High blood pressure evolving into hypertension and potentially heart failure occurs excessively in African-Caribbean-(AfC) and directly sub-Saharan-origin (Af) women. Curiously, hypertension is significantly associated with (i.e. coincides more frequently than expected) with uterine fibroids and keloid scars, both also excessive in these populations. The origin or causes of such excess, and their excess coincidence, is unknown. We hypothesize that uterine fibroids and keloid share molecular mechanisms of fibrosis with small vessel, aortic and myocardial fibrosis, underlying their links with hypertension.
To test this hypothesis, this PhD project will study fresh and stored tissues from patients with these conditions using cell culture, advanced microscopy, -omic/bioinfomatic methods as well as help in clinical testing (e.g. cardiac MRI), contributing to an entirely new angle for the origins of heart failure in under-served populations with high disease burdens.
Aims:
1. Characterise the cellular and molecular commonalities/differences between the three pathological tissue types;
2. Investigate a candidate mechanism mediating the tissue stiffening/extracellular matrix changes common across the three diseases;
3. Help to establish clinical cardiovascular features of high blood pressure in fibroid & keloid patients.
Techniques and Skills:
Histology/microscopy, cell culture/advanced in-vitro modelling, -omic analyses/bioinformatics, MRI analysis, patient data analysis
Yearly objectives:
Rotation: use histological and bioinformatic approaches to identify common histological, genetic, transcriptional, and/or proteomic features; in vitro modelling of the extracellular matrix representative of three tissues of interest; witness/understand gadolinium-enhanced cardiac MR scans; observe/gain competence in vascular measures in the clinical labs
Year1: complete hypothesis-generating rotation objectives; establish necessary tissue/cell collections; help recruiting Af/AfC women with imminent fibroid or keloid surgery +/- hypertension for cardiac/vascular health assessment;
Years 2&3: pursue mechanistic hypotheses generated in rotation/Year1 with lab-based strategies; complete/analyse/disseminate clinical data.
