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Interview with Journal of Cell Death editorial board member Dr Hardy Kornfeld

Posted Fri, Jun, 04,2010

This interview is with Journal of Cell Death editorial board member Dr Hardy Kornfeld. Journal of Cell Death is an open access journal published by Libertas Academica.

Editor in Chief Dr Garry Walsh has recently issued a call for papers

What is the primary focus of your research?


My lab studies host defense against respiratory infections with a heavy emphasis of tuberculosis. Within the general area we focus on infection-induced cell death and its contribution to TB pathogenesis, the impact of diabetes and dyslipidemia on protective immunity against Mycobacterium tuberculosis and Klebsiella pneumoniae, and on the development of novel therapeutics and vaccines.

What are the most exciting developments arising from current research in your area?

We previously discovered that macrophages infected with M. tuberculosis can undergo TNF-dependent, caspase-mediated apoptosis. This appears to serve a protective function for the host similar to apoptosis in response to virus infections. Virulent M. tuberculosis strains are capable of inhibiting this apoptosis, similar to the anti-apoptotic capacity of certain viral pathogens.

More recently we turned our attention to learn how virulent bacilli exit the macrophage. We discovered that although these strains initially preserve host cell viability, after growing to a threshold intracellular burden they trigger a unique macrophage cell death mode with features of apoptosis and necrosis. This death, which liberates the bacilli for spreading infection, is caspase-independent and has distinct characteristics that are different from apoptosis, pyroptosis or pyronecrosis.

Who are your main collaborators? Please describe your work with them

Christopher Sassetti (UMass Medical School): Dr. Sassetti is an expert in mycobacterial genetics and we collaborate on studies seeking to identify M. tuberculosis genes that mediate macrophage cytolysis.

Heinz Remold (Brigham & Women's Hospital): Our original interest and earliest investigations of TNF-mediated macrophage apoptosis arose as a collaboration with Dr. Remold. We continue to collaborate with him in various aspects of the infection-induced cell death project.

How did you come to be working in your research area?

After completing clinical/research fellowships in infectious diseases (St. Luke's-Roosevelt Hospital) and pulmonary medicine (Boston University Medical Center) I completed a postdoctoral fellowship in molecular virology with Dr. James Mullins when he was at the Harvard School of Public Health. My first paper (from ID fellowship) was a clinical investigation of persons at risk for the disease called GRID that was later named AIDS, and in Dr. Mullins' lab I isolated the first biologically active clone of simian immunodeficiency virus. When I established my own lab the original focus was on AIDS-related pulmonary infections, particularly cryptococcosis. Later I began to study TB in this context but became fascinated by the pathobiology of TB and the role of macrophage cell death in this disease in the absence of HIV infection.

What do you think about the development of open access publishing? Have you published in an open access journal? What motivated you to do so?

Open access publishing is the way of the future and will surely accelerate the expansion of scientific knowledge. My own research is supported entirely by public funding and I consider it a fiduciary responsibility to disseminate any new knowledge arising from this work without restriction.

What articles and/or books have you published recently?

Martens et al. Hypercholesterolemia impairs immunity to tuberculosis. Infect. Immun. 2008; 76:3464.

Gan et al. Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence. Nature Immunol. 2008; 9:1189.

Friedline et al. In vivo trans-regulation of CLTA-4 deficient T cells requires CTLA-4 expressing CD4+CD25+ regulatory T cells. J. Exp. Med. 2009; 206:421.

Mathurin et al. CD4 T cell-mediated heterologous immunity between mycobacteria and poxviruses. J. Virol. 2009; 83:3528.

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