Danish Saleheen, MBBS, PhD
Dr. Saleheen’s research program is dedicated towards understanding genetic, blood-based and lifestyle factors that cause cardiovascular disorders. Some of the major ongoing projects are:
1. Dr. Saleheen is leading a number of research projects in Pakistan. His research team has already enrolled more than 65,000 participants on whom extensive lifestyle information and biological samples have been collected. This biological resource includes approximately 21,000 participants with heart attacks, 6,000 patients with imaging confirmed stroke, 10,000 patients with type-2 diabetes, 3000 patients with heart failure and 28,000 healthy participants. This research program is being rapidly expanded to include 200,000 participants. Some of the other phenotypes that will be captured include chronic kidney disease and non-alocholic fatty liver disease. A number of state-of-the art measurements have alredy been conducted in a large majority of these participants, including evaluation of millions of genetic markers and more than 200 blood-based factors.
2. Call back studies in Human Knockouts. Dr. Saleheen's group is particularly leveraging the high levels of consanguinity in Pakistan; for instance close to 40% of the participants in the bioresource that he has established are born of first cousin marriages. Through WES studies in this highly inbred population, Dr. Saleheen's group has identified a number of null homozygotes (i.e., human knockouts). These human knockouts are being systematically evaluated through deep phenotyping studies. For instance, Dr. Saleheen's group has identified the world's first humans who are completely deficient of APOC3.
3. Causal evaluation of emerging biological pathways . Dr. Saleheen's group is integrating evidence from large scale genetic studies, biomarker studies, and functional experiments to help assess causal nature of several emerging biological pathway. This aspect involves understanding the relationship of blood-based biomarkers with risk of cardiovascular diseases through traditional epidemiological approaches, such as Mendelian randomization studies. More recently, this research program has also expanded to conduct mechanistic studies in mice and human cells with a specific focus on CHD loci discovered through GWAS (e.g., R-01 on the CXCL12 CHD locus) and by conducting call-back studies.
4. Gene*Environment Interactions. Genetic predisposition to heart attacks and stroke may be modified by lifestyle factors. Dr. Saleheen's group is interested in identifying factors that influence these genes to cause disease. For instance, his group is interested to find genes that could make those who smoke more vulnerable to develop heart attacks compared to those who do not smoke.
Data download for “Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease”
Dataset (T2D discovery analyses) http://www.med.upenn.edu/ccebfiles//t2d_meta_cleaned.zip
Dataset (T2D and CHD bivariate scan) http://www.med.upenn.edu/ccebfiles/chd_t2d_af_gwas12_cleaned_combined_1000gRefAlt_added_pvalRescaled_varSetID_added.zip
Cardiovascular epidemiology, genetic epidemiology, molecular epidemiology