Optical Radiology Labs at Washington University in St. Louis School of Medicine
W. Barry Edwards

W. Barry Edwards

Assistant Professor
314-362-6943
edwardsb@mir.wustl.edu
Washington University School of Medicine
Department of Radiology
Campus Box 8225
4525 Scott Avenue
St. Louis, MO 63110

Education

  • Univ. of North Carolina, Asheville, NC B.S.1985 chemistry
  • Florida State Univ. M.S.1990 organic chemistry
  • Washington University Ph.D. 1999 bioorganic chemistry

Research Interests

We are interested in imaging proteolytic activity of tumor-related enzymes. Specifically, we are targeting MMP-2 and MMP-9, two matrix metalloproteinases that have been implicated in tumor metastasis and are functionally upregulated in many human tumors. The targeting agent is a highly specific optical probe based on an enzyme substrate developed in the laboratory of collaborator Gregg Fields. The probes are triple helical peptides (THPs) that function as “mini-collagens” bearing a pair of near infrared dyes flanking the hydrolysis sites. The close proximity of the dyes results in quenched fluorescence. After MMP mediated hydrolysis and subsequent denaturation of the triple helix, the fragments migrate apart and fluorescence is released. Thus, fluorescence can be directly related to proteolytic activity. If successful, these types of probes may be useful in directing MMP inhibitor therapy.

Additionally, we are developing peptides for imaging prostate specific membrane antigen (PSMA) bearing a chelator (DOTA) for radiometals such 111In or 68Ga for either SPECT or PET imaging, respectively, as well as a near infrared (NIR) dye, cypate, for imaging tumors or defining tumor margins during surgery by NIR spectroscopy. PSMA expression is limited to the prostate and is up-regulated in prostate tumors. Imaging of PSMA is currently hindered by a lack of probes. Labeled monoclonal antibodies as well as small molecules are under investigation, but as of yet, no peptides with suitable affinity for molecular imaging have been discovered. Peptides offer the promise of favorable pharmacokinetics and toleration of a wide variety of imaging reporters, such as the aforementioned NIR-dyes and radioisotopes. A logical starting place for a peptide-based imaging agent would be the natural ligand of PSMA, if it were a polypeptide and if it were known. The only way to discover a peptide for imaging of PSMA is through screening combinatorial peptide libraries. We will start with a library of phage displayed peptides, taking advantage of high diversity of peptides within the library, and screen the library against the soluble form of PSMA. In an innovative approach, the binding sequences from the phage library will be used to direct the bias of the synthetic library towards binding peptides. Another innovation is the incorporation of DOTA and cypate during the selection process with the synthetic library, thus obviating the need to optimize the labeling sites of the affinity selected peptides. If successful, the union of phage display and synthetic combinatorial libraries has the potential to provide a candidate for molecular imaging of PSMA for diagnostic purposes.

For an up to date list of Dr. Edwards' publications please see his entry on PubMed.

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