FAST MOVING FRONTS - 2008

Why do you think your paper is highly cited?

The study of antimicrobial peptides and their role in innate immunity generated a lot of excitement because it focused on how microbes are killed or prevented from multiplying. When the review was written, immunology was still focused predominantly on antigenic recognition, which is only a small part of host defense, and is lacking in invertebrates altogether. The review summarized a lot of ideas that were brewing in the antimicrobial peptide field at the time. I tried to assess objectively and sometimes critically where the field was going, and this may have contributed to the success of this review.

Does it describe a new discovery, methodology, or synthesis of knowledge?

The review is a synthesis of work done by many investigators in the field.

Would you summarize the significance of your paper in layman's terms?

Humans, animals, and plants resist infections by making substances that directly kill germs. These antimicrobials function in many respects like antibiotics and disinfectants sold in a drugstore. This review summarized what was known about one kind of such microbe-killing substances.

How did you become involved in this research and were there any particular problems encountered along the way?

I was lucky to work in the laboratory of Prof. Robert Lehrer, who was a pioneer in the field of antimicrobial peptides. Michael Selsted and I were post-docs there together. I learned biology from Bob Lehrer and peptide technology and chemistry from Mike Selsted. We worked first synergistically and later independently. Our main problem was that it took a few years to convince the immunology community of the importance of this area.

Where do you see your research leading in the future?

While studying urinary defensins, my lab discovered hepcidin, an important peptide that turned out to be the long-sought iron-regulatory hormone. Hepcidin controls the dietary absorption of iron, and regulates its storage and distribution to tissues. Although hepcidin is also involved in innate immunity, we think that it acts predominantly by starving bacteria of iron. I have greatly enjoyed starting from scratch in a new area of biomedicine.

Do you foresee any social or political implications for your research?

Microbes are becoming resistant to existing antibiotics, but the pharmaceutical pipeline for new antibiotics may not be keeping up. I hope that some of the ideas developed through the study of defensins and other antimicrobial peptides will lead to new antibiotics for the treatment of resistant infections or to ways of stimulating natural host defenses to combat infections.

Tomas Ganz, Ph.D., M.D.
Professor of Medicine and Pathology
Department of Medicine
David Geffen School of Medicine at UCLA
Los Angeles, CA, USA

Keywords: antimicrobial peptides, innate immunity, antigenic recognition, host defense, antimicrobials, microbe-killing substances, urinary defensins, hepcidin, pharmaceutical pipeline.