Dr Nicholas Blackburn - University of Texas Rio Grande Valley

Dr Nicholas Blackburn - University of Texas Rio Grande Valley

Seminar Room 2
Start Time: 
Mon, 17/12/2018 - 1:00pm
End Time: 
Mon, 17/12/2018 - 2:00pm

​Untangling the plasma lipidome in cardiovascular disease

​Special seminar hosted by Professor Melanie Bahlo

Cardiovascular disease (CVD) is complex group of disorders which together are the leading cause of death worldwide. The genetic risk underlying CVD is well established however the basis of this risk is unknown. Understanding this risk and identifying drug targets for preventative treatment is of significant clinical interest. Using a longitudinal family-based study of Mexican Americans, the San Antonio Family Heart Study, we have profiled the plasma lipidome in over 1000 individuals to search for new quantitative endophenotypes related to CVD liability. This lipidome profiling goes far deeper than the classical lipid measures of HDL-C, LDL-C and triglycerides and provides quantitative identification of individual lipid components. We have hypothesized that these lipid components are more closely related to the direct biology of genes and thus may facilitate discovery of genes causally involved in CVD risk.

With whole genome sequence data from this entire cohort we have begun to draw direct connections between population rare genetic variants predicted to affect gene function, and levels of individual lipid species related to CVD. A major strength of the family based design of this study is that Mendelian transmission of population rare variants means that there are sufficient numbers of carriers within this cohort for single variant analysis. One such example is a loss-of-function 5-basepair coding deletion, rs569107562, in ANGPTL3 (Angiopoietin-like 3) a known CVD target. Previously identified by others as causing familial hypolipidemia in homozygous carriers, we identified 22 heterozygotes with this variant in a single Mexican American family. In publicly available population frequency databases this variant is extremely rare and occurs in only 63/116,776 of individuals (<0.03%).  ANGPTL3 is a liver protein that has roles in lipid metabolism through the inhibition of lipoprotein lipase and endothelial lipase. Loss-of-function mutations in ANGPTL3 are known to be protective against CVD through their association with decreased plasma levels of triglycerides, LDL-C and HDL-C. Using our lipidome profiles we have been able to explore beyond the known effects of ANGPTL3 on the classical lipid parameters and have identified novel associations with several phosphatidylinositol lipid species. Given the growing interest in ANGPTL3 as a CVD target this novel phosphatidylinositol relationship warrants further investigation.

Tasmanian born, Dr Nicholas Blackburn is a graduate of the University of Tasmania and Menzies Institute for Medical Research where he completed his PhD in 2015 on the genetic and genomic analysis of Tasmanian families with haematological malignancies. In early 2016 he moved to South Texas where he joined Dr John Blangero’s laboratory at the newly formed University of Texas Rio Grande Valley School of Medicine.

Dr Blackburn’s expertise span both the wet and dry laboratory, and covers most recent ‘omic technologies with a focus on DNA and RNA seq, and a special emphasis on the use of next-generation sequencing in large, complex pedigree structures, and quantitative phenotypes. His primary research centres around the analysis of WGS data from multigenerational pedigrees in the ongoing and longitudinal San Antonio Family Heart Study. Working closely with Dr Joanne Curran, Dr Blackburn leads the analysis of novel lipidomic datasets and quantitative phenotypes in Mexican American families with the goal of identifying new genetic factors related to cardiovascular disease risk. In the non-human field, through a community based wildlife organization Dr Blackburn has also initiated and leads a pilot study to identify the genetic drivers of a tumour-based disease, called fibropapilloma, that threatens endangered sea turtle populations locally and globally.