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Investigators and Program Directors

Kathleen A. McDonough

Research Scientist, Wadsworth Center, Microbial Genetics
Associate Professor, School of Public Health, Biomedical Sciences

Ph.D., Stanford University
Postdoctoral training, Howard Hughes Medical Institute, Albert Einstein College of Medicine

Research Interests

The focus of this laboratory is gene regulation in the context of bacterial pathogenesis, or the means by which bacteria cause disease. We are primarily interested in two well known pathogens: Mycobacterium tuberculosis, the bacterium that causes TB, and Yersinia pestis, the etiologic agent of bubonic and pneumonic plague. We use a variety of techniques in our studies with both pathogens, ranging from molecular genetics and biochemistry to bioinformatics, proteomics and fluorescence microscopy.

M. tuberculosis is an air-borne pathogen that remains one of the world's leading killers. Our goal is to identify the specific genes and properties of virulent TB bacteria that enable it to establish infection and latency. Ultimately, we expect that the products of these genes will be useful targets for vaccine and/ or new anti-TB drug development. Areas of current study include the interaction of tubercle bacilli with host macrophages, with lung epithelial cells and granulomas at the cellular and molecular levels. We're particularly interested in learning how TB bacteria regulate their gene expression in response to these different environments. We have recently discovered that M. tuberculosis makes extensive use of the classic signal transduction molecule, cyclic AMP (cAMP), to regulate its gene expression in host-associated environments. We are also exploring the effects of cAMP secretion on host macrophage functions during infection.

Y. pestis is considered a high risk biological threat agent, a source of natural infection and an ideal candidate for the study of how infectious agents evolve. Little is known about what differentiates Y. pestis from Y pseudotuberculosis, a closely related but less virulent pathogen that cannot be transmitted by fleas. Currently, we are exploring the roles of small regulatory RNAs (sRNA) in plague biology and the genetic differentiation of these two pathogens.

>> Select Publications

Contact Information

E-mail: kathleen.mcdonough@wadsworth.org