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Hwan Kim


Assistant Professor

Department of Microbiology and Immunology
Ph.D., University of Chicago, 2011

E-mail:
Office:
Fax:

Hwan.Kim@stonybrook.edu
(631) 632-
(631) 632-9797

 

Publications


Research

Our laboratory examines the molecular mechanisms whereby pathogenic Rickettsia cause human diseases.

Rickettsia prowazekii is the causative agent of the louse-borne epidemic typhus, bringing pestilential mortality in times of war and famine. During the Napoleonic Wars, typhus affected one-third of the French army (500,000 soldiers) and contributed to their defeat during the Russian and Prussian campaigns. During World Wars I and II, typhus outbreaks among frontier soldiers and in concentration camps claimed millions of lives. In the United States and Europe, along with sporadic cases of endemic typhus (R. typhi), Rocky Mountain Spotted Fever (R. rickettsii) and Boutonneuse Spotted Fever (R. conorii) cases have been reported with fatality ratios of up to 25%, rivaling in impact that of other deadly diseases such as plague and meningococcemia. Of note, there are no licensed vaccines or immune preventive measures against rickettsial infections.

A hallmark of rickettsial diseases is pathogen invasion into vascular endothelial cells followed by intracellular replication. This triggers vascular pathologies and bacteremia that allow transmission of the pathogens into uninfected arthropod vectors. Beyond the pathological description of rickettsial replication and disease, the molecular mechanisms whereby rickettsiae grow and divide, colonize arthropods, promote transovarian and transstadial transmissions among arthropod vectors, invade vertebrate endothelial cells, and spread from cell to cell to cause acute disease or persistent infection with relapse (Brill–Zinsser disease) are poorly understood. 

Deep understanding of Rickettsia pathogenesis requires the large-scale generation of mutations with defined lesions and phenotypic analysis of such mutants. Unfortunately, progress in the identification of essential and virulence genes and their functions has been hampered by the lack of genetic tools. This goal is currently being pursued in our laboratory, where we have developed kkaebi insertional mutagenesis technology to generate a library of R. conorii variants. By characterizing two of the kkaebi variants, we discovered that the polysaccharide synthesis operon is conserved among pathogenic Rickettsia, responsible for O-antigen biosynthesis, contributes to the rickettsial pathogenesis, and is essential for the development of bactericidal Weil-Felix antibodies. Our laboratory engages genetic, biochemical, and microscopic analyses along with animal infection models to identify molecular mechanisms of virulence factors involved in rickettsial pathogenesis. Our research will be useful for the prevention and treatment of human infections caused by pathogenic Rickettsia.