Cardiovascular Genomics (Kaikkonen lab)

Coronary artery disease (CAD) is the leading cause of death in the Western world. To improve CAD prevention, diagnosis and treatment, we need to gain better understanding of the gene regulatory and genetic factors that promote its progression. Especially, we are still far from understanding how different cell types such as endothelial cells (ECs), macrophages (Mɸs) and smooth muscle cells (SMCs) in the developing lesion contribute to the disease. In addition, accumulation of lipids and chronic inflammation are hallmarks of CAD and there is a clear consensus that liver, through regulation of cholesterol homeostasis, and dysfunctional adipose tissue may directly influence the function of cells of the vessel wall.

Our research team aims to decipher the cell-type specific contribution of ECs, Mɸs and SMCs in CAD progression by characterizing the gene regulatory processes that take place at the level of chromatin organization, transcription, post-transcription and translation in response to proartherogenic stimuli. The data gained here is used to identify gene regulatory mechanisms responsible for the altered expression of atherosclerosis risk genes and to construct a model of gene regulation during CAD development. Secondly, we aim to bring the functional characterization of genetic variants associated with CAD to date by identifying and interpreting the role of enhancer variants across all five disease relevant cell types. As majority of CAD-variants are located within these noncoding regulatory regions, establishing causal relationships between enhancer activity and coding gene expression can be used to translate genetic signals into biological mechanisms that could further lead to prognostic, diagnostic and therapeutic advances. Altogether, this work holds promise in obtaining a more complete picture of gene regulatory programs and causal events driving CAD development.

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