Close
PhD Project Title: Discovery and validation of therapeutic targets for heart failure using expression and protein quantitative trait loci in Mendelian randomisation framework
Supervisors: Dr Tom Lumbers
Lay summary:
Heart failure is a growing problem for which understanding of causal human biology is limited. Pre-clinical models are poorly predictive of late-phase efficacy and there are no validated intermediate outcomes to use as surrogate outcomes in clinical trials. A number of genes are implicated in heart failure aetiology from non-human models, human observational biomarker, and genome-wide association studies (GWAS); however causal validation of these markers in trials has remained elusive. Mendelian randomisation analysis using genetic variants altering the abundance or function of gene transcripts or their cognate protein as instruments can be used to test for a causal role of a gene in a disease outcome, in this case heart failure and related intermediate phenotypes. GWAS of multiplexed aptamer- and affinity-based assays (Somascan, OLink) of serum proteins have discovered numerous cis- and trans- protein quantitative trait loci (pQTLs) for a significant proportion of the serum proteome. Similarly, GWAS of gene expression has identified multiple expression quantitative trait loci (eQTLs) associated with gene expression in different human tissues. The aim of this project is to investigate the causal role of genes in heart failure aetiology by Mendelian randomisation using genetic instruments derived from serum protein and expression quantitative trait loci.
My Background
I am a BHF 4-year Cardiovascular Biomedicine PhD student of 2018/2019 cohort. Formerly, I was a general practitioner with a few years experience of clinical work in Indonesia. I came to the UK in 2016 to undertake the MSc course in Health and Biomedical Data Science and then worked as a research assistant with the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) consortium working group, both at UCL. I have a broad interest in the use of large-scale datasets (e.g. biobank, omics, electronic health record) in modern clinical and biomedical research. Cardiovascular disease is of my particular interest as there is an emerging challenge of a global epidemiology change (e.g. increasing prevalence of heart failure due to better acute cardiovascular event management), but there is also a big opportunity to utilise the ever-growing resources and knowledge base to accelerate cardiovascular research. My current research interest is around the area of genetic & molecular epidemiology. More generally, I am also interested in human & population genetics, genomic medicine, data science, and bioinformatics.
Qualifications
• MD (general practice) – Diponegoro University, Indonesia (2014)
• MSc in Health & Biomedical Data Science – UCL, UK (2017)
Awards
• UCL Faculty of Population Health Dean’s list of outstanding students 2016/2017
• Best Poster Presentation in Alzheimer’s Disease International Asia Pacific Region Conference 2017
Contact details
• Email: albert.henry.16@ucl.ac.uk
• Twitter: maha_albert
• LinkedIn: https://www.linkedin.com/in/albhenry/