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Washington University in St. Louis - School of Medicine
Department of Developmental Biology

Samantha A. Morris, Ph.D.

Assistant Professor

Washington University School of Medicine
660 S. Euclid Avenue
Campus Box 8103
Saint Louis , MO 63110

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Research Interests

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

 

Samantha A. Morris, Ph.D.

Assistant Professor

Washington University School of Medicine
660 S. Euclid Avenue
Campus Box 8103
Saint Louis , MO 63110

Links

Other Information


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