Biological and Biomedical Science
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Marianne Wessling-Resnick

Department of Genetics and Complex Diseases
Harvard School of Public Health
Division of Biological Sciences
Building 2, Room 123
665 Huntington Avenue
Boston, MA 02115
Tel: (617) 432-3267
Fax: (617) 432-5236
Email: wessling@hsph.harvard.edu
5 postdoctoral fellows, 1 graduate student

 Marianne Wessling-Resnick

Our laboratory is interested in the mechanisms and regulation of iron transport.  We use medium throughput screens to discover small molecule inhibitors that block different iron transport pathways.  We perform chemical genetic screens for selective inhibitors of different pathways of iron transport using combinatorial libraries and characterize the compounds identified to block iron uptake with highest potency, developing structure-activity profiles on compounds of interest.  Our ultimate goal is to identify the target of action, and these efforts have recently revealed how ebselen blocks uptake mediated by divalent metal transporter-1 by altering cellular redox potential and how ferristatin inhibits iron uptake by the transferrin-transferrin receptor pathway by stimulating a novel pattern of endocytosis.

 

We are also interested in how regulation of iron transport may alter uptake of other metals, and we have focused on elements involved in the olfactory transport of manganese, a neurotoxin. The goals of this project are to determine the distribution of intranasally instilled manganese in the brains of control and iron-deficient rats using magnetic resonance imaging.  To monitor neurotoxicity, we determine motor coordination and learning/memory capacity of exposed and non-exposed cohorts using roto-rod and bridge-walking, as well as Morris water maze tests. 

 

References:

  • Wetli H, Buckett PD, Wessling-Resnick M. Chemical genetic screening identifies the selanazal drug ebselen as a potent inhibitor of DMT1-mediated iron uptake. Chem Biol 2006; 13: 965-972.
  • Thompson K, Molina R, Donaghey T, Schwob JE, Brain JD, Wessling-Resnick M. Olfactory uptake of manganese requires Divalent Metal Transporter-1 (DMT1) and is enhanced by anemia. FASEB J 2007; 1:223-230.
  • Horonchik L, Wessling-Resnick M. The Small Molecule Transport Inhibitor Ferristatin (NCI306711) Promotes Degradation of the Transferrin Receptor. Chem Biol 2008; 15:647-653.