Rupa Sridharan, PhD

Portrait of Rupa Sridharan, PhD
Assistant Professor
Cell and Regenerative Biology
2118 WID
33 N Orchard St
Madison, WI 53703
(608) 316-4422
Focus Groups: 
Signal Transduction
PhD, University of California, Los Angeles
Research Summary: 
Stem Cell Biology, Epigenetics of cell fate change, Induced Pluripotent Stem cells.
Research Detail: 

Embryonic stem (ES) cells have the ability to divide indefinitely and to differentiate into any tissue under the correct set of chemical stimuli. Transcription factor- mediated reprogramming, initially demonstrated in mouse somatic cells, is the process by which the overexpression of a few transcription factors, usually, Oct4, Sox2, c-Myc and Klf4 converts differentiated cells into induced pluripotent stem (iPS) cells. Multiple molecular and functional studies have shown that iPS cells are highly similar to ES cells. Human somatic cells can also be reprogrammed, providing iPS cells both as tools for translational research such as for in vitro drug screens and for cell replacement therapy. Only about 1 % of cells complete the reprogramming process suggesting that multiple barriers have to be overcome for this dramatic change in cell fate to occur. Research in the lab will be focused on understanding the epigenetic roadblocks to the reprogramming process to illuminate both the mechanisms that control pluripotency and the stability of the differentiated state.

Specifically, we want to answer the following questions:

  1. How do the reprogramming factors activate pluripotency loci?
  2. What controls the global chromatin structure during reprogramming?
  3. Are there common principles in the reversion of differentiation that can be applied to switching the lineage between two differentiated cell types?

Insights from these basic research studies may enable the rational development of more efficient methods of reprogramming somatic cells for use in therapeutic settings.

Selected Publications: 
Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance.Zaidan NZ, Walker KJ, Brown JE, Schaffer LV, Scalf M, Shortreed MR,Iyer G, Smith LM, Sridharan R.Stem Cell Reports. 2018 Feb 13;10(2):627-641. doi: 10.1016/j.stemcr.2017.12.016.PMID: 29358085
Primary Cilium-Mediated Retinal Pigment Epithelium Maturation Is Disrupted in Ciliopathy Patient Cells.May-Simera HL, Wan Q, Jha BS, Hartford J, Khristov V, Dejene R, Chang J, Patnaik S, Lu Q, Banerjee P, Silver J, Insinna-Kettenhofen C, Patel D, Lotfi M, Malicdan M, Hotaling N, Maminishkis A, Sridharan R, Brooks B, Miyagishima K, Gunay-Aygun M, Pal R, Westlake C, Miller S, Sharma R, Bharti K.Cell Rep. 2018 Jan 2;22(1):189-205. doi: 10.1016/j.celrep.2017.12.038.PMID: 29298421
Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes.Roy S, Sridharan R.Genome Res. 2017 Jul;27(7):1250-1262. doi: 10.1101/gr.215004.116. Epub 2017 Apr 19.PMID: 28424352
Alternative Routes to Induced Pluripotent Stem Cells Revealed by Reprogramming of the Neural Lineage.Jackson SA, Olufs ZP, Tran KA, Zaidan NZ, Sridharan R.Stem Cell Reports. 2016 Mar 8;6(3):302-11. doi: 10.1016/j.stemcr.2016.01.009. Epub2016 Feb 18.PMID: 26905202
A predictive modeling approach for cell line-specific long-range regulatory interactions.Roy S, Siahpirani AF, Chasman D, Knaack S, Ay F, Stewart R, Wilson M, Sridharan R.Nucleic Acids Res. 2016 Feb 29;44(4):1977-8. doi: 10.1093/nar/gkv1181. Epub 2015 Nov 5. No abstract available.PMID: 26546512
A predictive modeling approach for cell line-specific long-range regulatory interactions.Roy S, Siahpirani AF, Chasman D, Knaack S, Ay F, Stewart R, Wilson M, Sridharan R.Nucleic Acids Res. 2015 Oct 15;43(18):8694-712. doi: 10.1093/nar/gkv865. Epub 2015 Sep 3. Erratum in: Nucleic AcidsRes. 2016 Feb 29;44(4):1977-8.PMID: 26338778
Collaborative rewiring of the pluripotency network by chromatin and signalling modulating pathways.Tran KA, Jackson SA, Olufs ZP, Zaidan NZ, Leng N, Kendziorski C, Roy S, Sridharan R.Nat Commun. 2015 Feb 4;6:6188. doi: 10.1038/ncomms7188.PMID: 25650115
Initial characterization of histone H3 serine 10 O-acetylation.Britton LM, Newhart A, Bhanu NV, Sridharan R, Gonzales-Cope M, Plath K, Janicki SM, Garcia BA.Epigenetics. 2013 Oct;8(10):1101-13. doi: 10.4161/epi.26025. Epub 2013 Aug 15.PMID: 23949383
Proteomic and genomic approaches reveal critical functions of H3K9 methylationand heterochromatin protein-1γ inreprogramming to pluripotency.Sridharan R, Gonzales-Cope M, Chronis C, Bonora G, McKee R, Huang C, Patel S, Lopez D, Mishra N, Pellegrini M, Carey M, Garcia BA, Plath K.Nat Cell Biol. 2013 Jul;15(7):872-82. doi: 10.1038/ncb2768. Epub 2013 Jun 9.PMID: 23748610
The nexus of Tet1 and the pluripotency network.Jackson SA, Sridharan R.Cell Stem Cell. 2013 Apr 4;12(4):387-8. doi: 10.1016/j.stem.2013.03.007.PMID: 23561438