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Lee Klinkenberg, PhD
Research Associate, Division of Infectious Diseases
I am working on several different projects in the lab. The first is the study of the essentiality of M. tuberculosis genes which are upregulated during hypoxia. I am exploring the possibility that these proteins may function as drug targets with the potential for increased potency against persistent bacteria. This study is focused on a set of genes which have been interrupted by the himar1 transposon, and have been found to be attenuated in models of infection which include hypoxia.
The second project focuses on the importance of the RelA protein in tuberculosis infection. This protein and pathway present a novel drug target, which is not expected to share resistance mechanisms with other existing drugs and may even shorten the duration of therapy.
Diagnosis of tuberculosis infection is still a time consuming and expensive process in most of the world. We are developing a point of care diagnostic device which has the potential to diagnose tuberculosis infection in a matter of minutes at a very low cost. This will allow a substantial shortening of the time between presentation and treatment. I am exploring the possible use of transrenal DNA as a biomarker for diagnosis.
To read some of these publications online, click here. Please note that to read the full text of some of these articles requires that you have an online subscription to the journal.
1. Mennella, TA, LG Klinkenberg, and RS Zitomer. 2003. Recruitment of Tup1-Ssn6 by yeast hypoxic genes and chromatin-independent exclusion of TATA binding protein. Eukaryot Cell 2:1288-303. PMID: 14665463
2. Klinkenberg, LG, TA Mennella, K Luetkenhaus, and RS Zitomer. 2005. Combinatorial repression of the hypoxic genes of Saccharomyces cerevisiae by DNA binding proteins Rox1 and Mot3. Eukaryot Cell 4:649-60. PMID: 15821125
3. Klinkenberg, LG, T Webb, and RS Zitomer. 2006. Synergy among differentially regulated repressors of the ribonucleotide diphosphate reductase genes of Saccharomyces cerevisiae. Eukaryot Cell 5:1007-17. PMID: 16835445
4. Jain, SK, SM Hernandez-Abanto, QJ Cheng, P Singh, LH Ly, LG Klinkenberg, NE Morrison, PJ Converse, E Nuermberger, J Grosset, DN McMurray, PC Karakousis, G Lamichhane, and WR Bishai. 2007. Accelerated detection of Mycobacterium tuberculosis genes essential for bacterial survival in guinea pigs, compared with mice. J Infect Dis 195:1634-42. PMID: 17471433
5. Klinkenberg, LG, LA Sutherland, WR Bishai, and PC Karakousis. 2008. Metronidazole lacks activity against Mycobacterium tuberculosis in an in vivo hypoxic granuloma model of latency. J Infect Dis 198:275-83. PMID: 18491971
6. Converse, PJ, PC Karakousis, LG Klinkenberg, AK Kesavan, LH Ly, SS Allen, JH Grosset, SK Jain, G Lamichhane, YC Manabe, DN McMurray, EL Nuermberger, and WR Bishai. 2009. Role of the dosR-dosS two-component regulatory system in Mycobacterium tuberculosis virulence in three animal models. Infect Immun 77:1230-7. PMID: 19103767
7. Ahmad Z, LG Klinkenberg, ML Pinn, MM Fraig, CA Peloquin, WR Bishai, EL Nuermberger, J Grosset, PC Karakousis. Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drug-resistant Mycobacterium tuberculosis in the guinea pig. J Infect Dis 200:1136-43. PMID: 19686043
8. Converse PJ, KD Eisenach, SA Theus, EL Nuermberger, S Tyagi, LH Ly, DE Geiman, H Guo, ST Nolan, NC Akar, LG Klinkenberg, R Gupta, S Lun, PC Karakousis, G Lamichhane, DN McMurray, JH Grosset, WR Bishai. The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models. PLoS One 5:e10289. PMID: 20422019
9. Klinkenberg, LG, J-H Lee, WR Bishai, and PC Karakousis. The stringent response is required for full virulence on Mycobacterium tuberculosis in guinea pigs. J Infect Dis 202:1397-404. PMID: 2949470
10. Be, NA, LG Klinkenberg, WR Bishai, PC Karakousis, SK Jain. Strain-dependent CNS dissemination in guinea pigs after Mycobacterium tuberculosis aerosol challenge. Tuberculosis 91:386-9. PMID: 3172348