Location: Cleveland Clinic Main Campus
Our lab is interested in molecular and cellular mechanisms responsible for smooth muscle cell (SMC) and endothelial cells (EC) phenotypic transitions. We use a combination of preclinical and cell culture models in combination with the bioinformatics analyses such as bulk and single cells RNA-sequencing to better understand these transitions, with the goal to develop novel therapeutic interventions for stabilizing atherosclerotic plaques in order to reduce the risk of plaque rupture with possible myocardial infarction or stroke.
The long-term scientific interest of our laboratory is in elucidating molecular mechanisms responsible for the phenotypic transition of vascular cells, including smooth muscle cells (SMCs), macrophages and endothelial cells (ECs) during atherosclerosis development and after vascular injury, as well as mechanisms responsible for migration, proliferation, and extracellular matrix synthesis by phenotypically modulated vascular cells. We use SMC- and EC-lineage tracing mouse models that allow us to trace phenotypically modulated cells in pathological conditions.
Recently, we found that the embryonic stem cell factor OCT4 plays an athero-protective role in SMCs by regulating SMC phenotypic transition, including migration and SMC investment into fibrous cap (Cherepanova et al., Nature Med, 2016). There is a growing interest in the pluripotency factors (OCT4, KLF4, c-MYC and SOX2) required for the reprogramming of somatic cells into iPS cells, a discovery that won Dr. Yamanaka the Nobel Prize in 2012. In spite of multiple papers reporting that the pluripotency isoform of OCT4 might be expressed in somatic cells, our recent study in SMCs is the first to provide direct evidence that OCT4 plays an important functional role in adult somatic cells.
Project 1: The overall goal of our current project in the lab is to test if activation of the pluripotency factor OCT4 within ECs plays a key functional role during atherosclerosis development through regulation of EC activation and dysfunction, including EC-monocyte adhesion, Endo-MT, and EC migration. We generated EC-lineage tracing EC-specific OCT4 knockout Apoe knockout mice to test if genetic inactivation of OCT4 in EC is athero-promoting.
Project 2: The lethal consequences of atherosclerosis, including myocardial infarction or stroke, occur well after our reproductive years. Therefore, the overall goal of our current project is to identify a baseline functional role for OCT4 in endothelial cells, as well as to test whether OCT4 plays a protective role in EC after acute vascular injury to enhance processes critical for injury repair.
View publications for Olga Cherepanova, PhD
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The paper outlined the cellular differences that could tie to sex-specific presentations of heart disease.