Samantha A. Morris, Ph.D.
Developmental Biology and Genetics
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.
- 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.
- Morris SA and Zernicka-Goetz M. Formation of distinct cell types in the mouse blastocyst. Mouse Development: From Oocyte to Stem. Springer. Jacek Z. Kubiak (Ed.). Results Probl Cell Differ. 2012;55:203-17
- Morris SA. Cell fate in the early mouse embryo: Sorting out the influence of developmental history on lineage choice. Reprod Biomed Online. 2011 Jun;22(6):521-4
- Zernicka-Goetz M, Morris SA, Bruce AW. Making a firm decision: multifaceted regulation of cell fate in the early mouse embryo. Nat Rev Genet. 2009 Jul;10(7):467-77.
- Morris SA, Teo RT, Li H, Robson P, Glover DM, Zernicka-Goetz M. Origin and formation of the first two distinct cell types of the inner cell mass in the mouse embryo. Proc Natl Acad Sci USA. 2010 Apr 6;107(14):6364-9
- Morris SA, Almeida AD, Tanaka H, Ohta K, Ohnuma S. Tsukushi modulates Xnr2, FGF and BMP signaling: regulation of Xenopus germ layer formation. PLoS One. 2007 Oct 10;2(10):e1004
Education and Professional Experience
- 7/15-present Assistant Professor, Department of Genetics, Department of Developmental Biology, Washington University School of Medicine, St. Louis, USA
- 11/11-7/15- Postdoctoral Fellow, Boston Children’s Hospital, Harvard Medical School, USA Laboratory of Professor George Daley, MD, PhD
- 07/07-10/11 Postdoctoral Fellow, Gurdon Institute Department of Physiology, Development and Neuroscience, University of Cambridge, UK Laboratory of Professor Magdalena Zernicka-Goetz, PhD
- 10/02-09/06 PhD, Department of Oncology Clare College, University of Cambridge, UK Laboratory of Professor Shin-ichi Ohnuma, PhD
- 9/99-7/02 Bachelor of Science, Department of Biochemistry Imperial College of Science, Technology, and Medicine, University of London Graduated First Class, with honors
Research and Professional Experience
- 11/11-7/15 Laboratory of Professor George Daley, MD, PhD (Boston Children’s Hospital). Mapping the transcriptional landscape of development and cell fate engineering via transcription factor mediated direct conversion.
- 07/07-10/11 Laboratory of Professor Magdalena Zernicka-Goetz, PhD (University of Cambridge). Preimplantation mouse development: transcription factor and cell signal mediated specification of cell fate and regulation of development. Formation of postimplantation signaling centers.
- 10/02-06/07 Laboratory of Professor Shin-ichi Ohnuma, PhD (University of Cambridge). TGF-β signaling and cell fate specification in Xenopus laevis.
- 05/01-10/01 Laboratory of Jane Saffell, PhD (Imperial College London). FGF signaling in neural development.
- 03/02-06/02 Laboratory of Professor Patricia Salinas, PhD (Imperial College London). Wnt signaling in developing neurons.
Honors and Awards
- 11/14 Sanofi-Cell Research ‘Outstanding Review Article Award 2013’, for Morris and Daley, “A blueprint for engineering cell fate: current technologies to reprogram cell identity.” http://www.nature.com/cr/journal/v24/n11/full/cr2014140a.html
- 01/13 Cell Reports, ‘Best of 2012’ for Morris et al., “Developmental plasticity is bound by Fgf and Wnt signaling pathways.”
- 11/09 Runnström Medal for Wenner Gren Institute Lecture, Stockholm University.
- 09/09 Gurdon Institute, University of Cambridge, First Place Poster Prize
- 09/05 Department of Oncology, University of Cambridge, First Place Poster Prize
- 11/00 Eric Potter Clarkson prize for best use of intellectual property
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- David M. Ornitz, M.D., Ph.D.
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- Adjunct Faculty
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