Job title: Postdoctoral Fellow – J. M. Adrover lab

Reporting to: Jose M. Adrover, Group Leader

Contact term: This is a full-time, fixed term (4-year) position on Crick terms and conditions of employment.

The Lab

Dr. Adrover’s laboratory focuses on how cancer affects whole-body physiology, with a particular emphasis on the cardiovascular, haematopoietic, and immune systems.

Cancer is a highly complex disease, and tumour progression requires the concerted action (and inaction) of many physiological systems. To survive, tumours co-opt, modulate, and alter many different biological processes, both locally in the tumour microenvironmental ecosystem and broadly in the whole organism, the “macroenvironment” of cancer. In doing so, however, cancer affects normal physiology in ways that are detrimental to the welfare of (and that often result in fatal outcomes for) cancer patients.

A prime example of that is the abnormally elevated burden of cardiovascular disease that cancer patients endure. There is a known clinical correlation between cancer and cardiovascular disease. For instance, lung cancer patients have a 90% increase in the risk of coronary artery disease, and over 66% increased risk of cardiovascular disease overall in comparison to the general population. But we still don’t fully understand why this happens and, most importantly, how can we protect cancer patients and cancer survivors from this burden. Understanding these critical unknowns is one of the main efforts of our laboratory.

A second example of how cancer as a systemic disease remotely affects other normal physiological processes is the changes that cancer imposes on the haematopoietic system. This is still not well understood but it can shift the production of different immune cells towards states that favour the growth and dissemination of the tumour. These same changes can also cause other problems for cancer patients, including some that will affect cardiovascular health. We recently found that cancer induces the appearance of a previously unknown subpopulation of neutrophils (vascular-restricted neutrophils or vrPMNs). They have enhanced NET-formation ability and are unable to extravasate towards inflammatory stimuli, so they seem to be stuck inside the vasculature. These cells can form intravascular aggregates and NETs inside the tumour microvasculature leading to the blockade of blood flow and the subsequent hypoxia and necrosis of downstream vascular regions. Paradoxically, this leads to worse prognosis for cancer patients, as it enhances the metastatic capacity of the tumours. We believe that this population can also explain the elevated burden of cardiovascular disease on cancer patients, and the goal of this project will be to study how the tumour induces the appearance of these vascular-reactive neutrophils, how they affect the outcome of cardiovascular disease, and how can we control them to help cancer patients.

Project summary

The Cancer Macroenvironment Lab is seeking applications for postdoctoral candidates to carry out experimental work aimed at understanding the interplay between cancer as a systemic disease and cardiovascular disease. The research program will study how cancer affects the haematopoietic stem cell compartment to induce changes in myeloid populations that can explain the abnormally elevated cardiovascular disease of cancer patients.

In this project, some of the specific aims include but are not limited to:

• Using murine models of cancer to analyse the hematopoietic stem and progenitor cell compartment in the bone marrow to understand how the tumour induces changes in neutrophil phenotypes and functions.
• Interrogating the role of neutrophils and other innate immune populations in murine models of cardiovascular disease, including models of thrombosis and acute myocardial infarction, to dissect the role of cancer-imposed changes to the immune compartment in cardiovascular disease outcome.
• Using state of the art in vivo intravital imaging techniques to study the intravascular behaviour of neutrophils in tumour-bearing mice.

Postdoctoral Fellows will lead their own projects, contribute to other projects on a collaborative basis (both in the lab and with external collaborators) and may guide PhD students in their research. The ability to work in a team is essential.

Key experience and competencies

The post holder should embody and demonstrate our core Crick values: bold, open, and collegial. The applicant should have experience with basic science work that has resulted in first author publications (already published or in the process of being published). This position is funded by the laboratory’s Crick core funding, but the applicant will be encouraged to apply for fellowships.

Essential

• PhD in immunology, cancer biology, biochemistry or cell biology or in the final stages of PhD submission
• Knowledge and experience in immunology or cancer biology
• Technical expertise in mouse work and microscopy, and experience with experimental design
• Track record of writing papers as evidenced by publications or submitted manuscripts in peer-reviewed journals
• Evidence of data presentation at scientific meetings
• Ability to work independently and collaborate with others

Desirable

• Experience in cancer, haematopoiesis or immunology research
• Experience in models of cardiovascular disease
• Experience in intravital microscopy

About Us

At the Crick, we conduct research at the forefront of biomedical research. We combine rigour with an open and collaborative culture, and are outward-looking, reflecting our status as a partnership of six organisations aiming to pool knowledge, ideas and resources.

We have a wide research portfolio with no divisions or departments, bringing biomedical researchers together with clinicians, physical scientists and applied scientists from our pharmaceutical partners.

We aim to attract the most talented researchers and support them to tackle innovative research questions. Our science technology platforms provide our researchers with access to state-of-the-art technology and expertise.

We provide an excellent learning environment with dedicated education programmes in public engagement with science, education and personal development, and a postdoc training programme that prepares scientists for leadership roles in science.

• If you are interested in applying for this role, please apply via our website.
• All offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom.
• If you require a visa to work in the UK we will help support your application should you be successful

Equality, Diversity & Inclusion

We welcome applications from all backgrounds. We are committed to providing equal employment opportunities, regardless of ethnicity, nationality, gender, sexual orientation, gender identity, religion, pregnancy, age, disability, or civil partnership, marital or family status. We particularly welcome applications from people who are Minority Ethnic as they are currently underrepresented in the Crick at this level.

Diversity is essential to excellence in scientific endeavour. It increases breadth and perspective, leading to more innovation and creativity. We want the Crick to be a place where everyone feels valued and where diversity is celebrated and seen as part of the foundation for our Institute’s success.

The Crick is committed to creating equality of opportunity and promoting diversity and inclusivity. We all share in the responsibility to actively promote dignity, respect, inclusivity and equal treatment and it is our aim to ensure that these principles are reflected and implemented in all strategies, policies and practices.