To exploit the full potential of human pluripotent stem (hPS) cells for regenerative medicine, developmental biology, and drug discovery, defined, reproducible conditions for hPS cell propagation and differentiation must be identified. The long-term objective of the proposed research is to address this need by designing and implementing chemical biology strategies. The three Aims have been devised to elucidate how specific soluble and insoluble chemical cues act together to control cell fate decisions. In the past grant period, we synthesized a surface array and screened it to discover peptide-substituted surfaces that promote hPS cell self-renewal. The most effective substrates interact with glycosaminoglycans.
In Aim 1, we shall investigate the role of glycosaminoglycans in hPS cell pluripotency.
In Aim 2, we shall employ our surface array screen to identify insoluble signals (peptide-derived) that act in concert with soluble signals to direct hPS cell differentiation. In Am 3, we shall synthesize a series of biocompatible polymers that vary in cell binding groups and elasticity. Using these tools, we shall examine how hPS cells respond to distinct combinations of soluble, insoluble, and mechanical cues. In pursuing these Aims, we shall employ methods and ideas from organic chemistry, peptide chemistry, stem cell biology, and chemical biology.

Public Health Relevance

Human pluripotent stem cells can be used to identify drugs for key human diseases, and they are promising potential sources of more specialized human cells (e.g., heart cells or brain cells) for treating disease. To obtain each desired type of specialized cell, scientists must learn what cues to give the hPS cells so that they reproducibly differentiate into the specific cell type needed. The research proposed is designed to determine how to deliver the right chemical cues to control the differentiation of hPS cells into desired cell types

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Special Emphasis Panel (ZRG1 (02))
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Marino, Pamela
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University of Wisconsin Madison
Schools of Earth Sciences/Natur
United States
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Wrighton, Paul J; Kiessling, Laura L (2015) Forces of Change: Mechanics Underlying Formation of Functional 3D Organ Buds. Cell Stem Cell 16:453-4
Hudson, Kieran L; Bartlett, Gail J; Diehl, Roger C et al. (2015) Carbohydrate-Aromatic Interactions in Proteins. J Am Chem Soc 137:15152-60
Bennett, Nitasha R; Zwick, Daniel B; Courtney, Adam H et al. (2015) Multivalent Antigens for Promoting B and T Cell Activation. ACS Chem Biol 10:1817-24
Sheridan, Rachael T C; Hudon, Jonathan; Hank, Jacquelyn A et al. (2014) Rhamnose glycoconjugates for the recruitment of endogenous anti-carbohydrate antibodies to tumor cells. Chembiochem 15:1393-8
Musah, Samira; Wrighton, Paul J; Zaltsman, Yefim et al. (2014) Substratum-induced differentiation of human pluripotent stem cells reveals the coactivator YAP is a potent regulator of neuronal specification. Proc Natl Acad Sci U S A 111:13805-10
Courtney, Adam H; Bennett, Nitasha R; Zwick, Daniel B et al. (2014) Synthetic antigens reveal dynamics of BCR endocytosis during inhibitory signaling. ACS Chem Biol 9:202-10
Wrighton, Paul J; Klim, Joseph R; Hernandez, Brandon A et al. (2014) Signals from the surface modulate differentiation of human pluripotent stem cells through glycosaminoglycans and integrins. Proc Natl Acad Sci U S A 111:18126-31
Fishman, Joshua M; Kiessling, Laura L (2013) Synthesis of functionalizable and degradable polymers by ring-opening metathesis polymerization. Angew Chem Int Ed Engl 52:5061-4
Kiessling, Laura L; Kraft, Matthew B (2013) Chemistry. A path to complex carbohydrates. Science 341:357-8
Kiessling, Laura L; Grim, Joseph C (2013) Glycopolymer probes of signal transduction. Chem Soc Rev 42:4476-91

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