Pharmacology

Amanda Fenner

Mentor: Robert Kerns, PhD

Year Entered Into Program: 2006-2011

PhD Institution: UCSD, Scripps Institution of Oceanography

Research Description

Heparan sulfate (HS) is a highly-charged, polysulfonated, polysaccharide located on the surface and in the extracellular matrix of mammalian cells. HS plays a profound role in the recognition of, adhesion to, and/or infectivity of host cells by many pathogenic organisms including plasmodia, yersina pestis, listeria monocytogenes, and giardia lamblia and in the progression of non-pathogenic diseases such as cancer, Alzheimer’s, and atherosclerosis. Molecules that selectively bind HS-binding proteins and block HS-protein interactions involved in host-pathogen interactions are needed for the development of therapeutic agents to block invasion, replication and/or virulence of these diseases. The Kerns lab has recently identified chemically-modified heparin derivatives that selectively bind and block HS-binding proteins. My research is focused on the design and synthesis of N-acylated/O-sulfonated derivatives of naturally occurring amino sugars as novel, selective inhibitors of HS-protein interactions. I will also employ enzymatic depolymerization of naturally occurring polysaccharides to create size-defined oligosaccharides for further chemical modification as inhibitors of HS-binding proteins. HS-protein binding studies will be performed to evaluate the modified saccharides as potential inhibitors of host-pathogen interactions as well inhibitors of heparanase and fibroblast growth factors, which are targets for cancer treatment. Ultimately, my goal is to employ my chemically modified and/or biocatalytically-derived saccharides that selectively bind bacterial surface proteins as chemical probes to study HS binding versus HS bridging mechanisms in bacteria-host cell interactions.

Publication(s)

1.   Balunas, M.J, Linington, R.G., Tidgewell, K., Fenner, A.M., Ureña, L., Della Togna, G., Kyle, D.E., Gerwick, W.H.:  Dragonamide E, a Modified Linear Lipopeptide from Lyngbya majuscula with Antileishmanial Activity, J Nat Prod73, 60-66, 2010.  

Award(s)

  • NIH T32 Pharmacological Sciences Training Grant, 2007-2009
  • Awarded AFPE Predoctoral Fellowship, 2008-2010
  • Graduate Incentive Fellowship, Univ of Iowa, 2009-2010
  • Recipient of American Chemical Society Pre-doctoral Fellowship, 2009-2010
  • Recipient, Dr. Eunice Schuytema Beam Travel Grant, part of UI WISE Program, 2010