Walid A. Houry

Walid A. Houry


BSc, American University of Beirut, 1990
MSc, Cornell University, 1991
PhD, Cornell University, 1996
Postdoc, Sloan-Kettering Institute, 1997
Postdoc, Max-Planck-Institute for Biochemistry, 2000

Address 661 University Avenue, MaRS Centre
West Tower, Room 1612
Toronto, ON M5G 1M1
Lab Houry Lab
Lab Phone 416-946-7364
Office Phone 416-946-7141
Email walid.houry@utoronto.ca

Director of the Analytical Ultracentrifugation Facility in the Biochemistry Department, Faculty of Medicine, Medical Science Building, University of Toronto (September, 2004 – current).

Founding member and on the organizing committee of the BiophysTO seminar series, University of Toronto (September, 2015 – current).

Editorial board member of the Journal of Biological Chemistry  (July 1, 2017 – June 30, 2022).

Associate Editor of Frontiers in Protein Folding, Misfolding and Degradation, a section of Frontiers in Molecular Biosciences (January, 2014 – current).

On the Editorial Board of Microbial Cell (January, 2014 – current).

Editor for the Research Topic “The Role of AAA+ Proteins in Protein Repair and Degradation” in Frontiers in Molecular Biosciences (2017).

Editor of the book “Systems Biology & Interactomics: The Molecular Chaperones Interaction Networks in Protein Folding and Degradation”, Springer Science + Business Media (2014).

Editor of The Biomedical & Life Sciences Collection, Henry Stewart Talks Series on “Protein Homeostasis” (2011 – 2012).

Special Editor for the journal Biochemistry and Cell Biology, Special Issue on AAA Proteins (February, 2010).

Editor of The Biomedical & Life Sciences Collection, Henry Stewart Talks Series on “Molecular Chaperones: Principles and Diseases” (2006 – 2007).

Research Lab

I started my group at the University of Toronto in 2000. The ultimate aim of our projects is to address the fundamental question of how molecular chaperones and ATP-dependent proteases modulate protein folding in the cell. To this end, we study the biochemical and biophysical basis of function of these molecular chaperones and proteases as well as their cellular roles in model systems including E. coli, yeast, and mammalian cells. We are also mapping what we call the chaperone interaction networks with the ultimate aim of identifying the rules that govern protein folding processes in the cell. Our group employs a battery of approaches including cell biological, biochemical, biophysical, proteomics, and bioinformatics tools. Our work also has a translational aspect leading to the development of novel antibiotics and anticancers.

Learn more: Houry Lab

Research Description

Cellular Protein Homeostasis Research Group

There are three main projects in my laboratory. One is on the Hsp90-R2TP complex, the second one is on the Clp system, and the third one is on mapping the chaperone interaction network. The three projects deal with the common theme of cellular stress response. We are also interested in identifying compounds that target protein cellular homeostasis and that can be developed as anticancers or antibacterials.


Through a large-scale proteomics approach, we discovered that 10% of the yeast proteome physically or genetically interacts with Hsp90. Furthermore, we identified new conserved cofactors of the chaperone. Two of these cofactors, which we termed Tah1 and Pih1, were found to link Hsp90 to rRNA processing pathways. This is the first demonstration of a link between chaperones and rRNA processing. Furthermore, Tah1 and Pih1 were found to form a tight complex with the essential helicases Rvb1 and Rvb2. We found that Rvb1 and Rvb2 form a heterohexameric complex with ATPase and helicase activities. We termed the complex of Rvb1-Rvb2-Tah1-Pih1 as R2TP. We solved the structure of Tah1 by NMR and determined the electron microscopy structures of Rvb1/2. We also found that R2TP cycles between the nucleus and the cytoplasm depending on nutrient availability. Our efforts on this project are aimed at elucidating at the molecular level the ultimate effect of Hsp90 and R2TP on ribosome biogenesis. This project sheds further insights into the role of Hsp90, Rvb1, and Rvb2 in cancer.

Clp system

Our work on the Clp system provided important insights into the function of this chaperone-protease system, especially as regards to its structure and dynamics. Our initial work concentrated on ClpXP from E. coli. ClpX is a hexameric ATP-dependent unfoldase chaperone, while ClpP is a serine protease that forms a cylindrical tetradecamer with narrow axial pores for substrate entry. In the ClpXP complex, ClpX binds target substrates, unfolds them and threads them into ClpP for degradation. We discovered that the mechanism of release of degradation products from the cylindrical protease ClpP is through the formation of transient equatorial side pores that allow for peptide egress. We also discovered compounds that deregulate ClpP and that have antibacterial activity. Hence, our research in this field sheds novel insights into bacterial infectivity.

We subsequently provided a comprehensive analysis of the Clp chaperones and protease in the human malaria parasite Plasmodium falciparum. The parasite was found to contain four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC, and PfClpM. In addition, one PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Both PfClpP and PfClpR form mostly homoheptameric rings. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer. We also solved the X-ray structure of PfClpR. Our data suggest the presence of a ClpCRP complex in P. falciparum.

Mapping chaperone interaction networks

Molecular chaperones are essential components of a quality control machinery present in the cell. They can either aid in the folding and maintenance of newly translated proteins or they can lead to the degradation of misfolded and destabilized proteins. They are also known to be involved in many cellular functions, however, a detailed and comprehensive overview of the interactions between chaperones and their cofactors and substrates is still absent. The heat shock proteins Hsp90, Hsp70/Hsp40, and Hsp60/Hsp10 are typical chaperone systems that are highly conserved across organisms. In this project, we are carrying out systematic mapping of the chaperone interaction networks using a wide range of proteomic and genomic methods. The ultimate goal of the project is to determine the mechanisms that govern protein homeostasis inside the cell.

Awards & Distinctions

2015 — Visiting Scientist Award, National Research Foundation of South Africa
2011 — Tokyo Biochemical Research Foundation Award
2001-2006 — Canadian Institutes of Health Research New Investigator
2002-2005 — Premier’s Research Excellence Award
1997-2000 — Fellow of the Max-Planck-Institute
1996-1997 — Fellow of the Howard Hughes Medical Institute

Courses Taught

BCH374Y Research Project in Biochemistry
JBB2026H Protein Structure, Folding and Design
BCH473Y Advanced Research Project in Biochemistry
BCH340H Proteins: from Structure to Proteomics


View all publications on PubMed

The MoxR AAA+ ATPase RavA and its Cofactor ViaA Interact with and Modulate the Activity of the Fumarate Reductase Complex during Anaerobiosis in Escherichia coli
Wong, K. S., Bhandari, V., Janga, S. C., & Houry, W. A.
Journal of Molecular Biology 429(2), 324–344 (2017)  Read

Mechanism of Amyloidogenesis of a Bacterial AAA+ Chaperone
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.
Structure 24(7), 1095–1109 (2016)  Read

Nutritional Status Modulates Box C/D snoRNP Biogenesis by Regulated Subcellular Relocalization of the R2TP Complex
Kakihara, Y., Makhnevych, T., Zhao, L., Tang, W., & Houry, W. A.
Genome Biology 15(7): 404, 1-20 (2014)  Read

Structural Insights into the Inactive Subunit of the Apicoplast-Localized Caseinolytic Protease Complex of Plasmodium falciparum
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.
The Journal of Biological Chemistry 288(2), 1022-1031 (2013)  Read

Hsp110 is Required for Spindle Length Control
Makhnevych, T., Wong, P., Pogoutse, O., Vizeacoumar, F. J., Greenblatt, J. F., Emili, A., & Houry, W. A.
Journal of Cell Biology 198(4), 623-636 (2012)  Read

Activators of Cylindrical Proteases as Antimicrobials: Identification and Development of Novel Small Molecule Activators of the ClpP Protease
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.
Chemistry & Biology 18(9), 1167–1178 (2011)  Read

Linkage between the Bacterial Acid Stress and Stringent Responses Revealed by the Structure of the Inducible Lysine Decarboxylase
Kanjee, U., Gutsche, I., Alexopoulos, E., Zhao, B., El Bakkouri, M., Thibault, G., Liu, K., Ramachandran, S., Snider, J., Pai, E. F., & Houry, W. A.
The EMBO Journal 30(5), 931-944 (2011)  Read