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  • Ellie Tzima

about the research

Our arteries are exposed to various types of blood flow depending on their shape. When blood flow is turbulent, endothelial cells that line arteries become inflamed and activated, resulting in chronic inflammation and development of atherosclerotic plaques. These plaques can obstruct blood flow to the heart or brain and cause heart attacks or strokes. The mechanisms by which endothelial cells sense and respond to turbulent blood flow are a mystery. Work from our group has identified specialised receptors expressed on the surface of cells whose function is to detect blood flow and send signals that ultimately result in disease. One of these receptors is called Plexin D1. We now aim to understand in greater detail the mechanism by which Plexin D1 senses blood flow and how it signals to other cells to form a plaque. The student will have the opportunity to carry out both basic and translational research using a multi-disciplinary approach that include both in vitro and in vivo approaches in a highly collaborative and supportive environment.

 Additional supervision will be provided by Associate Professor John Reader and Dr Vedanta Mehta.

training opportunities

This DPhil will be based at the Tzima group at the Wellcome Trust Centre for Human Genetics. We are part of a wider scientific community with expertise in cardiovascular biology and the opportunity to be co-mentored and co-supervised by other senior scientists will be made available.  The student will have the opportunity to be exposed to a wide range of techniques based on the student’s individual interests that include: i) use of imaging and genetic approaches to characterize how mechanosensing affects disease intitiation and progression ; (2) applying high throughput RNA sequencing and proteomics approaches to globally dissect steps involved in disease aetiology; 3) use of bioinformatics and biochemical experimental approaches to understand the role of blood flow forces in cardiovascular disease

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have 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.

publications

1

Mehta V, Pang K, Rozbesky D, Nather K, Keen A, Lachowski D, Kong Y, Karia D, Ameismeier M, Huang J, Fang Y, Hernandez A, Reader JS, Jones EY, Tzima E. The Guidance Receptor Plexin D1 moonlights as an endothelial mechanosensor. 2020 Nature 578:290-295

2

Mehta V, Pang KL, Givens CS, Chen Z, Huang J, Sweet DT, Jo H, Reader JS and Tzima E.

Mechanical forces regulate endothelial-to-mesenchymal transition and atherosclerosis via an Alk5-Shc mechanotransduction pathway. Science Advances. 2021; (28):eabg5060

 

3

Douglas G, Mehta V, Al Haj Zen A, Akoumianakis I, Goel A, Rashbrook V, Trelfa L, Donovan L, Drydale E, Chuaiphichai S, Antoniades C, Watkins, H, Kyriakou#Tzima E# and Channon K#.  A key role for the novel coronary artery disease 1 gene JCAD in atherosclerosis via shear stress mechanotransduction. 2019. Cardiov. Res. Oct 4

https://pubmed.ncbi.nlm.nih.gov/31584065

4

Liu Y, Collins C, Kiosses WB, Murray AM, Joshi M, Shepherd TR, Fuentes EJ, Tzima E. 2013. A novel pathway spatiotemporally activates Rac1 and redox signaling in response to fluid shear stress. J. Cell Biol.,  201 (6), pp. 863-73. –

http://www.ncbi.nlm.nih.gov/pubmed/23733346

5

Mehta V, Tzima E. Cardiovascular disease: A turbulent path to plaque formation. Nature. 2016;540(7634):531-532. 

6

Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA. 2005. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature,  437 (7057), pp. 426-31. - http://www.ncbi.nlm.nih.gov/pubmed/16163360