“Ground State” Adult Stem Cells in Regenerative Medicine, Disease



“Ground State” Adult Stem Cells in Regenerative Medicine, Disease
Department of Microbiology & Immunology Programme
Seminar Series … May 2015
Day / Date / Time
Monday 4 May 2015
“Ground State” Adult Stem Cells in Regenerative
Medicine, Disease Modeling, and Cancer
Therapeutics Discovery
Profs dfad f
Professor Frank McKeon
National University of
Singapore (NUS),
Department of
Seminar Room @
5 Science Drive 2,
Blk MD4A, Level 2,
Singapore 117545
Genome Institute of Singapore
MultiClonal Therapeutics, Inc.
Prof Nicholas Gascoigne
Induced pluripotent stem cells (iPSCs) dominate prospective efforts in regenerative
medicine and disease modeling despite organic features that limit their utility. In contrast,
resident adult stem cells, especially those of regenerative columnar epithelia such as the
gastrointestinal tract, liver, pancreas, and kidney, have been largely ignored because of
technical barriers that prevent their cloning and propagation. The lab has now developed
robust methods for cloning the adult stem cells from these tissues in their most immature,
ground state. This technology is beginning to unravel basic properties of the adult stem
cells including their unlimited expansion ability and epigenetic memory of both lineage
commitment and in some cases chronic disease states. Moreover, ground state stem cells
show a remarkable ability to assemble complex structures similar to mature tissues
without external guidance. These properties, combined with the ease of generating stem
cells from endoscopic biopsies, suggest that patient-specific, ground state stem cells
represent a viable alternative to iPSCs in regenerative medicine and disease modeling. In
addition to ground state stem cells of regenerative epithelia, this technology has been
applied to stem cells of highly aggressive epithelial cancers such as those of the
esophagus, stomach, pancreas, liver, and ovary. From “libraries” of such cancer stem
cells from individual cases the immense heterogeneity of these tumors can be
reconstructed from a genomics analysis of the individual constituent clones. From the
therapeutic standpoint, these libraries enable the discovery of intrinsically (pre-therapy)
resistant clones that most likely mount recurrent disease following standard-of-care
chemotherapy. Such approaches have tremendous potential for tailoring cancer therapies
to each patient.
About our speaker
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Frank McKEON and Wa XIAN jointly oversee a highly interactive group devoted to the
cloning of stem cells of regenerative tissues and using advanced technologies to understand
the genetics of their self-renewal, commitment, and differentiation. They have a strong
interest in determining pathways by which these stem cells might contribute to regenerative
medicine especially for lung and liver, and pancreatic diseases. In addition, they have a strong
interest in precursors of cancers- in particular early lesions that lead to high-grade ovarian
cancers as well as in the origins of intestinal metaplasias which precede esophageal, gastric,
and pancreatic adenocarcinoma. Frank McKeon was born in New Haven, Connecticut, and
was an undergraduate at Pomona College. He did his doctoral and postdoctoral studies in
Biochemistry and Biophysics with Prof. Marc Kirschner at the University of California, San
Francisco. He worked at Harvard University for more than twenty years and joined the
Genome Institute of Singapore as a Senior Group leader in 2008. He spent three years at
Jackson Laboratory for Genomic Medicine as director of Quantitative Cell Biology before his
present position shared between MultiClonal Therapeutics and the Genome Institute of
Singapore. He has worked in several areas of cell biology including nuclear lamin dynamics,
the spindle assembly checkpoint monitoring chromosome segregation, the role of NF-AT
transcription factors in T cell activation, and mouse models of the p53 homologs p63 and p73.

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