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Petros
C.
Karakousis
,
MD

Professor

Contact Info

Center for Tuberculosis Research, 1550 Orleans Street, Room 110
Baltimore
Maryland
21287
US        
410-614-8173

Research Interests

Tuberculosis; HIV; Latent infection; Persistence; Host-pathogen interactions; Host-directed therapy; Vaccines; Biomarkers
Experiences & Accomplishments
Education
MD
Washington University School of Medicine
1998
Overview
The primary focus of the Karakousis Lab is to understand the molecular basis of persistence and reactivation in Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). 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 defense mechanisms responsible for immunological control of M. tuberculosis growth, as well as M. tuberculosis regulatory and metabolic pathways required for bacterial persistence and antibiotic tolerance.
The laboratory is also actively investigating the repurposing of various clinically available agents with immune-modulatory properties as adjunctive host-directed therapy, in order to shorten the duration of TB treatment and improve lung pathology. A randomized clinical trial of Statins as Adjunctive Therapy for TB (StAT-TB trial) is investigating the potential adjunctive role of pravastatin in improving microbiological and lung-function outcomes in HIV-infected and uninfected individuals with drug-susceptible, pulmonary TB in South Africa.
Finally, 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.
Honors & Awards
1992 Ford Foundation Scholarship
1993 National Science Foundation Scholarship
1994 Phi Beta Kappa, Johns Hopkins University
1990-1994 Dean's List, summa cum laude, Johns Hopkins University
1994-8 Distinguished Alumni Scholarship (full-tuition academic scholarship at
Washington University School of Medicine)
1995 Antoinette Frances Dames Prize in Cell Biology and Physiology, Washington
University School of Medicine, St. Louis
1997 Hellenic Medical Student Scholarship, Hellenic Medical Society of New York
1998 Missouri State Medical Association Award
1998 Alpha Omega Alpha, Washington University School of Medicine
2000 Maurice F. Attie Resident Teaching Award, Univ. of Pennsylvania, Dept. of Medicine
2001 Edward W. Holmes Resident Research Award, Univ. of Pennsylvania, Dept. of Medicine
2004 Best abstract, Assembly of Microbiology, Tuberculosis, and Pulmonary Infections, American
Thoracic Society (ATS) annual meeting
2005 Arthur M. Dannenberg, Jr. Award for Postdoctoral Research, JHU School of Medicine
2009 Basic Research Junior Faculty Award, JHUSOM Dept. of Medicine
2010 Fellow, Infectious Diseases Society of America
Select Publications
Selected publications from the last 5 years:
  • Lanzas F, Ioerger TR, Shah H, Acosta W, Karakousis PC. First evaluation of GenoType MTBDRPlus 2.0 performed directly on respiratory specimens in Central America. J Clin Microbiol. 2016; 54:2498-502. PMCID: PMC5035431.
  • Aggarwal A, Parai MK, Shetty N, Wallis D, Woolhiser L, Hastings C, Dutta NK, Galaviz S, Dhakal RC, Shrestha, R, Wakabayashi S, Walpole C, Matthews D, Floyd D, Scullion P, Riley J, Epemolu O, Norval S, Snavely T, Robertson GT, Rubin EJ, Ioerger TR, Sirgel EA, van der Merwe R, van Helden PD, Keller P, Böttger EC, Karakousis PC, Lenaerts A.J, Sacchettini JC. Development of a novel lead that targets M. tuberculosis polyketide synthase 13. Cell. 2017;170:249-259. PMCID: PMC5509550.
  • Degner NR, Wang J-Y, Golub JE, Karakousis PC. Metformin use reverses the increased mortality associated with diabetes mellitus during tuberculosis treatment. Clin Infect Dis. 2018;66:198-205. PMCID: PMC5848303.
  • Dutta NK, Klinkenberg LG, Vazquez MJ, Segura D, Colmenarejo G, Ramon F, Rodriguez B, Mata LC, Porras ED, Chuang Y-C, Rubin H, Lee J-J. Eoh H, Bader J, Perez E, Mendoza A, Karakousis PC. Inhibiting the stringent response blocks Mycobacterium tuberculosis entry into quiescence and reduces persistence. Sci Adv. 2019;5:eaav2104. PMCID: PMC6426458.
  • Dutta NK, Bruiners N, Zimmerman MD, Tan S, Dartois V, Gennaro ML, Karakousis PC. Adjunctive host-directed therapy with statins improves tuberculosis-related outcomes in mice. (In press, J Infect Dis.).
Projects
Biomarkers of TB progression and response to therapy
Statins as Adjunctive Therapy for Tuberculosis (StAT-TB)