The Sridharan Laboratory
Faculty > Rupa Sridharan
Rupa Sridharan
Assistant Professor, Cell and Regenerative Biology
rsridharan@discovery.wisc.edu
Sridharan Laboratory Home Page
Aligned Research Focus
Basic stem cell science
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.
Selected References
Sridharan, R. and Plath, K. (2011) Small RNAs loom large during reprogramming. Cell Stem Cell 8, 599-601.
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.
Sridharan, R. and Plath, K. (2008) Illuminating the black box of reprogramming. Cell Stem Cell 2, 295-297.
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.
Xie, W., Song, C., Sperling, A., Xu, F., Sridharan, R., Conway, A., Plath, K., Clark, A.T. and Grunstein, M. (2009) Histone H3 K56 acetylation marks canonical histone genes and the core transcriptional network for pluripotency in human embryonic stem cells. Mol Cell 33(4), 417-27.