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Our laboratory investigates the structural basis for recognition, biochemical function and biological specificity of proteins and nucleic acids. Specifically, we study systems involved in bacterial pathogenesis, cell signaling, and cancer at the molecular level. Rather than focusing on specific techniques, we take a problem-oriented approach and use whichever techniques are necessary to answer the question at hand. Often, this requires complementary application of structural approaches including spectroscopy, scattering, crystallography and microscopy. We also prioritize tight coupling of our research to functional analysis. This strategy is by nature very collaborative and collegial, and has stimulated involvement in many multi-investigator projects. The following lists key questions that we are addressing, including links to papers that provide an overview of the specific research projects. You can find a complete list of our publications here.

Key questions:

  1. What is the mechanism of action of the multi-protein nuclear excision repair (NER) machinery and the basis for mal-function caused by disease-associated mutations? Is suppression of the DNA damage response, or NER alone, a viable strategy to enhance the efficacy of anti-cancer therapeutics?
  1. How is the gene duplication phase of DNA replication initiated? How do replicative polymerases communicate?
  2. What are the mechanisms of action of calprotectin in the innate immune response to host infection by pathogens? What are the means by which microorganisms pirate essential trace metals from calprotectin?
  1. How do S100 proteins activate the receptor for advanced glycation end products (RAGE)? Is inhibition of RAGE-ligand interactions a viable strategy to suppress the chronic inflammation symptoms of diabetics?
  1. How does intracellular calcium signaling regulate cardiac ion channels? How do mutations affecting the calcium sensing apparatus in cardiac ion channels and in calmodulin cause cardiac arrhythmia syndromes?
  1. What are the molecular mechanisms that drive ubiquitin signaling?