Olga Cherepanova Laboratory

Research

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.   

Selected Publications

View publications for Olga Cherepanova, PhD
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HIGHLIGHTED PUBLICATIONS

1. Newman AAC, Baylis RA, Hess DL, Griffith SD, Shankman LS, Cherepanova OA, Owens GK. Irradiation abolishes smooth muscle cell investment into vascular lesions in specific vascular beds. JCI Insight, 2018, accepted for publication.
2. Murgai M, JuW, EasonW, KlineJ, Beury D, Kaczanowska S, MiettinenM, KruhlakM, LeiH, ShernJF, CherepanovaOA, OwensGK, KaplanRN. KLF4-dependent perivascular plasticity mediates pre-metastatic niche formation and metastasis. Nature Medicine, 2017, 23, 1176-1190
3. Durgin B, Cherepanova OA, Gomez D, Karaoli T, Alencar GF, Butcher J, Zhou Y-Q, Bendeck M, Isakson B, Owens GK, Connelly JJ. Smooth muscle cell-specific deletion of Col15a1 unexpectedly leads to impaired development of advanced atherosclerotic lesions. AJP Heart, 2017 (Published on-line -  DOI: 10.1152/ajpheart.00029.2017)
4. Cherepanova OA, GomezD, Shankman LS, Swiatlowska P, WilliamsJ, Sarmento OF, Alencar FG, Bevard MH, Greene ES, Murgai M, Turner SD, Geng Y-J, Bekiranov S, Connelly JJ, Tomilin A, OwensGK. Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective. Nature Medicine, 2016, 22, 657-665.
5. Shankman LS, Gomez D, Cherepanova OA, Salmon M, Alencar FG, Haskins RH, Swiatlowska P, Newman AAC, Greene ES, Straub AC, Isakson B, Randolph GJ, Owens GK. KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. Nature Medicine 2015, 21, 628-637.
6. Murgai M, Tomas J., Cherepanova O.A., Pathak V, Rekosh D, Owens GK. Infection of tumor cells with Xenotrophic MLVs promotes the formation of immature blood vessels. J Retrovirology, 2013,10: 34.
7. Connelly J.J., Cherepanova O.A., Doss J.F., Karaoli T., Lillard T.,  Markunas C., Nelson S., Crosslin D.R., Wang T., Ellis P.D., Langford C.F., Haynes T., Seo D., Goldschmidt-Clermont P.J., Shah S.H., Kraus W., , Hauser E.R.,  Gregory S.G. Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis. Hum Mol Gen, 2013,22(25): 5107-20.
8. Cherepanova O.A., Pidkovka N.A., Sarmento O.F., Yoshida T., Gan Q., Adiguzel E., Bendeck M.P., Berliner J., Leitinger N., Owens G.K. Oxidized Phospholipids Induce Type VIII Collagen Expression and Vascular Smooth Muscle Cell Migration. Circ Res, 2009, 104: 609-618.
9. Pidkovka, N.A., Cherepanova O.A., Yoshida T., Alexander M.R., Deaton R.A., Tomas J.A., Leitinger N., Owens G.K. Oxidized Phospholipids Induce Phenotypic Switching of Vascular Smooth Muscle Cells In Vivo and In Vitro. Circ Res, 2007, 101: 792-801.