Targeted Pathogens

The Keck Center targets the microbial pathogens Pseudomonas aeruginosa (the major cause of morbidity and death in cystic fibrosis) and three groups of pathogenic protozoa that cause untold suffering in the developing world (Trypanosomes, Leishmania, and the malarial Plasmodium).

Pseudomonas

P. aeruginosa is a major cause of opportunistic infections, not only in Cystic fibrosis (CF), but also in burn victims, cancer patients, and others whose defenses against infection are compromised. P. aeruginosa is a complex Gram-negative bacterium that can acquire increased, host-specific virulence through genetic alterations. P. aeruginosa can also serve as a prototype for other major bacterial pathogens, such as Salmonella and Yersinia species, Gram-negative bacteria that causes substantial morbidity and mortality worldwide, and which share with P. aeruginosa the ability to adapt to the unique environment of the human host. (Click on image to visit Pseudomonas Genome Project.)

Cystic Fibrosis Research

The University of Washington is a leader in clinical CF research and in the study of the molecular pathogenesis of P. aeruginosa infection in CF. Indeed, the complete sequence of the P. aeruginosa genome was generated by Keck Center investigators and our colleagues, as were the first comprehensive DNA microarrays and proteomic approaches to study P. aeruginosa. Our work in this area is also supported by the Cystic Fibrosis Foundation and NIH.

CF is a multisystem disease caused by mutations that affect expression of the cystic fibrosis transmembrane conductance regulator protein (CFTR). For reasons that are not understood, loss of CFTR function causes a predisposition to P. aeruginosa infection, leading to progressive, unremitting, and ultimately fatal inflammation of the airspaces in the lung. Airway inflammation develops during infancy, increases slowly, and cannot be fully reversed by any current forms of intervention.

Pathogenic Protozoa

The diseases caused by pathogenic protozoa — malignant malaria by Plasmodium falciparum, African sleeping sickness by Trypanosoma brucei, Chagas’ disease by Trypanosoma cruzi, and cutaneous and disseminated Leishmaniasis by Leishmania spp.— afflict hundreds of millions of people each year, causing debility, disfigurement, and death primarily in the developing world. The quality of life in much of the developing world will not improve significantly until the human, social, and economic burden of these diseases is lifted. Keck Center investigators have played a notable role in studies to elucidate the biology of these pathogens and to identify new targets for drugs to prevent or treat these infections. This effort also enjoys strong support from the NIH, including a newly funded program in structural genomics.

Microbial pathogens easily spread within and between countries, and have the potential to evolve resistance to our treatments or vaccines faster than we can devise new ways to combat them. To regain momentum in this arms race between humans and microbes, we have created this interdisciplinary Center linking the considerable strengths of the University of Washington in functional, structural, and chemical genomics with microbial pathogenesis and immunology. We hope our Keck Center will serve as a model for collaborative, high technology approaches to infectious diseases and other fundamental medical problems at this University and elsewhere.

We have begun to recruit new faculty to strengthen key areas of our consortium and to acquire additional state-of-the-art resources needed to meet our gorals. We have also assembled a steering committee and an advisory board, initiated a regular seminar series alternating between presentations of research-in-progress by Center investigators and presentations of cutting edge work by outside experts to encourage strong collaborations and the development of new technologies.