Samantha A. Morris, Ph.D.

Assistant Professor
Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program
Molecular Genetics and Genomics Program
Computational and Systems Biology Program

  • 314 747-8618

  • 8232

  • MRB - McKinley Research Building, Room 3316


  • The study of gene regulatory networks to dissect and engineer cell fate of clinically relevant tissues such as the liver

Research Abstract:

The in vitro generation of clinically relevant cells, such as neurons, cardiomyocytes, and hepatocytes, offers potential for regenerative therapy and permits disease modeling, toxicology testing and drug discovery. Current strategies aim to engineer cell fate by means of directed differentiation from a pluripotent state or by transcription factor-driven conversion between differentiated states. Directed differentiation protocols typically involve multiple steps, can be laborious, and commonly yield immature cells corresponding to embryonic stages of development rather than fully mature adult cells. In contrast, direct conversion is relatively straightforward and rapid but there is evidence for incomplete conversion, especially between divergent cell types.

Using a network biology approach, we recently found that cells generated by direct conversion do not faithfully recapitulate the target cell type. Original cell identity was not extinguished and the converted cells did not resemble fully mature cell types. Employing induced hepatocytes (iHeps) generated from fibroblasts as a prototypical conversion, our computational and functional analyses showed that iHeps behave as embryonic progenitors with the potential to functionally engraft both the liver and colon. We found that these engineered cells resembled mature colonic epithelium only after transplantation into the colon niche.

Our research focuses on the study of gene regulatory networks to dissect and engineer cell fate of clinically relevant tissues such as the liver. First, we aim to understand how transcription factor overexpression drives changes in the transcriptional program to remodel cell identity, and how we can exploit this to derive desired cell types. Second, we transplant engineered cells into the in vivo niche, tracking their maturation in order to understand the steps required to fully differentiate cells in vitro. Finally, we employ single cell transcriptomics to understand how cell fate is specified in the developing embryo, formulating a blueprint of cell identity to help engineer fate in vitro. Ultimately, we wish to translate new insights in cell fate specification into better human models of liver disease and eventually into the development of novel therapeutic strategies.

Selected Publications:

Morris SA*, Cahan PC*, Li H*, Zhao A, San Roman AK, Shivdasani RA, Collins JJ, Daley GQ. Dissecting Engineered Cell Types and Enhancing Cell Fate Conversion via CellNet. Cell. 2014 Aug 14;158(4):889-902.* Equal contribution.

Cahan PC*, Li H*, Morris SA*, Lummertz da Rocha E, Daley GQ, Collins JJ. CellNet: Network Biology Applied to Stem Cell Engineering. Cell. 2014 Aug 14;158(4):903-15. * Equal contribution.
Morris SA, Graham SJ, Jedrusik A, Zernicka-Goetz M. The differential response to Fgf signalling in cells internalized at different times influences lineage segregation in preimplantation mouse embryos. Open Biol. 2013 Nov20;3(11):130104

Morris SA, Daley GQ. A blueprint for engineering cell fate: current technologies to reprogram cell identity. Cell Res. 2013 Jan;23(1):33-48.

Morris SA, Gu Y, and Zernicka-Goetz M. Developmental plasticity is bound by pluripotency and the Fgf and Wnt signaling pathways. Cell Reports. 2012. Oct 25;2(4):756-65.

Morris SA*, Grewal S*, Barrios F*, Patankar SN, Strauss B, Buttery L, Alexander M, Shakesheff K and Zernicka-Goetz M. Dynamics of anterior-posterior axis formation in the developing mouse embryo. Nature Commun. 2012 Feb 14;3:673.

Last Updated: 12/7/2015 10:28:09 AM

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