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Adults (18-65), Geriatrics (65+)
Adults (18-65), Geriatrics (65+)
Research Interests: We are interested in how genome organization shapes organogenesis.Keywords: Nuclear architecture, gene regulation, chromatin, epigenetics, 3D genome organization, heart development, stem cell biologyResearch Details: An overarching goal is to understand cell identity is established and maintained. We combine traditional molecular biology and genetic tools with innovative imaging and next-generation sequencing approaches to define how an embryonic stem cell progressively restrict their potential to give rise to various differentiated cell types in the body. We also routinely leverage classic models of stem cell biology to dissect the underpinnings of cell fate decisions. We have a focus on cardiac biology but routinely work outside it. It has become clear that the genome is folded and organized in a stereotypical manner in three- dimensional space. A major interest of the laboratory is deciphering how the organization of the genome in 3D space regulates genes and cell fate decisions. We are defining how the nuclear lamina, a network of proteins on the inner side of the nuclear membrane, interacts with chromatin to drive gene regulation and shape cell fate choices. Projects in the laboratory are geared towards defining the rules that govern nuclear lamina-chromatin interactions. We are also studying how mutations in LMNA and related proteins impact nuclear architecture and translate into cardiac dysfunction in patients.Lab Personnel:Rajan JainRicardo Llinares SaldanaNicholas RizerParisha ShahQiaohong Wang
Poleshko A*, Shah PP*, Gupta M*, Babu A, Morley MP, Manderfield LJ, Ifkovits JL, Calderon D, Aghajanian H, Sierra-Pagán JE, Sun Z, Wang Q, Li L, Dubois NC, Morrisey EE, Lazar MA, Smith CL, Epstein JA*, Jain R*: Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction Cell 171 (3): 573-587 e14,2017.
Aghajanian H, Cho YK, Rizer NW, Wang Q, Li L, Degenhardt K, Jain R: Pdgfralpha functions in endothelial-derived cells to regulate neural crest cells and the development of the great arteries Dis Model Mech 10 (9): 1101-1108,2017.
Ramjee V, Li D, Manderfield LJ, Liu F, Engleka KA, Aghajanian H, Rodell CB, Lu W, Ho V, Wang T, Li L, Singh A, Cibi DM, Burdick JA, Singh MK*, Jain R*, Epstein JA*: Epicardial YAP/TAZ orchestrate an immunosuppressive response following myocardial infarction J Clin Invest 127 (3): 899-911,2017.
Jain R*, Li D*, Gupta M, Manderfield LJ, Ifkovits JL, Wang Q, Liu F, Liu Y, Poleshko A, Padmanabhan A, Raum JC, Li L, Morrisey EE, Lu MM, Won KJ, Epstein JA: Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts Science 348 (6242): aaa6071,2015.
Loh KM, Chen A, Koh PW, Deng TZ, Sinha R, Tsai JM, Barkal AA, Shen KY, Jain R, Morganti RM, Shyh-Chang N, Fernhoff NB, George BM, Wernig G, Salomon REA, Chen Z, Vogel H, Epstein JA, Kundaje A, Talbot WS, Beachy PA, Ang LT, Weissman IL: Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types Cell 166 (2): 451-467,2016.
Kook H, Seo SB, Jain R: EZ Switch From EZH2 to EZH1: Histone Methylation Opens a Window of Cardiac Regeneration Circ Res 121 (2): 91-94,2017.
Jain R*, Barkauskas CE*, Takeda N, Bowie EJ, Aghajanian H, Wang Q, Padmanabhan A, Manderfield LJ, Gupta M, Li D, Li L, Trivedi CM, Hogan BL, Epstein JA: Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung Nat Commun 6 : 6727,2015.
Takeda N*, Jain R*, Leboeuf MR, Padmanabhan A, Wang Q, Li L, Lu MM, Millar SE, Epstein JA: Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells Development 140 (8): 1655-64,2013.
Takeda N*, Jain R, LeBoeuf MR, Wang Q, Lu MM, Epstein JA.: Interconversion between intestinal stem cell populations in distinct niches Science 334 (6061): 1420-4,2011.
Jain R, Engleka KA, Rentschler SL, Manderfield LJ, Li L, Yuan L, Epstein JA: Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves J Clin Invest 121 (1): 422-30,2011.
High FA*, Jain R*, Stoller JZ, Antonucci NB, Lu MM, Loomes KM, Kaestner KH, Pear WS, Epstein JA: Murine Jagged1/Notch signaling in the second heart field orchestrates Fgf8 expression and tissue-tissue interactions during outflow tract development J Clin Invest 119 (7): 1986-96,2009.
Ladurner AG, Inouye C, Jain R, Tjian R: Bromodomains mediate an acetyl-histone encoded antisilencing function at heterochromatin boundaries Mol Cell 11 (2): 365-76,2003.
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