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

癌症治疗通常与肝损伤相关，从而导致严重的肝损伤。许多抗癌药物虽然有效，但由于对肝脏的潜在风险，它们被从治疗中撤回，并多次完全退出市场。因此，抗癌新药对肝脏的安全性迫切需要更深层次的了解。在癌症治疗期间，需要仔细监测肝脏损伤，以便继续治疗。然而，临床监测是复杂的，因为肝脏损伤的程度取决于药物的类型、剂量和个人。由于缺乏强有力的生物标志物，目前很难早期发现肝损伤。识别新的生物标记物有助于肝损伤的早期检测和预后，这对所有利益相关者都是有益的。在这方面，最近发现的称为lncRNAs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。我们的工作支持这样的假设，即非编码RNA如lncRNAs可以有效地预测肝损伤。然而，有关lncRNA生物标记物在癌症治疗所致肝损伤中的详细研究尚未开展。本项目的主要目标是确定一个可以作为生物标志物的lncRNA信号，以预测肝脏健康及其对癌症治疗的干扰。该项目将对三种主要的肝细胞类型-肝细胞、胆管细胞和肝窦内皮细胞-使用尖端转录技术。学生将分析转录学数据，以确定可以作为肝脏损伤生物标志物的lncRNAs。此外，使用从患者样本中分离的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。在博士期间接受的培训将帮助候选人在学术界和工业界建立科学生涯。管理团队由Kanhere博士、Goldring教授和Sutton教授组成。首席主管Kanhere博士在基因组学和IncRNA领域拥有多年经验。戈德林教授是生物标志物和肝脏损伤领域的领先专家。这项研究将利用癌症细胞系模型和原始患者样本。除了科学培训外，还有很多机会在科学会议上获得沟通和演讲技能，还有许多出版的机会。重要的是，我们是TransBioLine财团(https://transbioline.com))的成员，该财团将领先的制药行业和学术合作伙伴聚集在一起，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 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的行业合作伙伴之一合作

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 A number of cancer drugs, although effective, are withdrawn from treatment and many times from the market altogether because of potential risk to liver.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