Research Interests:


Our research is focused on using organic synthesis and enzymes
coupled state of the art biophysical techniques such as fluorescence, NMR,
mass spectrometry, and microcalorimetry to creatively assemble new tools for
studying biology.

Currently we are engaged in three main areas of study:

1) New approaches to the study of glycosaminoglycans:

Using commercially available and cloned enzymes defined Glycosaminoglycan fragments will be generated and used as synthetic starting materials.  We are focused on making substrates to define the activities of the important cancer related class of mammalian glycosaminoglycan degrading enzymes, the Hyaluronidases.  Future goals include making semi-synthetic Heparin and inhibitors of the Chemokines.
Synthesis of Glycosaminoglycan sensors based on peptide scaffolds.  It is extremely challenging to define the sulfation patterns of glycosaminoglycans. We seek to synthesize fluorescent sensors of specific glycosaminoglycan sulfation patterns based on naturally occurring glycosaminoglycan-binding elements.  Using Fluorescent Resonance Energy Transfer (FRET), environmentally sensitive fluorophores and peptide design new GAG sensors are being developed.

2) Defining the roles of Inositols in Amyloid Disorders:

Recently it was found that inositols dramatically affect the aggregation pathways of amyloid disorders.  Currently the molecular role of these compounds in these diseases is unknown.  We are in the process of synthesizing inositol derivatives to define the binding sites on the Amyloid aggregates.  We are currently assaying these compounds in a novel single fibril assay to determine their effects on amyloid fibril formation.

3) Biofilm formation and modulation:

Biofilms account over 80% of human bacterial infections. Until recently the molecular details of biofilm formation have been limited.  We are engaged in the study of key enzymes in the biofilm forming process. These studies involve the synthesis of oligosaccharide substrates of the enzymes crucial to biofilm formation.  These compounds allow a detailed kinetic analysis of the enzymes mechanism and the development of inhibitors to biofilm formation.  In the future we aim to develop a new class of antibiotics which target biofilm formation.