LICAMM Breaking the Barrier: Endothelial Dysfunction in Diabetes and Heart Failure

Endothelial cells are central regulators of vascular health, controlling blood flow, vessel tone, barrier integrity, and interactions with circulating immune cells. In diseases such as diabetes and heart failure, endothelial cells may contribute to myocardial and skeletal muscle dysfunction by cell-cell cross talk and by influencing nutrient delivery, inflammation and tissue remodelling. The presence of type 2 diabetes increases the complexity and severity of heart failure, leading to increase mortality. Importantly, despite the integral role for endothelial cells, the differences in endothelial biology between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), particularly in the presence or absence of diabetes, remain poorly understood.

<p>The fellow will investigate how endothelial cells function and signalling pathways are altered in heart failure with and without diabetes. The student will use a combination of experimental systems, including animal disease models, established endothelial cell lines, and patient-derived endothelial cells. Approaches will include bulk and single cell RNA sequencing to define transcriptional reprogramming, microfluidic assays to model blood flow and shear stress, and co-culture systems to explore interactions between endothelial cells and leukocytes. Additional molecular, imaging, and functional assays will be applied to assess endothelial barrier function, signalling pathways, and inflammatory activation.</p> <p>The project offers training in cutting-edge methods spanning cell and molecular biology, bioinformatics, and translational vascular research. The student will develop skills in experimental design, data analysis, and interdisciplinary collaboration in an environment that bridges fundamental discovery and clinically relevant questions. This project will particularly suit a motivated student interested in cardiovascular biology, metabolism, and mechanisms of vascular disease.</p> <h5>References</h5> <ol> <li>Drozd M, Bruns AF, Yuldasheva NY, Maqbool A, Viswambharan H, Skromna A, Makava N, Cheng CW, Sukumar P, Eades L, Walker AMN, Griffin KJ, Galloway S, Watt NT, Haywood N, Palin V, Warmke N, Imrie H, Bridge K, Beech DJ, Wheatcroft SB, Kearney MT, Cubbon RM. Endothelial insulin-like growth factor-1 signalling regulates vascular barrier function and atherogenesis. Cardiovasc Res. 2025 Jul 8;121(7):1108-1120. doi: 10.1093/cvr/cvaf055. PMID: 40171617; PMCID: PMC12236071.</li> <li>Meakin PJ, Coull BM, Tuharska Z, McCaffery C, Akoumianakis I, Antoniades C, Brown J, Griffin KJ, Platt F, Ozber CH, Yuldasheva NY, Makava N, Skromna A, Prescott A, McNeilly AD, Siddiqui M, Palmer CN, Khan F, Ashford ML. Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction. J Clin Invest. 2020 Aug 3;130(8):4104-4117. doi: 10.1172/JCI122237. PMID: 32407295; PMCID: PMC7410081.</li> </ol>

<p>Please note these are not standalone projects and applicants must apply to the PhD academy directly.</p> <p>Applications can be made at any time. You should complete an <a href="https://medicinehealth.leeds.ac.uk/faculty-graduate-school/doc/apply-2">online application form</a> and attach the following documentation to support your application. </p> <ul> <li>a full academic CV</li> <li>degree certificate and transcripts of marks (or marks so far if still studying)</li> <li>Evidence that you meet the programme’s minimum English language requirements (if applicable, see requirement below)</li> <li>Evidence of funding to support your studies</li> </ul> <p>To help us identify that you are applying for this project please ensure you provide the following information on your application form;</p> <ul> <li>Select PhD in Medicine, Health & Human Disease as your planned programme of study</li> <li>Give the full project title and name the supervisors listed in this advert</li> </ul>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree.

Applicants whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study. The minimum requirements for this programme in IELTS and TOEFL tests are: • British Council IELTS - score of 7.0 overall, with no element less than 6.5 • Internet Based TOEFL - overall score of 95 with not less than 22 in listening, 22 in reading, 24 in speaking and 22 in writing. Tests must be taken at a test centre.

<p>For further information please contact the Faculty Admissions Team:<br /> e:<a href="mailto:fmhpgradmissions@leeds.ac.uk">fmhpgradmissions@leeds.ac.uk</a></p>