University of Maryland School of Medicine: 1978 (Assistant); 1983 (Associate); 1990 (Professor).
I have over thirty years of experience studying microbial pathogenesis and the hosts' responses to infections. As a graduate student at Johns Hopkins, my research was focused on the biology and ecology of a hepatic nematode, Capillaria hepatica parasitism in the commensal rat, Rattus norvegicus. Developmentally arrested C. hepatica eggs are deposited and trapped in the host's liver and the death of the host either by being eaten or dying and decomposing is required for completion of the parasite life cycle. My work identified the biological attributes of exit mechanisms by which C. hepatica perpetuate in nature. Since 1980s, the focus of my laboratory research was to decipher the molecular and cellular basis by which rickettsiae invade eukaryotic host cells and evade ensuing host immune responses. My long-term NIAID funded projects addresses the mechanisms by which arthropod innate immune responses are activated against colonizing intracytoplasmic rickettsiae. Our research on the identification of molecules associated with rickettsial infection resulted in the characterization of several tick immune-responsive molecules including Factor D, lyzozymes, ferritin HC, histamine binding and release factors, two novel glutathione S-transferases, a kunitz-type serine protease inhibitor Dv-KPI and defensins. Furthermore, our interest in rickettsial secreted proteins have resulted in the characterization and functional analysis of R. typhi surface cell antigens, phospholipases, and Rickettsia ANK( RARP). Because of my expertise in vector-borne pathogens, I served as a member of the committee that independently reviewed the IOM workshop report on the "Critical Needs and Gaps in Understanding Prevention, Amelioration, and Resolution of Lyme and other Tick-borne Diseases". The report clearly provides strong case for follow up studies on arthropod-borne pathogens and in particular little known rickettsial diseases. Proudly speaking, over the past 28 years of my funded grants, we have made major breakthroughs in the field of rickettsial biology, trained 12 Ph.Ds and over thirty postdoctoral fellows. The continuation of our ongoing research will further advance understanding of the cell and molecular biology of rickettsiae and their interactions with their arthropod and mammalian hosts.
Grants & Contracts:
NIH/NIAID, R01 AI 17828, Murine Typhus: Vector Biology and Transmission, 09/01/1982 through 06/29/2013. The goal of this project is to determine the degree of interplay between the Rickettsia typhi in fleas and mammalian hosts. The proposed experiments aim at elucidating the mechanism of rickettsial entry and growth in the flea gut epithelial lining and mammalian cell lines and to identify, clone and characterize genes encoding R. typhi virulence-associated proteins.
NIH/NIAID, 3R01AI017828-27S1, Murine Typhus: Vector Biology and Transmission 09/29/2013- Supplement to parent grant.
NIH/NIAID, R01 AI 43006, Interspecific Competition Between Rickettsiae in Ticks, 03/01/98 through 06/30/15. This proposal specifically addresses transovarial interference of the human pathogen, Rickettsia rickettsii, in the tick vector transovarially infected with nonpathogenic rickettsiae.
Completed Reseach Support:
NIH/NIAID, R01AI059118, Generation of Genetically Attenuated Rickettsiae, 04/15/05 to 01/31/11. This proposal focuses on generation of Rickettsia prowazekii and R. rickettsii mutants lacking functional virulence genes. These attenuated non-virulent mutants then would be used to develop broad-based protective rickettsial vaccines.
NIH/NIAID, R56 AI063534-01A1, Rickettsia felis & other emerging rickettsial pathogens. 08/01/06 to 07/31/07. The overall goal of this grant is to delineate the various aspects of the R. felis life cycle to identify biological events critical to rickettsial survival and to determine the role of R. felis genes in infectivity and pathogenesis.
NIH/NIAID, R01 AI 47445, The Biology and Immunology of Malaria Parasite Liver-Stages, 12/01/00 to 11/30/07. The major objectives of our research are to identify Plasmodium yoelii genes in the infected mouse liver, the expression of which is induced early after infection, and shut off during the blood-stage cycle.