Chemical Biology in the Sampson Lab

Work in the Sampson laboratory focuses on the relationship between protein structure and protein function, which is a critical aspect of post-genomic chemical biology research.  The functions of different protein systems ranging from bacterial cholesterol metabolism to mammalian fertilization have been elucidated using synthetic, analytical, and biochemical methods, including the development of methodology for the synthesis of new polymer structures. 

Sterol Oxidation.  The Sampson laboratory's work has defined the mechanisms of protein catalysts that function at the sterol:lipid interface.  These studies have evolved to undertake the elucidation of the mechanisms by which mycobacteria, e.g., M. tuberculosis, persist in their human host.  Her laboratory is pursuing a multi-pronged approach that includes elucidating enzyme function, establishing metabolite structure and activity to identify the substrates of key enzymes, identifying small molecules that interfere with the host immune response, and developing metabolomic methods to screen these pathways for inhibitors. 

Fertilization and Polymers.  Using synthetic peptides and polymers in combination with in vitro fertilization assays and photoaffinity labeling methods, protein-protein interactions that occur during mammalian fertilization have been identified.  Currently, new strategies for identifying partner proteins in protein complexes of low abundance are under investigation.  This work led to the development of new methodology for the synthesis of polymers.  Most notably, these methods enable the synthesis of precisely alternating polymers that are presently being applied to study the sperm acrosome reaction and energy transferring materials. 

Cancer Cell Migration.  Collaborative studies have resulted in the validation of the matrix metalloprotease hemopexin domain as a suitable target for inhibiting cell migration in cancer metastasis.  These studies are currently focused on developing improved inhibitors for in vivo use.