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Josephine Clark-Curtiss is currently a professor of medicine with the Division of Infectious Diseases and Global Medicine, Department of Medicine with the University of Florida.
Dr. Clark-Curtiss initiated her research career during her PhD studies at the Medical College of Georgia, Augusta, Georgia. She then joined the research group of Roy Curtiss III at the University of Alabama at Birmingham for postdoctoral studies, initially analyzing the genetic bases for transfer of antibiotic resistance (R) plasmids among enterobacteria. With the inception of recombinant DNA technology, she became part of the Curtiss research team that constructed and characterized the first biologically contained “safe” strains c1776 and DP50 of Escherichia coli that, for a time, were the only approved bacterial strains with which investigators throughout the U.S. could conduct recombinant DNA research in the late 1970s.
Dr. Clark-Curtiss subsequently utilized recombinant DNA techniques to conduct research on mycobacteria, beginning in the early 1980s, when she and her colleagues constructed the first recombinant DNA libraries of any mycobacterial strain, thereby initiating molecular genetics research on Mycobacterium leprae and later, on M. tuberculosis and M. avium.
Clark-Curtiss and her research group were among the first to identify specific genes that encoded M. leprae proteins and they were the first to demonstrate the presence of a repeated DNA sequence in the chromosome of M. leprae (now known as Rlep, which is used for the diagnosis of leprosy). Using restriction fragment length polymorphism (RFLP) analyses of genomes from M. leprae isolates from all over the world, Dr. Clark-Curtiss showed that the M. leprae genome is remarkably stable genetically. Dr. Clark-Curtiss’ research group was the first to identify genes encoding antigens of M. leprae that were recognized by antibodies in the sera of leprosy patients.
BS, Biology, St. Mary's College, Notre Dame, IN
PhD, Microbiology, Medical College of Georgia, August, GA
Currently, in collaboration with Roy Curtiss III, the Clark-Curtiss group is developing a safe, efficacious vaccine to protect humans against infections by M. tuberculosis, using recombinant, attenuated Salmonella vaccine (RASV) strains to deliver M. tuberculosis protective antigens. The RASV strains are engineered to behave like wild-type Salmonella as they traverse the mammalian gastrointestinal tract after oral inoculation, but then, using regulated delayed technologies, to begin synthesizing the antigens after the RASVs have colonized internal lymphoid tissues.
The RASVs are also engineered to undergo regulated delayed lysis in vivo, to preclude long-term colonization of the immunized host and to release the synthesized antigens into the cytosol of the host cells, to elicit both humoral (antibody) and cell-mediated immune responses. Several of the RASV-M. tuberculosis constructs provide protection in mice against aerosol challenges with virulent M. tuberculosis that is equivalent to or slightly better than that conferred by M. bovis BCG, which is regarded as the gold standard for vaccines against M. tuberculosis.
The Clark-Curtiss research group is continuing to improve the RASV and is also analyzing the protective capabilities of nine other M. tuberculosis antigens for possible incorporation into candidate RASV-M. tuberculosis constructs.