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New and Innovative Approaches to Fighting Tuberculosis

Weill Cornell Medical College

The research group headed by Dr. Carl Nathan, chairman of the Department of Microbiology and Immunology, and R.A. Rees Pritchett Professor of Microbiology at Weill Cornell Medical College, and director of the Abby and Howard P. Milstein Program in Chemical Biology, is heavily involved with efforts to fight tuberculosis. Although this is not the only focus, the group has made and continues to make significant research contributions in this area. Dr. Nathan's laboratory is an interdisciplinary group, with extensive collaborations and regular interactions with other research labs. Dr Nathan has publicly encouraged bold new initiatives to address the crisis of antibiotic resistant bacteria. He supports the creation of not-for-profit drug companies which could focus on identifying and patenting new drugs and new drug combinations overlooked by for-profit pharmaceutical companies. He also advicates changing regulations to encourage new development of medicines against bacterial infection, and to discourage overuse.

Dr. Nathan and his colleagues have helped to shape our basic understanding of innate immunity and host-pathogen interactions. He introduced the concepts of cytokine-mediated activation and deactivation of macrophages, helped identify the first macrophage activating factor (interferon-γ) and its therapeutic potential, demonstrated the role of the respiratory burst in macrophage biology, and pioneered numerous advances in inducible nitric oxide synthase (iNOS), which plays a key role in the immune system. These contributions inform current research efforts, including those directed at macrophage interactions with Mycobacterium tuberculosis.

Dr. Nathan is Director of the Abby and Howard P. Milstein Program in Chemical Biology, which has been established to expedite discovery of new drug treatments; foster unique and innovative collaborations; and bolster the fight against disease, with an initial emphasis on infectious diseases such as malaria and tuberculosis, which are particularly challenging problems in Africa.

Dr. Nathan has recently received a large grant from the Bill & Melinda Gates Foundation. "These grants support research focused on testing many existing chemical compounds for their potential ability to kill or interfere with the organism that causes TB. We already know of and use some compounds that kill or weaken TB pathogens when they are in the replicating phase. Being able to kill TB organisms in their non-replicating phase, which represents most of their existence, will be key to shortening curative TB therapy from the current six months (or longer) to perhaps just a couple of weeks," said Dr. Nathan in a Weill Cornell News Bulletin. "Finding those effective compounds may also mean more effective therapies for the emerging drug-resistant forms of TB."

"These grants will also help us to demonstrate to drug companies a safe way to screen hundreds of thousands of chemical compounds against the TB organism so the companies can do it themselves," says Dr. Nathan. "Right now very few drug companies have the special core facilities needed to do such work without risk of infection."

The group has identified several potential new drug sto fight tuberculosis in the dormant phase. Eliminating the bacteria in its dormant form is a new immunological approach with great potential, which could prevent TB's spread. The group has also received a grant from the Bill & Melinda Gates Foundation to fund study of the genetic mechanism by which tuberculosis emerges from its latent state into an infectious and symptomatic disease.

For additional and up-to-date information, please visit http://www.cornellmicrobiology.org