Delphine Gomez, PhD

Research Interests

The Gomez lab is focused on studying the functional role of epigenetic and transcriptional mechanisms in controlling key properties of vascular smooth muscle cells (SMC) including cell differentiation, lineage memory and plasticity in the context of major cardiovascular diseases including atherosclerosis.

The ability of blood vessels to undergo repair and adaptive remodeling is an essential property of higher organisms. Failure of adequate vascular remodeling contributes to a number of diseases including heart failure and diabetic complications. SMC reversible dedifferentiation, characterized by a temporary downregulation of the SMC marker genes including smooth muscle alpha actin (Acta2) and smooth muscle myosin heavy chain (Myh11) is a key process occurring vascular injury-repair that is tightly regulated by transcriptional mechanisms. SMC acquire a unique epigenetic signature during development from multipotential embryonic cells. Following treatment with the mitogen Platelet Derived Growth Factor-BB, cultured SMC down-regulate expression of SMC marker genes whereas their epigenetic signature persists, suggesting that it may serve as a lineage memory mechanism and be required for SMC

re-differentiation. To directly assess the functional role of the SMC-specific epigenetic programming, the Gomez lab develops novel tools to perform gene-specific epigenetic editing in vitro and in vivo. We utilize these tools in vitro and in vivo using smooth muscle cell lineage tracing 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 atherosclerosis.

 

Selected Publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. Gomez D, Kessler K, Michel JB, Vranckx R. Modifications of Chromatin dynamics control the TGF-?1/Smad2 perturbation in aneurysmal Vascular Smooth Muscle Cells. Circulation Research. 2013; 113: 881-890. doi: 10.1161/CIRCRESAHA.113.301989.
  6. 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.