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Andreas G Seyfang
Associate Professor

University of South Florida

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Memberships

Begin End Membership Type Organization
2000 Member American Society for Microbiology (ASM)
2000 Member American Society for Biochemistry and Molecular Biology (ASBMB)
2006 Member Society for Neuroscience (SfN)
2000 Member American Association for the Advancement of Science (AAAS)
2012 Member International Association of Medical Science Educators (IAMSE)

Peer Review Positions

Title Begin End Review Type Organization
Louisiana Board of Regents/National Science Foundation (NSF) 2005 2007 Funding Louisiana Board of Regents/National Science Foundation grants review program
US Department of Veterans Affairs, Research & Development Program 2007 2007 Funding US Department of Veterans Affairs, Research & Development Program
American Heart Association, Study Section R2 (Immunology & Virology; Microbiology/Microbial Pathogenesis) 2008 2010 Funding American Heart Association, Study Section R2 (Immunology & Virology; Microbiology/Microbial Pathogenesis)
Swiss National Science Foundation (SNSF) grants review 2009 2009 Funding Swiss National Science Foundation (SNSF) grant review programme
US Department of Agriculture (USDA-NRI) 2003 2003 Funding US Department of Agriculture (USDA-NRI) Competitive Grants Program, Animal Health & Well-Being Program
American Heart Association, Southern & Ohio Valley Study Section 4B 2004 2007 Funding American Heart Association, Southern & Ohio Valley Study Section 4B (Cell Transport & Metabolism; Immunology & Microbiology)
USUHS (Uniformed Services University of the Health Sciences) 2004 2004 Funding USUHS (Uniformed Services University of the Health Sciences) Intramural Research Program
The Wellcome Trust, London (Infection & Immunology study section) 2004 2004 Funding The Wellcome Trust, London (Infection & Immunology study section)

Other Professional Activities

Laboratory of Medical Microbiology and Molecular Parasitology:

Research in the Seyfang laboratory focuses on two major projects (i) membrane permeases (transporters) as target for drug delivery and (ii) cytochrome b5 reductase as enzymatic drug target in opportunistic microbial pathogens including protozoan parasites and nosocomial and neuro-pathogenic fungi (Candida albicans, Cryptococcus neoformans).

Membrane transport proteins in pathogenic microorganisms are of particular interest as they form the primary interface between microorganism and human host to interfere with their physiological functions. As the gatekeepers of the cell, these permeases control specificity and quantity of nutrient acquisition from the host and hence are an attractive pharmacological target for delivery of cytotoxic and parasite-specific substrate analogues and drugs.

We are studying the biochemistry and molecular pharmacology of membrane transporters (permeases) for essential nutrients and vitamins as targets for rational drug design and as vehicles for drug delivery in opportunistic microbial pathogens including protozoan parasites (Leishmania and trypanosomes), which include the etiological agents of devastating and often fatal diseases such as kala-azar/leishmaniasis, Chagas’ heart disease and sleeping sickness. Furthermore, our laboratory studies the biochemistry and pharmacology of membrane transport in the opportunistic pathogenic fungi Candida and Cryptococcus neoformans, which are important oral, nosocomial and/or neuro-pathogenic pathogens and of increasing medical significance owing to the HIV disease/AIDS pandemic and the development of drug resistance.

We have chosen the myo-inositol transporters in these pathogens as a novel target since inositol is an essential precursor for the glycosyl-phosphatidylinositol (GPI)-anchors of protective and/or immunomodulatory surface molecules in parasitic protozoa and pathogenic fungi, and GPI-anchored surface molecules are about 1000 times more abundant on the cell surface of these parasites than on mammalian cells. Hence, we are employing a multi-disciplinary approach of biochemistry, proteomics, molecular pharmacology and genetics to probe the structure-function relationship, substrate/drug selectivity, protein-protein interaction, and significance for microbial pathogenicity of these membrane proteins at the molecular level in both in vitro culture and animal models.

Our laboratory could show that inositol transport in Leishmania, trypanosomes and the two pathogenic fungi Candida and Cryptococcus is active and proton-coupled but sodium-independent, in contrast to the sodium-coupled inositol transport in the intestine and kidney of the human host. Using drug design based on the specificity of substrate recognition of the Leishmania model myo-inositol/H+ transporter MIT, we have started to develop fluorinated inositol analogues and could already show strong inhibition of cell growth in Leishmania by the inositol analogue 3-fluoro-myo-inositol.

A second project investigates cytochrome b5 reductase as enzymatic drug target in these opportunistic microbial pathogens. Cytochrome b5 reductase (Cb5r) plays an important role in P450-mediated detoxification of xenobiotics and drugs, lipid biosynthesis, and the synthesis of cholesterol (humans) or ergosterol (fungi, Leishmania and Trypanosoma cruzi). Hence we use recombinant Cb5r protein for biochemical, structural and pharmacological studies and in silico modeling as a novel pharmacological target in these opportunistic microbial pathogens.

TECHNIQUES that are employed in the laboratory, include all aspects of protein biochemistry and molecular biology, proteomics, microarray and real-time PCR gene expression analysis, site-directed mutagenesis, targeted gene disruption and reverse genetics, pharmacology of microbial drug targets, molecular parasitology, and medical microbiology.

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