Assistant Professor of Medicine
Perelman School of Medicine
Location: Smilow TRC 9-102
Admin: Emily Romick
Our overarching goal is to understand how cells establish and maintain their identity. We are particularly interested in how cardiac cell types are specified, and the implications of this process for diseases, including congenital heart disease and congestive heart failure. 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 entire 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.
CELL IDENTITY | GENOME ORGANIZATION
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 dynamic spatial distribution of the genome in the nucleus underlies establishment and maintenance of cell fate and that decoding the rules that instruct nuclear lamina-chromatin interactions will inform how this is achieved. We are interested in:
- Discovery: Comprehensively defining peripheral chromatin domains across human lineages.
- Mechanism: Deciphering how spatial distribution of chromatin shapes cell fate.
- Disease: Determining how nuclear architecture drives laminopathy phenotypes.
We work across disciplines and collaborate with clinicians and scientists of all backgrounds to tackle our questions, using a combination of single-cell, next generation sequencing, live imaging, and proteomic approaches.
- Poleshko, A.*, Shah, P. P.*, Gupta, M.*, Babu, A., Morley, M. P., Manderfield, L. J., Ifkovits, J. L., Calderon, D., Aghajanian, H., Sierra-Pagan, J. E., Sun, Z., Wang, Q., Li, L., Dubois, N. C., Morrisey, E. E., Lazar, M. A., Smith, C. L., Epstein, J. A.**, Jain, R.**: Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction. Cell. 171(3): 573-587 e14, 2017.
- Aghajanian, H., Cho, Y. K., Rizer, N. W., 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. (Featured on cover)
- Jain, R., Li, D., Gupta, M., Manderfield, L.J., Ifkovits, J.L., Wang, Q., Liu, F., Liu, Y., Poleshko, A., Padmanabhan, A., Raum, J.C., Li, L., Lu, M.M., Won, K., Epstein, J.A. Integration of Bmp and Wnt signaling by Hopx specifies commitment of cardiomyoblasts. Science. 348(6242): aaa6071, Jun 2015. PMCID: PMC4806339. (Featured on cover; Commentary in Molecular Therapy)
- Jain, R., Barkauskas, C.E., Takeda, N., Wang, Q., Aghajanian, H., Manderfield, L.M., Gupta, M., Padmanabhan, A., Li, D.Q., Li, L., Trivedi, C.M., Hogan, B.L., Epstein, J.A. Plasticity of Hopx+ Type I alveolar cells to regenerate Type II cells in the lung. Nat Commun. 2015 Apr 13;6:6727.
- Takeda, N.*, Jain, R.*, LeBoeuf, M.R., Wang, Q., Lu, M.M., Epstein, J.A. Inter-conversion between intestinal stem cell populations in distinct niches. Science. 2011 Dec 9; 334(6061):1420-4. *Co-first author (Commentary in Cell Stem Cell)
- Jain, R., Engleka, K.A., Rentschler, S.L., Manderfield, L.J., Li, L., Yuan, L., Epstein, J.A. Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves. J Clin Invest. 2011 Jan 4; 121(1):422-30.