Assistant Professor of Cell and Regenerative Biology
Epigenetics of cell fate change
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 percent 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 focuses 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:
- How do the reprogramming factors activate pluripotency loci?
- What controls the global chromatin structure during reprogramming?
- 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.
Roy, S.* and Sridharan, R.*, Chromatin module inference on cellular trajectories identifies key transition points and poised epigenetic states in diverse developmental processes. Genome Research (in press, available online Apr 17, 2017).*co-corresponding authors
Jackson, S.A. *, Olufs, Z.P.G. *, Tran, K.A., Zaidan, N.Z., and Sridharan, R. (2015) Alternative routes to induced pluripotent stem cells revealed by reprogramming of neural lineage. Stem Cell Reports (in press, available online Feb 18 2016). * co-first authors.
Current lab members
The Sridharan Lab is seeking a strong candidate for the position of postdoctoral fellow. Please contact Rupa Sridharan.