Primary AppointmentAssistant Professor, Biomedical Engineering
- BA, Chemistry, Hamilton College, Clinton NY
- PhD, Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Advancement in the design of imaging agents; molecular imaging and radiological sciences.
My laboratory currently uses several different strategies, including phage display, small molecule display on nanoparticles, and SELEX, to identify lead candidates for the development of amplifiable targeted imaging agents. In one specific example, using phage display, we successfully developed a magneto-optical probe targeting early-stage atherosclerotic lesions. We have shown that VCAM-1 expression in inflamed endothelium could be specifically identified optically and via MRI in mouse models of atherosclerosis. The utility of this probe extended to the in vivo detection of the therapeutic efficacy of statin treatment for lowering VCAM-1 levels in plaque. In addition to phage display, we have also created nanoparticle libraries that achieve specificity through multivalent modification with small molecules. We were able to rapidly screen the library against a variety of cell lines and have discovered a series of novel nanoparticles with specificity for endothelial cells, activated human macrophages or pancreatic cancer cells. The method and described materials could have important applications for the development of functional nanomaterials for biology, functional differentiation of cell lines, and targeting.
A second research interest is target identification of novel imaging agents identified through the above screens and determining their importance in pathologies. For example, we previously identified the peptide sequence RPMC as one, which specifically targets colon cancer and subsequently demonstrated it to be a target for the alpha5-beta1 integrin. Similarly, we identified VCAM-1 targeted peptide sequences with homology to the protein SPARC or osteonectin, which has been shown to play an important role in tumorogenesis and metastasis. The interaction of VCAM-1 and SPARC provided important insights into the mechanisms of transendothelial leukocyte migration.