Translational Research in liver oncology
- Postdoctoral Research Fellow
- Hours of work:
- 37.5 hours per week (excluding lunch hours)
- Annual leave:
- 24 days per annum plus statutory days
- C/ Villarroel 170, 08036 BARCELONA
- Accountable to:
- Professor Josep M Llovet
- Up to 3 years, by IDIBAPS
- 38.000 € plus housing facilities
RESEARCH LINE NO LONGER AVAILABLE
A postdoctoral position is available in Professor Josep M Llovet, MD laboratory of Translational research in hepatic oncology. Dr Llovet is at this point leading an international HCC Genomic Consortium recently awarded by the AACR-Landon award, whcin included IDIBAPS (Barcelona), Mt Sinai (New York), Dana-Farber/MIT /Broad Institute (Boston) and National cancer Institute (Milan). This group has recently been awarded with an FP7-Health grant on Genomic predictors and oncogenic drivers in HCC (HEPTROMIC). Dr Llovet has devoted the last 15 years to the research in liver cancer, and is currently combining a double appointment as Professor of Research in IDIBAPS.- Hospital Clínic Barcelona, and Director of HCC Research at Mt Sinai School of Medicine, New York. The position involves working with a team of 7-10 scientists in the Lab in Barcelona studying the molecular pathogenesis of hepatocellular carcinoma, signalling pathways, molecular classification and identification of novel oncogenes as targets for therapies.
The programme is a continuation of work recently published in New England Journal of Medicine (Hoshida et al, 2008), Cancer Research (Chiang et al, 2008), Gastroenterology (Villanueva et al, 2008) and Nature Genetics ( Viswanathan SR, 2009) which has provided critical information on the molecular classification of hepatocellular carcinoma by characterizing the genomic aberrations of the tumoral cells and the microenvironment. In addition, we explored the role of some signal transduction pathways in the pathogenesis of the disease, such as mTOR signalling.
The purpose of this specific programme of work will be to characterize tumor initiating cells along with their gatekeeper events in human liver cancer, and to identify tumor promoting signals in cirrhotic microenvironment. We envision to selectively target pathways involved in tumor development and progression after stratifying patients according to their predicted risk for developing liver cancer. In addition, and once the tumor is established, we will elaborate strategies to identify oncogenic drivers and oncogenic addiction phenomena, and design personalized therapies for both cellular compartments: rapidly proliferating transit-amplifying and terminally differentiated cells.
The project is likely to involve some or all of the following techniques:
- Genome-wide transcriptome analysis 1.1 Whole-genome gene expression analysis will be analyzed by using Whole-Genome DASL assay-Illumina®, a multi-sample BeadChip platform that interrogates more than 24,000 transcripts. We will employ the DNA-mediated Annealing, Selection, extension and Ligation (DASL) assay (Illumina) to profile randomly fragmented mRNA extracted from FFPE tissue (FFPE-RNA). Hybridized arrays will be scanned by BeadArray Reader (Illumina). 1.2 miRNA profiling In order to analyze the global expression profiles of miRNAs it will be used a new plattform BeadChip-Illumina® that measures the levels of 1,146 human microRNAs which cover more than 97% of the miRNAs described in the miRBase database.
- Kinome analysis: High-throughput profiling of phosphorylation status of 62 tyrosine kinases using a bead-based technology (Luminex® 100 IS Total System
- Epigenetic changes. To study the methylation profiling, Methylation Cancer Panel I-Illumina® with the GoldenGate Assay-Illumina® technology will be used. This technology interrogates 1,505 CpG sites in 800 cancer-related genes. A custom-made panel of up to 1,536 loci is also available. The assay consists in the application of a bisulphite treatment to genomic DNA using the EZ-96 DNA Methylation-Gold kit (Zymo Research).
- DNA copy number changes A high-density SNP-array HumanCytoSNP12-Illumina® that interrogates 300,000 SNP markers per sample with a median intermaker distance of 10 Kb will be used. Genomic DNA will be extracted from FFPE samples using QIAamp DNA FFPE Tissue Kit (Qiagen®) by the semi-automated procedure QIAcube®.
- High-density sequencing. To identify novel and low-frequency point mutations the single-template sequencing technology, Human Genome Analyzer, Illumina/Solexa® will be performed. This assay is able to sequence more than 100 Mb of DNA in a single run, allowing the identification of mutations in hundreds of genes simultaneously. The ex tended products are analyzed by SEQUENOM MALDI-TOF mass spectrometry.
- Generation of an oncogenic experimental model: Expression will be mediated by Lentiviral infection. The coding region of each selected oncogenic transforming candidate will be cloned into a lentiviral vector harbouring a reporter GFP gene. Recombinant lentivirus will be produced by co-transfecting using Lipofectamine 2000 human embryonic kidney 293T cells with a) lentiviral-candidate vector or b) empty vector (ViraPower™ Lentiviral Packaging Mix, Invitrogen, Carlsbad, CA). Supernatant containing the lentivirus particles will be collected 48h after transfection and the non-tumorogenic THLE-3 cell line transduced with the lentivirus particles of interest. Gene expression (GFP+) will be evaluated by fluorescence-activated cell sorting (FACS) analysis. Cells exhibiting the highest levels of gene expression will be selected for subsequent analysis.
To conduct translational research investigating a wide range of genomic data obtained from human tissues interrogating SNP array analysis and high density sequencing, whole-genome expression analysis, miRNA analysis, methylation studies and protein studies using cutting edge technology. The post-doc will receive the support of the members of the HCC Genomic Consortium, which integrates around 40 scientists in 3 countries.
To supervise a PhD student, who will contribute to this project.
Duties and Responsabilities
- To contribute to the design and planning of experiments in relation to this project
- To develop a thorough understanding of the research field and be involved in the intellectual decision making process required for successful completion of the project
- To set up and run experiments in consultation with the Principal Investigator
- To record, analyse and write up the results of experiments and ensure that laboratory notebooks are kept fully up to date as a formal record of the research
- To prepare and present findings of research to the Principal Investigator and other members of the centre
- To prepare progress reports on research
- The post holder may be required to perform some limited teaching and/or supervision of other members of staff and/or students, under the guidance of the Principal Investigator
- Responsible for ensuring that designated equipment is safe and maintained in good working order
- As duties and responsibilities change, the job description will be reviewed and amended in consultation with the post holder
- The post holder will carry out any other duties that are within the scope, spirit and purpose of the job, as requested by the Principal Investigator
Knowledge and Qualifications
- Undergraduate degree in a life science discipline.
- PhD in an appropriate life science discipline
- Accredited knowledge and skills in molecular biology, biotechnology and/or bioinformatics
- Proficiency in English language.
- Research stay outside the country of residence.
- Publications in high impact factor peer reviewed journals
- It is expected a thorough background on molecular biology and biotechnology, and a clear interest in molecular biology in oncology. In addition, it will be important to show ability to develop ideas logically and design experiments to test hypotheses, ability to modify and apply new methods to advance a project, and to analyse and write up data for presentations and publications
- The post-doc should have a personal resume showing ability to present complex information effectively to a range of audiences and to write effective written and verbal communication skills.
- Ability to direct junior members of the laboratory in simple laboratory procedures
Experience and Personal Qualities
- Experience of working in a research environment and commitment to high quality research
- Experience in multi-disciplinary working and clear interest in working as part of the team. All the members of the team will collaborate in this research project.
- Ability to work independently and to use own initiative when required.