College: College of Medicine
Department: Division of Infectious Diseases and Global Medicine, Department of Medicine
Curriculum Vitae: PDF
Research Interests: Tuberculosis, Mycobacterial pathogenesis, Regulation of Gene Expression, Vaccines
Hobbies: Reading, gardening, travel
Dr. Josephine Clark-Curtiss has over 30 years of experience conducting research on mycobacteria, and joins the Emerging Pathogens Institute from Arizona State University, where she was a professor in the university’s School of Life Sciences.
After receiving her PhD in microbiology from the Medical College of Georgia, she served initially as a postdoctoral researcher and continued as a research faculty member at the University of Alabama in Birmingham – then the premier medical college in Alabama. She was a faculty member for more than 20 years at Washington University in St. Louis before moving to Arizona State University in 2005.
Through her tuberculosis research, Clark-Curtiss aims to mitigate the spread of one of the world’s most virulent diseases.
“Tuberculosis has been a scourge to humankind since prehistoric times,” she said, “and it remains a serious and significant infectious disease to this day.”
The World Health Organization estimates that one-third of the world’s population is infected by Mycobacterium tuberculosis, the causative agent of TB, with 9.6 million new cases diagnosed in 2014. Not all individuals who are infected develop disease, yet among those who do more than 1.4 million die each year, making TB the most deadly disease caused by a single bacterial pathogen.
Currently, the Clark-Curtiss research group has two primary research interests:
- Understanding mechanisms of tuberculosis pathogenesis through (a) analyses of M. tuberculosis gene expression, (b) identification of operational metabolic pathways during growth of the bacilli in human macrophages and dendritic cells and (c) analyses of regulation of gene expression.
- Development of an effective vaccine against tuberculosis using recombinant attenuated Salmonella vaccine delivery systems producing M. tuberculosis antigens.
To address the first research focus, the team identified M. tuberculosis genes that are expressed at different times after infection of cultured human macrophages, enabling them to identify metabolic pathways that are functional at those times. They have also characterized several classes of regulatory systems that control gene expression, both in vivo and in vitro. These include two-component regulatory systems, serine-threonine protein kinases, and toxin-anti-toxin regulatory modules.
Clark-Curtiss’ interests in developing a tuberculosis vaccine stem from the belief that immunization to protect individuals from infection is superior to the continued development of new antibiotics to combat bacterial pathogens that inevitably acquire resistance to currently available or newly designed antibiotics. Her research group is using recombinant attenuated Salmonella vectors as vaccines (RASVs) to deliver M. tuberculosis antigens to elicit protective immune responses. The group uses RASVs because (a) Salmonella can elicit mucosal, antibody, and cell-mediated immune responses in immunized individuals, (b) much is known about the genetics and physiology of Salmonella, which enables researchers to rationally design RASVs that are completely attenuated, but can target specific organs, cells and cellular compartments to enhance immune responses, and (c) RASVs can be delivered orally, thereby precluding the use of needles or need for refrigeration for transportation of the vaccines to remote geographic locations.
Emerging Pathogens Institute
2055 Mowry Rd.
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Office: Rm 258
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