英国肝脏研究基金会（FLR）博士后职位—癌症免疫学

英国肝脏研究基金会（FLR）博士后职位—癌症免疫学

Post-doctoral Scientist in Cancer Immunology

Foundation for Liver Research – Liver Regeneration & Tissue Engineering, & Liver Immunology Group

Group Liver Regeneration & Tissue Engineering, & Liver Immunology

Reporting to Dr Luca Urbani (PI) and Prof Shilpa Chokshi (PI & Chief Scientific Officer)

Duration 2 years initially

Annual leave 27 days per annum

Starting date July – August 2024

CLOSING DATE FOR APPLICATIONS: 9am Monday 1st July 2024

The Role

The Foundation for Liver Research (FLR) is seeking an enthusiastic and motivated post-doctoral scientist to join a cross-disciplinary project with the Liver Regeneration and Tissue Engineering group and the Liver Immunology group. As a post-doctoral scientist, you will play a crucial role in a project investigating the immunomodulatory properties of the extracellular matrix (ECM) in hepatocellular carcinoma and other liver cancers. Your work will focus on the interactions between immune cells and ECM-associated proteins.

Who we are:

The FLR was established in 1974 to develop and extend research into diseases of the human liver. For over 30 years the FLR has supported ground-breaking research programmes, including the early pioneering work at King’s College Hospital into liver transplantation and acute liver failure, under the direction of Professor Roger Williams. Since 2016 research has taken place within the purpose-built Institute of Hepatology, recently renamed the Roger Williams Institute of Hepatology (RW-IoH) which provides laboratory space for up to 65 research staff.  The translational research strategy aims ‘To support fundamental scientific research that brings clinical benefits for patients with liver disease’. The competitive research portfolio encompasses the common aetio-specific clinical manifestations of liver disease under the heading of ‘Mechanisms of Hepatic Injury and Repair’ with interconnected workstreams that are underpinned by a common cross-cutting theme of inflammation and immune dysfunction. Areas of research include Fibrosis/Cirrhosis, Tissue Engineering, Regenerative Medicine, Viral Hepatitis, Liver Cancers, MASLD and Alcohol-related Liver Disease. The studies are dedicated to the discovery and creation of innovative drug targets and biomarkers to address the complex challenges associated with treating Liver Disorders. The FLR is also involved in a number of international research programmes and scientific meetings. Further information can be obtained at:  http://www.liver-research.org.uk .  The RW-IoH operates as an independent research organisation in partnership with King’s College London, with close research links with King’s College Hospital and access to clinical material.

Project Overview:

Join us in a groundbreaking research project aimed at studying the intricate crosstalk between immune cells and the extracellular matrix (ECM) in primary (hepatocellular carcinoma, HCC) and secondary (colon cancer metastases) liver cancer. Using patient-derived cells and ECM extracts, this project seeks to unravel how the tumour microenvironment's extracellular compartment modulates anti-tumour immunity.

Why This Project Matters:

Cutting-Edge Research: Be at the forefront of cancer research, exploring novel aspects of the tumour microenvironment and its role in cancer progression and treatment resistance.

Real-World Impact: Contribute to understanding critical mechanisms that could lead to improved therapies and outcomes for liver cancer patients.

Collaborative Effort: Work with a multidisciplinary team of experts, leveraging state-of-the-art facilities and methodologies to drive meaningful advancements in cancer research.

Why Join Us?

Collaborative Environment: Work with an integrated team of dedicated scientists and researchers.

Impactful Work: Contribute to research with strong potential to improve cancer therapies.

Professional Growth: Enhance your skills and knowledge in a supportive environment.

Key Objectives of the project:

Explore the complex interactions between the tumour microenvironment (TME) and cancer cells, focusing on tumour development, progression, and drug resistance.

the role of the ECM, a dynamic web of molecules providing structural support and biochemical cues, fundamental in various tissue processes.

Examine the profound remodelling of the liver ECM in liver cancer, which influences cell behaviour, tumour progression, metastatic dissemination, and immune cell function.

Determine the impact of tumour-specific ECM proteins on anti-tumour immune responses, a largely unexplored area with significant therapeutic potential.

Delve into the potential of ECM to influence immunotherapy outcomes, particularly checkpoint receptor inhibition (CRI).

Investigate why only 20% of HCC patients respond to CRI and why many become resistant or refractory after an initial response, focusing on the role of the ECM in these phenomena.

Key Responsibilities:

Project Management: Handling the day-to-day management and coordination of the project.

Research Excellence: Conduct research that integrates immunology and tissue engineering.

Collaboration: Work closely with local, national and international experts in liver regeneration and immunology.

Innovation: Develop novel insights into liver cancer treatment.

Project Planning and Delivery: Plan and organise experimental procedures, ensuring efficient and effective project execution.

Technical Support: Assist with lab organisation, conduct research experiments, collect and analyse data, review scientific literature, and write reports and manuscripts for publication.

Research Presentations: Present research findings at internal and national/international scientific meetings and conferences.

Point of Contact: Serve as the primary contact for staff and students regarding experimental procedures and techniques within the research area.

Mentorship and Supervision: Mentor and supervise junior research team members and visiting students, providing guidance and support for their professional development.

Key research activities:

The post holder will be responsible for the following key research activities:

Expanded Co-culture Experiments: We will perform co-culture experiments with a larger cohort of patient samples. Identified pathways will be further investigated using in vitro hepatic stellate cells or CAF-derived ECM in the context of immunotherapies.

Mechanistic Studies: Examine how immune cells interact with remodelled tumour ECM, using established protocols to better understand these mechanisms.

Advanced Techniques: Characterise immune cell responses using techniques such as FACS, Luminex, T cell proliferation assays, proteomics, spatial transcriptomics, and more.

Correlation with Clinical Data: Correlate in vitro findings with in vivo and clinical data to validate our results.

Training will be available and there will be opportunity for the post holder to develop his/her/their own interests within the scope of the project.

What would make you a good fit for the role?

PhD in immunology, cancer immunology, or cancer matrix biology.

Research Experience in

Solid cancer microenvironment studies.

Isolation, culture and analysis of human immune cells.

Cell culture and molecular biology techniques.

Molecular immunology techniques.

DNA, RNA, and protein assays.

Technical Expertise:

In-depth experience in Flow Cytometry.

Laboratory-based experience in fluorescence microscopy and immunofluorescence protocols.

Professional Skills:

Excellent organisational skills with the ability to work independently.

Proven ability to prepare data for publication, including statistical analysis.

Experience in cross-discipline collaboration.

Proven ability to work with colleagues and initiate multi-disciplinary projects.

Good publication record in cancer immunology in peer-reviewed journals.

Communication and Interpersonal Skills:

Ability to present complex ideas simply at internal, national, and international meetings.

Excellent written communication skills in English.

Good interpersonal skills, demonstrating the ability to establish and maintain effective working relationships with students, staff, peers, and management.

Commitment to Safety: Strong commitment to health and safety standards in the laboratory.

Desirable skills

Experience of working with ECM, Biomaterials and/or decellularisation techniques

Previous experience and success in writing research grants proposals

To apply: send a 1-page covering letter explaining your background and suitability for our team, together with a detailed CV describing your research experience to date and including names and contact details of two referees, one of whom is the current/most recent employer to James Poynton, Chief Operating Officer, Foundation for Liver Research: j.poynton@researchinliver.org.uk.  Please name documents you send as follows:.

For informal enquiries contact Dr Luca Urbani, Principal Investigator:  luca.urbani@researchinliver.org.uk. Invitations for interview will be communicated by email.

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