can act as biomarkers of liver injury. In addition, using isolated cells from patient-derived samples and a panel of relevant cancer drugs, the candidate will conduct time-courses and dose-response to ascertain lncRNA response to drug toxicity which can be eventually translated to patient treatment. This is an unique opportunity to work in a multi-disciplinary environment. Training gained during this PhD will help the candidate to establish a scientific career in academia as well as industry.The supervisory team consists of Dr Kanhere, Prof Goldring and Prof Sutton. Primary supervisor, Dr Kanhere, has many years of experience in genomics and lncRNA field. Prof Goldring is a leading expert in the field of biomarkers and liver injury. The study will utilise cancer cell line models and primary patient samples. In addition to scientific training, there is ample opportunity to acquire communication and presentation skills at scientific meetings and many opportunities for publications. Importantly, we are part of TransBioLine consortium (https://transbioline.com) which brings together leading pharmaceutical industries and academic partners to identify biomarkers that can reliably predict injuries to different organs including liver. It is highly likely that the student will have an opportunity to work with one of the industry partners from TransBioLine consortium.References:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022221/https://pubmed.ncbi.nlm.nih.gov/21925379/https://pubmed.ncbi.nlm.nih.gov/33622496/https://pubmed.ncbi.nlm.nih.gov/34510227/https://transbioline.comhttps://twitter.com/Kanhere_lab