Select a year 2001 2002 2003    Select a researcher Alan G. Barbour, M.D. William Bishai, M.D., Ph.D. Martin J. Blaser, M.D. John C. Boothroyd, Ph.D. Jon Clardy, Ph.D. Peter Cresswell, Ph.D. Roy Curtiss, III, Ph.D. Ronald W. Davis, Ph.D. Jack E. Dixon, Ph.D. Stanley Falkow, Ph.D. Gerald R. Fink, Ph.D. Richard A. Flavell, Ph.D. Lee Gehrke, Ph.D. Laurie H. Glimcher, M.D. Jeffrey I Gordon, M.D. Daniel L. Hartl, Ph.D. William R. Jacobs, Jr., Ph.D. Keith A. Joiner, M.D., co-PI Karla Kirkegaard, Ph.D. Roberto G. Kolter, Ph.D. W. Ian Lipkin, M.D. Richard M. Locksley, M.D. Carl Nathan, M.D. Peter Palese, Ph.D. Pradipsinh K. Rathod, Ph.D. David A. Relman, M.D. Charles M. Rice, Ph.D. Alexander Rich, M.D. Lee W. Riley, M.D. David S. Roos, Ph.D. Abigail A. Salyers, Ph.D. Gary K. Schoolnik, M.D. Iwona Stroynowski, Ph.D. Ronald P. Taylor, Ph.D. Elisabetta Ullu, Ph.D. John Waitumbi, D.V.M., Ph.D Select a project A Gnotobiotic Zebrafish Model for Analyzing Symbiotic Host...Antiviral Effects of Interferon-Inducible Cytosolic ProteinsArming the Immune System against Pathogens with Selective ...Bacterial Pathogen Families that Function in Both the Anim...Cellular Genes and Viruses: Who Wins The War?Conditional Targeted Deletions in Plasmodium falciparum...Designing and Mining Pathogen Genome Databases: The Apicop...Development of Genetic Systems for Genetically Intractable...Development of New Genetic Tools to Identify Nutrient Upta...Ecological Influences on Pathogen Genome EvolutionEvolution of Virulence in Eukaryotic PathogensExploiting an Evolutionary Omission in Pathogenic RNA Viru...Exploring Novel Pathways of Immune Defenses Against Orally...Genomic Approach to Improved Immunogenicity of M. tuber...Genomic tools to characterize hypermutating Plasmodium fal...Investigation of Mechanisms Leading to Anemia at Low Paras...Molecular definition of the bacterial population of human ...Mycobacterium Tuberculosis Latency and Reactivation Tuberc...New Antibiotics from Environmental DNAOptimizing Immunity to Complex Pathogens In VivoPandora's Box ProjectProviding an Economic Benefit to Using a Vaccine to Enhanc...Resistance Gene Flow in the Human Colonic MicrofloraRole of Nucleotide Binding Domain-Leucine Rich Repeat Prot...Sexually Transmitted Disease Agents in the “Healthy” Human...Systematic Analysis of Positive-strand RNA Viral Transmiss...The Human Intestinal Microbiome: Community Analysis, Host ...The Molecular Ecology of Vibrio cholerae in the Gangetic D...The Natural History of Typhoid Infection in VietnamThe Role of Quorum Sensing in Fungal DiseaseTowards Broad-spectrum Antivirals: Functional Screens for ...Transmission Blocking Vaccines for TuberculosisTransmission-blocking Vaccines Against Arthropod VectorsViral Pathogenic Mechanisms Involving Z-DNA Binding Proteins Select an institution Albert Einstein College of Medicine of Yeshiva University Columbia University Harvard Medical School Harvard School of Public Health Harvard University Johns Hopkins School of Public Health Massachusetts Institute of Technology Mount Sinai School of Medicine New York University School of Medicine Rockefeller University Stanford University School of Medicine Stanford University School of Medicine, VA Palo Alto Health Care System University of California - Berkeley University of California - Irvine University of California - San Diego University of California - San Francisco University of Illinois - Urbana-Champaign University of Pennsylvania University of Texas Southwest Medical Center University of Virginia University of Washington Washington University Washington University School of Medicine Weill Medical College of Cornell University Whitehead Institute for Biomedical Research Yale University School of Medicine

William Bishai, M.D., Ph.D. Johns Hopkins School of Public Health

Mycobacterium tuberculosis is an obligate human pathogen whose only significant reservoir is the human host. Of the 6 billion world inhabitants, 2 billion are infected with latentM. tb. and approximately 8 million have active, transmissible tuberculosis. A strategy to block transmission from the 8 million active cases to the 4 billion susceptible individuals would, over time, lead to the elimination of TB.

The ultimate goal of this research is to develop transmission-blocking vaccines against TB. Such vaccines would prevent the evolution of transmissible TB among vaccinees. It is estimated that an average active case of TB leads to 8 - 10 new infections. Even if the vaccine did not block disease, but kept recipients non-infectious, the ability to interrupt TB spread would be of significant public health value.

The full cycle of TB transmission requires bronchial rupture of virulent M. tb and exhalation of the microbe into the environment for subsequent inhalation by a susceptible host. While patients who lack cavitary TB are capable of transmitting the disease, it has been well documented that patients with large cavitary lesions or with laryngeal TB are the most productive disease transmitters. The goal of this project is to illuminate the poorly understood phenomenon of cavity formation, to identify both bacterial and human determinants of cavitation, and to develop rational vaccines to inhibit transmission by preventing cavitary disease.

The project will rely heavily upon the rabbit TB model. In contrast to in vitro models and other animal models of TB, the rabbit is unique in forming both liquefied and cavitary TB granulomas and in exhaling infectious aerosols (Table 1). These features closely mimic human TB.

Table 1

Site of Bacteria or Stage	In vitro Macrophage Model	Mouse Model	Guinea Pig Model	Rabbit Model
Inhalation		+	+	+
Alveolar granuloma	+	+	+	+
Immature granuloma *		+	+	+
Solid caseous granuloma		+	+	+
Liquefied granuloma				+
Cavitary granuloma				+
Bronchial rupture				+
Exhalation / Transmission				+

*multinucleated giant cells, foamy macrophages, peripheral mononuclear cells

Using the rabbit model of tuberculosis we will correlate infectivity with pulmonary disease stage, identify bacterial and host factors which control and modulate cavity formation, and evaluate interventions to block cavitation and disease transmission.

Contact Dr. Bishai.