Harvard T.H. Chan School of Public Health Department of Immunology and Infectious Diseases
Cambridge, Massachusetts USA
Member since 2018
Representative
Eric Rubin, MD Ph.D. Adjunct Professor of Immunology and Infectious Diseases
Team
- Kristi Guinn
- Harry Won
- Olga Kandror
- Tatos Akopian
About
The Rubin Lab focuses on tuberculosis, including its cell biology, pathogenesis, and interventions that can help treat and prevent disease. We have developed some of the genetic tools that are used to study the causative organism, Mycobacterium tuberculosis (Mtb), and have employed these to understand the molecular mechanisms underlying virulence, and susceptibility and resistance to antibiotics. The lab collaborates widely both within Harvard and with the broader TB research community.
Role & Expertise
Within the TBDA, we are studying Mtb’s Clp protease as a potential new drug target. We are applying and developing both biochemical and cellular assays for the Clp complex and its individual components.
References
- Kester, J. C.; Kandror, O.; Akopian, T.; Chase, M. R.; Zhu, J.; Rubin, E. J.; Goldberg, A. L.; Fortune, S. M. ClpX Is Essential and Activated by Single-Strand DNA Binding Protein in Mycobacteria. Journal of Bacteriology 2021, 203 (4). https://doi.org/10.1128/JB.00608-20.
- Fraga, H.; Rodriguez, B.; Bardera, A.; Cid, C.; Akopian, T.; Kandror, O.; Park, A.; Colmenarejo, G.; Lelievre, J.; Goldberg, A. Development of High Throughput Screening Methods for Inhibitors of ClpC1P1P2 from Mycobacteria Tuberculosis. Analytical Biochemistry 2019, 567, 30–37. https://doi.org/10.1016/j.ab.2018.12.004.
- Li, M.; Kandror, O.; Akopian, T.; Dharkar, P.; Wlodawer, A.; Maurizi, M. R.; Goldberg, A. L. Structure and Functional Properties of the Active Form of the Proteolytic Complex, ClpP1P2, from Mycobacterium Tuberculosis. Journal of Biological Chemistry 2016, 291 (14). https://doi.org/10.1074/jbc.M115.700344.
- Gavrish, E.; Sit, C. S.; Cao, S.; Kandror, O.; Spoering, A.; Peoples, A.; Ling, L.; Fetterman, A.; Hughes, D.; Bissell, A.; Torrey, H.; Akopian, T.; Mueller, A.; Epstein, S.; Goldberg, A.; Clardy, J.; Lewis, K. Lassomycin, a Ribosomally Synthesized Cyclic Peptide, Kills Mycobacterium Tuberculosis by Targeting the ATP-Dependent Protease ClpC1P1P2. Chemistry & Biology 2014, 21 (4), 509–518. https://doi.org/10.1016/j.chembiol.2014.01.014.
- Raju, R. M.; Jedrychowski, M. P.; Wei, J. R.; Pinkham, J. T.; Park, A. S.; O’Brien, K.; Rehren, G.; Schnappinger, D.; Gygi, S. P.; Rubin, E. J. Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium Tuberculosis. PLoS Pathogens 2014, 10 (3). https://doi.org/10.1371/journal.ppat.1003994.
- Raju, R. M.; Unnikrishnan, M.; Rubin, D. H. F.; Krishnamoorthy, V.; Kandror, O.; Akopian, T. N.; Goldberg, A. L.; Rubin, E. J. Mycobacterium Tuberculosis ClpP1 and ClpP2 Function Together in Protein Degradation and Are Required for Viability in Vitro and during Infection. PLoS Pathogens 2012, 8 (2). https://doi.org/10.1371/journal.ppat.1002511.