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Trained innate immunity in atherosclerosis: interrogating human tissue using state of the art “-omics” approaches


Project Description

Our fundamental approach is to interrogate human tissue (e.g. macrophages laser captured from atherosclerotic plaque or peripheral blood monocytes) using state of the art “-omics” approaches. We typically recreate and validate the findings in the relevant mouse model (with the aid of strong bioinformatics input) and then undertake intervention experiments in mouse (e.g. bone marrow transplant; gene editing) to test our hypothesis using a specific intervention in a validated system.

We intend to expand our programme of work on the metabolic drivers of epigenetic modification in bone marrow cells. We have recently implicated 3 transcription factors in the context of diabetes-induced trained immunity and have plans to further explore both the specific mechanisms and intervention that prevent and reverse these changes. The principal collaborators for this work are in New York (NYU); Boston (Broad Institute); Stockholm (Karolinska).

Training will be given in the relevant areas. We use a variety of techniques and technologies. Day to day: qRT-PCT; Western blotting; exosome extractions and analysis; laser capture microdissection; FACS; Seahorse metabolic analyses; immunofluorescence. We outsource RNA sequencing; ATAC seq and ChIP seq, but are actively involved in the interpretation of data by our bioinformatician. It is common in this laboratory to import specific techniques / collaborations to address a given experiment. All our students to date have been awarded their doctorate. Our students’ work is often recognised by prizes and awards and national and international meetings.

As well as the specific training detailed above, students will have access to high-quality training in scientific and generic skills, as well as access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

Funding Notes

Our main deadline for applications for funded places has now passed. Supervisors may still be able to consider applications from students who have alternative means of funding (for example, charitable funding, clinical fellows or applicants with funding from a foreign government or equivalent). Prospective applicants are strongly advised to contact their prospective supervisor in advance of making an application.

Please note that any applications received after the main funding deadline will not be assessed until all applications that were received by the deadline have been processed. This may affect supervisor availability.

References

Akbar N, ….Choudhury RP. Endothelium-derived extracellular vesicles promote splenic monocyte mobilization in myocardial infarction. JCI Insight. 2017 Sep 7;2(17). pii: 93344. doi: 10.1172/jci.insight.93344.
Ruparelia N, Chai JT, Fisher EA, Choudhury RP. Inflammatory processes in cardiovascular disease: a route to targeted therapies.Nat Rev Cardiol. 2017 Mar;14(3):133-144. doi: 10.1038/nrcardio.2016.185. Review.
Ruparelia N, …Choudhury RP. Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans. Eur Heart J. 2015 Aug 1;36(29):1923-34. doi: 10.1093/eurheartj/ehv195. Epub 2015 May 16.
Cahill TJ, Choudhury RP, Riley PR. Heart regeneration and repair after myocardial infarction: translational opportunities for novel therapeutics.Nat Rev Drug Discov. 2017 Oct;16(10):699-717. doi: 10.1038/nrd.2017.106. Review.
Chai, JT….Choudhury RP.Differential Gene Expression in Macrophages From Human Atherosclerotic Plaques Shows Convergence on Pathways Implicated by Genome-Wide Association Study Risk Variants. Arteriosclr Thromb Vasc Biol 2018. In press
McAteer MA, … Choudhury RP. In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide. Nat Med. 2007 Oct;13(10):1253-8. Epub 2007 Sep 23.

Related Subjects

How good is research at University of Oxford in Clinical Medicine?

FTE Category A staff submitted: 238.51

Research output data provided by the Research Excellence Framework (REF)

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