Dr. Karakousis’ primary research interest is the molecular basis of Mycobacterium tuberculosis latency and reactivation. Secondary interests include preclinical screening of novel TB drugs and drug combinations in animal models of caseous necrosis, as well as development of novel molecular assays for the rapid diagnosis of latent TB infection and active TB disease, and for the detection of drug resistance.
The primary focus of the Karakousis Lab is to understand the molecular basis of Mycobacterium tuberculosis latency and reactivation.
Major research activities include studying the adaptation of M. tuberculosis to stress conditions believed to be important in the infected human host, as well as the phenomenon of phenotypic tolerance to antibiotics. In particular, the regulatory cascade involved in the mycobacterial stringent response is under active investigation. A systems biology-based approach is being used to identify host cytokine networks responsible for immunological control of M. tuberculosis growth, as well as M. tuberculosis regulatory and metabolic pathways required for bacillary growth restriction and reactivation.
The laboratory is also actively involved in preclinical drug screening in physiologically relevant animal models.
A third focus of the laboratory is the development of novel molecular assays for the rapid diagnosis of latent TB infection and active TB disease, and for the detection of drug resistance. Specifically, molecular assays using blood, sputum, and urine samples are being investigated with the goal of developing rapid, sensitive and specific point-of-care tests for TB diagnosis and detection of drug resistance.
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Levine DM, Dutta NK, Eckels J, Scanga C, Stein C, Mehra S, Kaushal D, Karakousis PC, Salamon H. "A tuberculosis ontology for host systems biology." Tuberculosis. 2015;95(5):570-574.
Subbian S, Tsenova L, Kim M-J, Wainwright HC, Visser A, Bandyopadhyay N, Bader JS, Karakousis PC, Murrmann GB, Bekker LG, et al. "Lesion-specific immune response in granulomas of patients with pulmonary tuberculosis: A pilot study." PLoS ONE. 2015;10(7).
Xu Z, Zhou A, Ni J, Zhang Q, Wang Y, Lu J, Wu W, Karakousis PC, Lu S, Yao Y. "Differential expression of miRNAs and their relation to active tuberculosis." Tuberculosis. 2015;95(4):395-403.
Zhou A, Ni J, Xu Z, Wang Y, Zhang H, Wu W, Lu S, Karakousis PC, Yao Y-F. "Metabolomics specificity of tuberculosis plasma revealed by 1(H) NMR spectroscopy." Tuberculosis. 2015;95(3):294-302.
Chuang Y-M, Bandyopadhyay N, Rifat D, Rubin H, Bader JS, Karakousis PC. "Deficiency of the novel exopolyphosphatase Rv1026/PPX2 leads to metabolic downshift and altered cell wall permeability in Mycobacterium tuberculosis." mBio. 2015;6(2).