My group is interested in the general area of cellular stress responses and the role of molecular chaperones and proteases in these responses. To this end, we utilize various structural, biophysical, biochemical, proteomic, and cell biological approaches to understand the mechanism of function of molecular chaperones and proteases. We are also interested in the development of novel antibiotics by identifying compounds that target these chaperones and proteases and result in the deregulation of protein homeostasis in the cell leading to bacterial cell death.

Key publications:

1. Wong, K. S., Mabanglo, M. F., Seraphim, T. V., Mollica, A., Mao, Y.-Q., Rizzolo, K., Leung, E., Moutaoufik, M. T., Hoell, L., Phanse, S., Goodreid, J., Barbosa, L. R. S., Ramos, C. H. I., Babu, M., Mennella, V., Batey, R. A., Schimmer A. D., & Houry, W. A. “Acyldepsipeptide Analogs Dysregulate Human Mitochondrial ClpP Protease Activity and Cause Apoptotic Cell Death” Cell Chemical Biology accepted (2018).
2. Bhandari, V., Wong, K. S., Zhou, J. L., Mabanglo, M. F., Batey, R. A., & Houry, W. A. “The Role of ClpP Protease in Bacterial Pathogenesis and Human Diseases” ACS Chemical Biology 13(6), 1413−1425 (2018).
3. Chan, S. W. S., Yau, J., Ing, C., Liu, K., Farber, P., Won, A., Bhandari, V., Kara-Yacoubian, N., Seraphim, T. V., Chakrabarti, N., Kay, L. E., Yip, C. M., Pomès, R., Sharpe, S., & Houry, W. A. “Mechanism of Amyloidogenesis of a Bacterial AAA+ Chaperone” Structure 24(7), 1095–1109 (2016).
4. El Bakkouri, M., Rathore, S., Calmettes, C., Wernimont, A. K., Liu, K., Sinha, D., Asad, M., Jung, P., Hui, R., Mohmmed, A., & Houry, W. A. “Structural Insights into the Inactive Subunit of the Apicoplast-Localized Caseinolytic Protease Complex of Plasmodium falciparum” The Journal of Biological Chemistry 288(2), 1022-1031 (2013).
5. Leung, E., Datti, A., Cossette, M., Goodreid, J., McCaw, S. E., Mah, M., Nakhamchik, A., Ogata, K., El Bakkouri, M., Cheng, Y.-Q., Wodak, S. J., Eger, B. T., Pai, E. F., Liu, J., Gray-Owen, S., Batey, R. A., & Houry, W. A. “Activators of Cylindrical Proteases as Antimicrobials: Identification and Development of Novel Small Molecule Activators of the ClpP Protease” Chemistry & Biology 18(9), 1167–1178 (2011).