University of Wisconsin–Madison
College of Agriculture and Life Sciences | School of Medicine and Public Health

Rupa Sridharan

Assistant Professor

rsridharan@discovery.wisc.edu

608-316-4422

Cell and Regenerative Biology
Epigenetics and Induced pluripotent stem cells

Address
2118 Wisconsin Institutes for Discovery
Education
Ph.D., University of California, Los Angeles (2006), Postdoctoral Research: Broad Stem Cell Institute, UCLA
Lab Website
http://www.crb.wisc.edu/faculty/sridharan.asp
Department
Cell and Regenerative Biology
Research Interests
Epigenetics and Induced pluripotent stem cells
Research Fields
Development, Gene Expression, Genomics & Proteomics, Human, mouse & rat

Research Description:
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.

Topics of interest include:

Transcription factor mediated reprogramming

Histone post-translational modification changes

Cell fate maintenance

Epigenetics


Representative Publications:
Search PubMed for more publications by Rupa Sridharan

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) Peering into the black box of reprogramming to the pluripotent state. Curr Pathobiol Rep, 1,129-136.

Jackson, S.A. and Sridharan, R. (2013) The nexus of Tet1 and the pluripotency network. Cell Stem Cell, 12, 387-88.

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-1γ in reprogramming to pluripotency. Nat. Cell. Bio. 15(7):872-82

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

Lowry, W. E., Richter, L .,Yachechko, R., Pyle, A. D., Tchieu, J., Sridharan, R., Clark, A. T. and Plath, K.(2008) Generation of human induced pluripotent cells from dermal fibroblasts. PNAS 105, 2883-2888