Susan Henning, PhD
Education and Training
University of Melbourne, BS, 1966
University of Melbourne, PhD, 1971
Stanford University, Postdoctoral, 1971-1974
Fels Research Institute, Postdoctoral, 1974-1975
Areas of Interest
The primary goal of our current work is to identify and characterize intestinal stem cells. Although the presence of these cells deep in the crypts of Lieberkuhn has been inferred for many years, to date they have never been isolated. We have deployed a novel sorting approach in order to isolate a “side population” (SP) of putative intestinal stem cells (Fig 1). The CD45-negative SP cells are cytokeratin positive, confirming their epithelial origin. Initial gene expression studies by quantitative RT-PCR showed the CD45-negative SP fraction to be enriched for the stem cell marker Musashi-1. More recent microarray analyses showed a broad pattern of gene expression consistent with a progenitor phenotype. Moreover, in situ hybridization of 36 transcripts enriched in the CD45-negative SP and 12 transcripts de-enriched, confirmed that SP sorting selects cells from the lower crypt (Fig 2). We are currently exploring both in vitro culture models and in vivo transplantation models to assess the capacity of CD45-negative intestinal SP cells for proliferation and differentiation. In addition, refinement of the isolation procedure is being pursued based on membrane markers identified by microarray. We believe that ultimately the isolation and transplantation techniques developed in this project should have two applications: a) new therapies for various conditions in which the bowel is damaged; and b) use of the intestine as a site for gene therapy.