Years at WID2012 - present
- B.S., St. Xavier’s College, Mumbai, India
- M.S., University of Baroda, India
- Ph.D., University of California, Los Angeles
- Postdoctoral Research, Eli and Edythe Broad Stem Cell Institute, UCLA
The main scientific focus of the lab is in defining how the epigenome controls cell fate.During the development of a multicellular organism a single cell can give rise to an entire organism made of a multitude of cells of specialized function. Such functional specification is determined both by the levels of expression of transcription factors and the receptivity of the chromatin state of the target genes to the binding of such factors. Once cell identity is established, epigenetic modifications, including those on histones and DNA, can ensure that it is stably maintained through cell divisions. Cell fate can be altered by the overexpression of proteins from other cell types. One of the most dramatic examples of such cell fate conversion is the reprogramming of unipotent somatic cells to induced pluripotent stem cells (iPSCs). iPSCs can self renew indefinitely and differentiate into all other cell types similar to embryonic stem cells (ESCs). iPSCs bypass the ethical and practical constraints of using ESCs for regenerative therapy.
Our lab is focused on investigating how cell identity is established from a pluripotent state and how it can be disrupted to generate a new cell fate. For this purpose we use genome wide techniques to query the epigenome and transcriptome at the population and single cell level. Ultimately we are interested in applying the information from the mechanism of generating iPSCs to make them better suited for translational applications.
- Zaidan NZ, Walker KJ, Brown JE, Schaffer LV, Scalf M, Shortreed MR, Iyer G, Smith LM, Sridharan R.Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance.Stem Cell Reports.2018 Feb 13;10(2):627-641. doi: 10.1016/j.stemcr.2017.12.016. PMID: 29358085
- Buxton KE, Kennedy-Darling J, Shortreed MR, Zaidan NZ, Olivier M, Scalf M, Sridharan R, Smith LM. Elucidating Protein-DNA Interactions in Human Alphoid Chromatin via Hybridization Capture and Mass Spectrometry.J Proteome Res. 2017 Sep 1;16(9):3433-3442. doi: 10.1021/acs.jproteome.7b00448. Epub 2017 Aug 4. PMID: 28704058
- Roy S, Sridharan R. Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes. Genome Res. 2017 Jul;27(7):1250-1262.
- Jackson SA, Olufs ZP, Tran KA, Zaidan NZ, Sridharan R. (2016) Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage. Stem Cell Reports. 6:302-11.
- Roy S, Siahpirani AF, Chasman D, Knaack S, Ay F, Stewart R, Wilson M, Sridharan R. (2016) A predictive modeling approach for cell line-specific long-range regulatory interactions. Nucleic Acids Res. 44:1977-8.
- Tran, K.A., Jackson, S.A., Olufs, Z.P.G., Zaidan, N.Z., Leng, N., Kendziorski, C., Roy, S., and Sridharan, R. (2015) Collaborative rewiring of the pluripotency network by chromatin and signaling modulating pathways. Nat Commun. 6:6188. doi: 10.1038/ncomms7188.
- Jackson, S.A. and Sridharan, R. (2013) The nexus of Tet1 and the pluripotency network. Cell Stem Cell 12, 387-88
- Jackson, S.A. and Sridharan, R. (2013) Peering into the black box of reprogramming to the pluripotent state. Curr Pathobiol Rep, 1,129-136
- Sridharan, R., Gonzales-Cope, M., Chronis, C.,Bonora, G., McKee, R., Patel,S., Lopez,D., Mishra, N., Pellegrini, M., Carey, M., Garcia, B.A. and Plath, K. (2013) Proteomic and genomic approaches reveal critical functions of H3K9 methylation and Heterochromatin Protein-1g in reprogramming to pluripotency. Nat Cell Bio doi10.1038/ncb2768
- Sridharan R *., Tchieu J *., Mason M.J. *. , Yachechko R., Kuoy E., Horvath S., Zhou Q. and Plath K. (2009). Role of the murine reprogramming factors in the induction of pluripotency. * authors contributed equally to this work. Cell 136 (2), 364-77
- Maherali, N.*, Sridharan, R.*, Xie, W., Utikal, J., Eminli, S., Arnold, K., Stadtfeld, M., Yachechko, R., Tchieu. J., Jaenisch, R., Plath, K.#, and Hochedlinger, K.# (2007). Global epigenetic remodeling in directly reprogrammed fibroblasts. * both authors contributed equally to this work; # co-corresponding authors. Cell Stem Cell 1, 55-70