Dr. Tomas Ganz's research focuses on antimicrobial peptides in innate immunity and on the connection between innate immunity and iron metabolism.
Multicellular organisms, including humans, employ potent and rapidly acting antimicrobial defense mechanisms that are mediated by small peptide antibiotics. Unlike conventional antibiotics produced by specialized metabolic pathways of bacteria and fungi, the antibiotics of higher eukaryotes are generated by post-translational processing of gene-encoded prepropeptides. The microbicidal granules of phagocytic cells and the secretions on mucosal surfaces are particularly rich in such peptides. Ganz's research is focused on three families of mammalian antibiotics: defensins, "cathelin-related" peptides, and hepcidins. Ganz and his colleagues are studying their structure, activity, and distribution in cells and tissues; the functions of propeptides in biosynthesis and subcellular targeting; the regulation of antibiotic peptide biosynthesis by developmental, tissue-specific, and microbial signals; and the roles of antibiotic peptides in host defense and inflammation.
More recently, a major focus of the laboratory has been the role of hepcidin in the regulation of iron transport processes. Experimental approaches range from analysis of gene regulation in cell lines and transgenic mice and recombinant production and antimicrobial testing of natural and modified peptides, to histopathologic studies and assays of samples from human patients and experimental animals. Potential applications include the development of novel antibiotic medications, the production of transgenic animals with increased disease resistance, and the development of new treatments for anemia of inflammation and hemochromatosis.
De Domenico I, Ward DM, Langelier C, Vaughn MB, Nemeth E, Sundquist WI, Ganz T, Musci G, Kaplan J. The Molecular Mechanism of Hepcidin-mediated Ferroportin Down-Regulation. Mol Biol Cell. 2007.
Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007; 18(2): 394-400.
Lin L, Valore EV, Nemeth E, Goodnough JB, Gabayan V, Ganz T. Iron-transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4. Blood. 2007.
Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, Nemeth E. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. 2007; 92(5): 583-8.
Tan BH, Meinken C, Bastian M, Bruns H, Legaspi A, Ochoa MT, Krutzik SR, Bloom BR, Ganz T, Modlin RL, Stenger S. Macrophages acquire neutrophil granules for antimicrobial activity against intracellular pathogens. J Immunol. 2006; 177(3): 1864-71.