Susan Kirkland, PhD
Chemical Biology & Therapeutics
Harnessing stem cell signaling to promote epithelial regeneration
My group aims to transiently regulate stem cell fate decisions in primary epithelial cells for therapeutic benefit in regenerative medicine. Rapid cell turnover seen in many adult epithelia is fueled by a small population of tissue epithelial stem cells, which self-renew and provide differentiated progeny to match tissue needs. Epithelial homeostasis depends on a tightly-regulated balance between stem cell renewal and lineage commitment that is maintained by both intrinsic and extrinsic signaling from the microenvironment. The main scientific questions within my lab focus on stem cell fate regulation and how this relates to survival. One aim is to identify novel molecular mechanisms regulating epithelial stem cell fate, with a focus on the Beta1 integrin family of cell-matrix receptors. An intrinsic property of adult epithelial stem cells is their ability to survive in isolation, the basis of the classic clonogenic assay, while more differentiated cells require cell-cell contact for survival. Therefore we will also pursue mechanisms that underpin cross talk between cell-matrix and cell-cell adhesion signaling to maintain the “stemness” phenotype. Our group has expertise in stem cell biology, and we have established models and assays to dissect the biology of epithelial stem cells. In addition, screens and LMW compounds already shown to regulate stem cell fate will be a valuable resource to enhance discovery and expedite project innovation and progression. The knowledge generated by our studies will have significance both for regenerative medicine and cancer cell biology.
Type I collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells.
Br. J. Cancer 2009 101: 320-326.
Alpha2Beta1 integrin regulates lineage commitment in multipotent human colorectal cancer cells.
Kirkland SC and Ying H
J Biol Chem 2008 283: 27612-9.
Clonal origin of columnar, mucous and endocrine cell lineages in human colorectal epithelium.
Cancer 1988 61: 1359-63.
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