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 biology
Our overarching goal is to understand how cells establish and maintain their identity. We leverage classic models of stem cell biology and readily work across disciplines to dissect the underpinnings of how genome organization shapes cell identity and fate. We work on this because it is not well understood how gene programs are coordinately enacted, such as those that happen as a cell progressively restricts. In addition, the promise of cell-based regenerative therapies requires the efficient generation of cells and tissues. We hope our studies will help add to the foundation for these efforts. Some of our efforts on cardiac progenitor lineage restriction and thus we are interested in the implications of our work in understanding congenital heart disease and adult cardiac diseases.
The higher-order mechanisms that control cell fate are relatively poorly understood. It has become apparent that the genome is folded and organized in a stereotypical manner in three-dimensional space. We are interested in understanding how the organization of the genome in 3D space establishes and maintains cell identity. Our team focuses on the central hypothesis that proper genome folding and dynamic spatial organization of the genome in the nucleus underlies the establishment and maintenance of cellular identity. We believe that decoding the rules that instruct genome organization and lamina-chromatin interactions will inform how this is achieved.
Bailey Koch-Bojaland (Postdoctoral Fellow)
Zachary Gardner (CAMB/GE MD/PhD Student)
Ashley Karnay (CAMB/GE Graduate Student)
Wonho Kim (Postdoctoral Fellow)
Ricardo Linares-Saldana (CAMB/GE MD/PhD Student)
Garrett Santini (MTR Student, Penn Medical Student)
Parisha Shah (Senior Research Investigator)
Kaitlyn Shen (CAMB/GE MD/PhD Student)
Qiaohong Wang (Staff)
Rachel Yang (Sarnoff Cardiovascular Research Fellow)
Linares-Saldana R*, Kim W*, Bolar NA*, Zhang H, Koch-Bojalad BA, Yoon S, Shah PP, Karnay A, Park DS, Luppino JM, Nguyen SC, Padmanabhan A, Smith CL, Poleshko A, Wang Q, Li L, Srivastava D, Vahedi G, Eom GH, Blobel GA, Joyce EF, Jain R: BRD4 orchestrates genome folding to promote neural crest progenitor differentiation. Nature Genetics 53(10): 1480-1492, October 2021 Notes: Featured in News and Views, Nature Genetics, April 2022.
Shah PP*, Lv W*, Rhoades JH, Poleshko A, Abbey D, Caporizzo MA, Heffler JG, Sayed N, Thomas D, Linares-Saldana R, Wang Q, Stanton LJ, Bedi K, Morley MP, Cappola TP, Owens AT, Margulies KB, Frank DB, Wu JC, Rader DJ, Yang W, Prosser BL, Musunuru K**, Jain R**: Pathogenic LMNA variants disrupt cardiac lamina-chromatin interactions and de-repress alternative fate genes. Cell Stem Cell 28(5): 938-954, May 2021.
Mellis IA, Edelstein HI, Truitt R, Goyal Y, Beck LE, Symmons O, Dunagin MC, Linares Saldana RA, Shah PP, Pérez-Bermejo JA, Padmanabhan A, Yang W, Jain R*, Raj A*: Responsiveness to perturbations is a hallmark of transcription factors that maintain cell identity in vitro. Cell Systems 12(9): 885-899, September 2021 Notes: *co-corresponding author.
Alexanian M, Prztycki P, Micheletti R, Padmanabhan A, Ye L, Travers JG, Teran BG, Duan Q, Ranade SS, Felix F, Linares-Saldana RA, Huang Y, Andreoletti G, Yang J, Ivey K, Jain R, McKinsey TA, Rosenfeld MG, Gifford C, Pollard KS, Haldar SM, Srivastava D: A transcriptional switch governs fibroblast activation in heart disease. Nature 595(7867): 438-443, Jul 2021.
Padmanabhan A*, Alexanian M*, Linares-Saldana RA*, Gonzalez-Teran B, Andreoletti G, Huang Y, Connolly AJ, Kim W, Hsu A, Duan Q, Winchester S, Haldar SM, Jain R**, Srivastava D** : BRD4 Interacts with GATA4 to Govern Mitochondrial Homeostasis in Adult Cardiomyocytes. Circulation 142(24): 2338-2355, Dec 15 2020 Notes: **co-corresponding author.
Frank DB**, Penkala IJ, Zepp JA, Sivakumar A, Linares-Saldana R, Zacharias WJ, Stolz KG, Pankin J, Lu M, Wang Q, Babu A, Li L, Zhou S, Morley MP, Jain R**, Morrisey EE** : Early lineage specification defines alveolar epithelial ontogeny in murine lung Proceedings of the National Academy of Sciences 116(10): 4362-4371, February 2019 Notes: **co-corresponding author.
Aghajanian H, Kimura T, Rurik JG, Hancock AS, Leibowitz MS, Li L, Scholler J, Monslow J, Lo A, Han W, Wang T, Bedi K, Morley MP, Linares-Saldana RA, Bolar NA, McDaid K, Assenmacher C-A, Smith CL, Wirth D, June CH, Margulies KB, Jain R, Puré E, Albelda SM, Epstein JA: Targeting cardiac fibrosis with engineered T cells. Nature 573(7774): 430-433, September 2019.
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, Oct 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. Disease Models & Mechanisms 10(9): 1101-1108, Sept 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, Jun 2015.
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Last updated: 01/19/2023
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