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Amanda Fenner

Mentor: Robert J. Kerns, PhD

Year Entered Into Program: 2006

PhD Institution: University of Iowa, 2011

Affiliations

  • Medicinal and Natural Products Chemistry

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.

Awards

  • 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

Publications

  1. Fenner AM, Kerns RJ.:  Synthesis, separation, and characterization of amphiphilic sulfated oligosaccharides enabled by reversed-phase ion pairing LC and LC-MS methods. Carbohydr Res. 346(17):2792-800, 2011.  PMCID: PMC3221801
  2. Fink BD, Herlein JA, Yorek MA, Fenner AM, Kerns RJ, Sivitz WI.: Bioenergetic effects of mitochondrial-targeted coenzyme Q analogs in endothelial cells. J Pharmacol Exp Ther. 342(3):709-19, 2012.  PMCID: PMC3422527
  3. Fenner AM, Oppegard LM, Hiasa H, Kerns RJ.: Selective inhibition of bacterial and human topoisomerases by N-arylacyl O-sulfonated aminoglycoside derivatives. ACS Med Chem Lett. 4(5):470-474, 2013.  PMCID: PMC3694624
  4. Craciun I, Fenner AM, Kerns RJ.:  N-Arylacyl O-sulfonated aminoglycosides as novel inhibitors of human neutrophil elastase, cathepsin G and proteinase 3. Glycobiology 26(7):701-709, 2016.  PMCID: PMC4976519

Research