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Dr. Karen. J. Colley
Professor

  • Ph.D. 1987, Washington University, St. Louis
  • Postdoctoral studies¬†University of California, Los Angeles

Research Interests:
The modification of proteins with sugars (glycans) mediates and modulates a vast array of protein functions and cell interactions. The glycan profile of cells is different during development, in the adult, and in disease states, and impacts the extent of cell migration, cell adhesion, and related signaling events observed during these times. Our current focus is on the process of polysialylation that is catalyzed by two polysialyltransferases (polySTs), ST8SiaII (STX) and ST8SiaIV (PST). Polysialic acid (polySia) is unique in that it is found on a small group of mammalian proteins, with the neural cell adhesion molecule (NCAM) being its major carrier. As a highly negatively charged, anti-adhesive glycan, polySia is absolutely required for proper brain development, as well as processes in the adult requiring on-going cell migration and plasticity, such as learning and memory. The up-regulation of polySia promotes neural repair and regeneration, and polySia is highly expressed on several metastatic cancer cells where it is believed to enhance their growth and invasiveness.

The polySTs recognize an acidic surface
on the FN1 domain of NCAM that positions
them to polysialylate two N-glycans on the
adjacent Ig5 domain. Recent results
indicate that basic residues at the stem-
catalytic domain border of the polySTs
mediate their recognition of NCAM,
SynCAM 1 and neuropilin-2.

Our current focus is on the process of polysialylation that is catalyzed by two polysialyltransferases (polySTs), ST8SiaII (STX) and ST8SiaIV (PST). Polysialic acid (polySia) is unique in that it is found on a small group of mammalian proteins, with the neural cell adhesion molecule (NCAM) being its major carrier. As a highly negatively charged, anti-adhesive glycan, polySia is absolutely required for proper brain development, as well as processes in the adult requiring on-going cell migration and plasticity, such as learning and memory. The up-regulation of polySia promotes neural repair and regeneration, and polySia is highly expressed on several metastatic cancer cells where it is believed to enhance their growth and invasiveness.

We are taking biochemical, structural, and cell biological approaches to understand how the polySTs specifically recognize their substrates. We have identified sequences in both NCAM and the polySTs that are required for specific recognition and polysialylation, and are expanding these studies to other substrates such as neuropilin-2 and SynCAM 1. We hope that our results will allow us to develop strategies to either enhance or block polysialylation during development, regeneration and disease.

Other interests of the lab include:

  • The mechanisms underlying the Golgi localization of glycosyltransferases and nucleotide sugar transporters.
  • Analysis of the structure and function of glycosyltransferases and nucleotide sugar transporters.

Contact

Email: karenc@uic.edu
Site:
Office: 312-996-7756
Lab: 312-996-8108

Publications

View Publications on PubMed

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