Education & Training
- BS- Biology & Physiology, University Paris Diderot, 2005
- MS- Cell Biology, Physiology and Pathology, University Paris Diderot, 2006
- PhD- Biology and Physiology of the Vascular system, University Paris Diderot, 2010
Research Interest Summary
The Gomez lab studies the functional role of epigenetic and transcriptional mechanisms in controlling fundamental properties of vascular smooth muscle cells. Using a combinatorial approach of epigenomic (Cut & Cut&Tag, ATACseq), transcriptomic (RNAseq), and functional assays, we aim to characterize the causal relationship between chromatin states or non-coding RNA signatures establishment and maintenance of vascular cell lineage identity and functions. Identifying and understanding such mechanisms is particularly relevant considering the inherent phenotypic plasticity of vascular smooth muscle cells and their ability to react to changes in their environment dynamically.
Vascular smooth muscle cells are highly specialized contractile cells responsible for maintaining vascular integrity and control of the vascular tone. However, during an adaptive or maladaptive response to environmental cues, smooth muscle cells can profoundly alter their contractile phenotype and undergo a dedifferentiation process called “phenotypic switching” characterized by the loss of expression of the smooth muscle lineage gene repertoire and the concomitant enhancement in their ability to proliferate, migrate or produce extracellular matrix. In some instances, including adaptive vascular remodeling, smooth muscle cells can re-differentiate into contractile cells after transient phenotypic switching indicating persistence in lineage identity.
Our lab is particularly interested in the epigenetic mechanisms (histone modifications, DNA methylation) guaranteeing the retention of smooth muscle cell lineage identity and their functional relevance during vascular development, remodeling, and diseases. We develop novel tools to perform gene-specific epigenetic editing in vitro and in vivo. We utilize these tools in smooth muscle cell fate mapping mice to determine the role of lineage-specific epigenetic programming in controlling cell identity, lineage memory, differentiation, and plasticity during blood vessel formation, acute vascular injury-repair processes, and chronic vascular diseases such as aortic aneurysm, hypertension, atherosclerosis, and peripheral artery disease.
Liu M, Espinosa-Diez C, Mahan S, Du M, Nguyen AT, Hahn S, Straub AC, Martin KA, Owens GK, Gomez D. H3K4 di-methylation controls smooth muscle cell epigenetic memory, lineage identity and vascular homeostasis. SSRN 3708519 [Preprint]. October 22, 2020. Available from: http://dx.doi.org/10.2139/ssrn.3708519.
Liu M, Gomez D. Smooth Muscle Cell phenotypic diversity: At the crossroads of lineage tracing and single-cell transcriptomics. Arterioscler Thromb Vasc Biol. 2019 Jul 25:ATVBAHA119312131. doi: 10.1161/ATVBAHA.119.312131.
Mahan S, Liu M, Baylis RA, Gomez D. Quantitative analysis of cellular composition in advanced atherosclerotic lesions of smooth muscle cell lineage tracing mice. J Vis Exp. (144), e59139, doi:10.3791/59139 (2019).
Gomez D, Baylis RA, Durgin BG, Newman AAC, Alencar GF, Mahan S, St. Hilaire C, Muller W, Waisman A, Francis SE, Pinteaux E, Randolph GJ, Gram H, Owens GK. Interleukin-1β promotes atheroprotective effects of advanced atherosclerotic lesions in mice. Nature Medicine. 2018 Sep;24(9):1418-1429. doi: 10.1038/s41591-018-0124-5. Epub 2018 Jul 23.
Cherepanova OA, Gomez D, Shankman LS, Swiatlowska P, Williams J, Sarmento OF, Alencar GF, Bevard MH, Greene ES, Murgai M, Turner SD, Geng YJ, Connelly JJ, Bekiranov S, Tomilin A, Owens GK. The stem cell pluripotency factor Oct4 induces atheroprotective changes in SMC phenotype. Nature Medicine. 2016 Jun;22(6):657-65. doi: 10.1038/nm.4109.
Gomez D, Swiatlowska P, Owens GK. Epigenetic control of SMC identity and lineage memory. Arterioscler Thromb Vasc Biol. 2015 Dec;35(12):2508-16. doi: 10.1161/ATVBAHA.115.305044.
Shankman L, Gomez D, Cherepanova O, Salmon M, Alencar GF, Haskins RM, Swiatlowska P, Newman AAC, Greene ES, Straub AC, Isakson B, Randolph GJ, Owens GK. KLF4-dependent phenotypic modulation of smooth muscle cells has key role in atherosclerotic plaque pathogenesis. Nature Medicine. 2015 Jun;21(6):628-37. doi: 10.1038/nm.3866.
Gomez D, Shankman S, Nguyen AT, Owens GK. Detection of Histone Modifications of Specific Gene Loci in Single Cells in Histological Sections. Nature Methods. 2013; 10:171–177. doi: 10.1038/nmeth.2332.
Gomez D, Kessler K, Michel JB, Vranckx R. Modifications of Chromatin dynamics control the TGF-β1/Smad2 perturbation in aneurysmal Vascular Smooth Muscle Cells. Circulation Research. 2013; 113: 881-890. doi: 10.1161/CIRCRESAHA.113.301989.
Gomez D, Coyet A, Ollivier V, Jeunemaitre X, Jondeau G, Michel JB, Vranckx R. Epigenetic control of vascular smooth muscle cells in Marfan and non-Marfan thoracic aortic aneurysms. Cardiovascular Research. 2011 Feb 1;89(2):446-56. doi: 10.1093/cvr/cvq291.