Cells must carefully implement many physical and chemical inputs so they can function properly. For example, when cells receive chemical cues to divide, intracellular signaling pathways are stimulated that lead to replication of cellular components and the cells eventually exert forces which segregate these components and separate the cells. Also, pathogenic organisms or malignant cells polarize and exert forces as they invade through tissues in response to homing signals. Likewise, during development of an organism, cells respond to soluble and immobilized factors in their environment and migrate to a precise location in the embryo. Our goal is to dissect the chemical signaling pathways and characterize how quantitative changes in the flow of signals can control a wide variety of cellular processes. With this information we will design strategies to stimulate or inhibit cellular signaling pathways either at the chemical or physical level, and thereby regulate cell functions.
We study how cell-host interactions influence virulence of the human pathogen Candida albicans. Genetic screens are used to identify adhesion receptors that bind human cells or materials commonly used in implanted medical devices. Then, we use molecular and cell biology to identify how expression and activity of these adhesion receptors is regulated by external cues, such as host factors, environmental conditions, and growth in a biofilm. Then, we test the relevance of these adhesion receptors in animal models. Finally, we use this information to develop novel antifungal strategies and to design materials that resist fungal adhesion and biofilm growth.
Human embryonic stem cells (hESCs) hold tremendous potential for use in tissue engineering applications because of their virtually unlimited capability to self-renew and their ability to differentiate into any cell type found in the adult. Thus, under the proper conditions, it is possible to generate a limitless supply of a desired cell type from a single, safe source. One of our goals in hESC research is to develop methods to guide differentiation along desired lineages to generate cells for tissue engineering applications. We use growth factors, cytokines, and other signaling molecules to guide hESCs along developmental pathways to generate skin cells, then compare the function of these cells to “normal” adult skin cells. We also investigate the ability of these hESC-derived skin cells to form appropriate three-dimensional structure in skin equivalent constructs. Another goal of our hESC research program involves developing bioprocessing methods to facilitate growth of pure self-renewing populations of hESCs. In future clinical-based applications, large numbers of these undifferentiated cells will be required. We are discovering signals that maintain hESCs in an undifferentiated state then using this information to design strategies for the growth and preservation of these cells.
Understanding how chemical and physical signals affect cell function requires parallel high-throughput methods to assess the activity of intracellular signal transduction pathways. We are developing protein arrays in which we immobilize reaction substrates in an inert hydrogel, then expose these substrates to cellular extracts and quantify the activity of enzymes in the extract by the rates of modification of the immobilized substrates. Key aspects of this project include developing new methods for high-density immobilization of active proteins and peptides and development of direct techniques for quantifying substrate modification.
Copyright 2005 The Board of Regents of the University of Wisconsin System
Date last modified:
12-Sep-2005
Date created: 8-Sep-2005
Content by: palecek@engr.wisc.edu
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