For more information, visit: Derry Lab

Brief Biography

Dr. Derry received his BSc from Carleton University in 1989, his MSc from McMaster University in 1992, and his PhD from the University of California, Santa Barbara, in 1997. His PhD thesis research with Dr. Leslie Wilson focused on elucidating the molecular mechanism by which the anti-cancer drug taxol suppresses microtubule dynamics, and the role of beta-tubulin isotypes in taxol resistance. Dr. Derry carried out his postdoctoral training from 1997 to 2003 in the laboratory of Dr. Joel Rothman at the University of California, Santa Barbara, where he identified and characterized the C. elegans p53 tumour suppressor gene.

In 2003 Dr. Derry joined the Research Institute as a scientist. His laboratory is focused on the application of genetics, functional genomics, and biochemical techniques to understand the p53 signaling network.

Research Interests

• Functional genomic and genetic analysis of the p53 signalling network
• Development of cancer models in C. elegans
• Apoptosis and cell cycle regulation
• Evolution of the p53 family
• Identification and characterization of negative regulators of cep-1.
• Characterization of genes and pathways that regulate germ cell apoptosis independent of cep-1.

Research Activities 

The broad goal of my research is to understand how tumour suppressor p53 integrates various stresses to modulate apoptosis, cell proliferation, development, and genomic stability. We are applying genetics and functional genomics techniques using the model organism Caenorhabditis elegans to identify genes that collaborate with p53 to control these cellular processes. Because C. elegans possesses a single p53 family member, cep-1, analysis is not complicated by the presence of family members p63 and p73, which have been shown to share some overlapping functions in vertebrate systems.

My team and I recently discovered a novel pathway that regulates germline apoptosis in parallel to cep-1 (Ito et al., 2010).  This new pathway contains the kri-1 gene, an orthologue of human CCM1/Krit1, which is frequently mutated in the neurovascular disease cerebral cavernous malformations.  Remarkably, kri-1 is required in the somatic tissue to promote apoptosis in the germline by a cell non-autonomous mechanism.  We are utilizing the powerful genetics of C. elegans to delineate this novel pathway and gain insight into how neighbouring tissues regulate the survival of damaged germ cells. 

Current projects in the lab include:

1. Regulation of cep-1 dependent apoptosis.
2. Non-autonomous control of germline apoptosis.
3. Regulation of DNA damage-induced apoptosis by the insulin signaling pathway.
4. Role of cep-1 in maintenance of genome stability.

Current Lab Members:

- Bin Yu, research technician
- Mary Xiangrong Gao, post-doctoral fellow
- Shu Ito, graduate student
- Andrew Perrin, graduate student
- Ying Zhu, undergraduate research assistant 
- May Yeo, Co-op student
- Peter Xu, summer student
- Stephen Forster, summer student

External Funding

Canadian Institutes for Health Research (CIHR)
Canada Foundation for Innovation
Ontario Research Fund

Publications

Ito S, Greiss S, Gartner A, Derry WB (2010) Cell-Nonautonomous Regulation of C. elegans Germ Cell Death by kri-1. Current Biology, 20: 333-338 abstract

Gao MX, Liao EH, Yu B, Wang Y, Zhen M, Derry WB. (2008) The SCFFSN-1 ubiquitin ligase controls germline apoptosis through CEP-1/p53 in C. elegans. Cell Death & Differentiation, 15: 1054-1062.

Taylor RC, Brumatti G, Ito S, Hengartner MO, Derry WB, Martin SJ. (2007). Establishing a blueprint for CED-3-dependent killing through identification of multiple substrates for this protease. Journal of Biological Chemistry, May 18; 282(20):15011-21. Epub 2007 Mar 19.

Quevedo C, Kaplan DR, Derry WB. (2007). AKT-1 regulates DNA-damage-induced germline apoptosis in C. elegans. Current Biology, 17: 286-292.

Derry WB, Bierings R, van Iersel M, Satkunendran T, Reinke V, Rothman JH. (2007). Regulation of developmental rate and germ cell proliferation in Caenorhabditis elegans by the p53 gene network. Cell Death & Differentiation. 14: 662-670. 2006 Dec 22; [Epub ahead of print]

Huyen Y, Jeffrey PD, Derry WB, Rothman JH, Pavletich NP, Stavridi ES, Halazonetis TD. (2004). Structural differences in the DNA binding domains of human p53 and its C. elegans ortholog CEP-1. Structure, 12: 1237-1243.

Dumontet C, Jaffrezou JP, Tsuchiya E, Duran GE, Chen G, Derry WB, Wilson L, Jordan MA, Sikic BI. (2004). Resistance to microtubule-targeted cytotoxins in a K562 leukemia cell variant associated with altered tubulin expression and polymerization. Bulletin du Cancer, 91: E81-E112.

Fukuyama M, Gendreau SB, Derry WB, Rothman JH. (2003). Essential embryonic roles of the CKI-1 cyclin-dependent kinase inhibitor in cell-cycle exit and morphogenesis in C. elegans. Developmental Biology, 260: 273 - 286.

Derry WB, Putzke AP, Rothman JH. (2001). Caenorhabditis elegans p53: role in apoptosis, meiosis, and stress resistance. Science, 294: 591-594. Published online September 13, 2001; 10.1126/science.1065486 (Science Express Reports).

Sugimoto A, Kusano A., Hozak RR, Derry WB, Zhu J, Rothman JH. (2000). Genomic regions required for programmed cell death in C. elegans: cell death can be uncoupled from nuclear proliferation. Genetics, 158: 237-252.

Derry WB, Wilson L, Jordan MA. (1998). The low potency of taxol at microtubule minus ends: Implications for its anti-mitotic and therapeutic mechanism. Cancer Research, 58: 1177-1184.

Derry WB, Wilson L, Khan IA, Ludueña RF, Jordan MA. (1997). Taxol differentially modulates steady-state dynamics of microtubules assembled from pure and mixed beta-tubulin isotypes. Biochemistry, 36: 3554-3562.

Jordan MA, Wendell K, Gardiner S, Derry WB, Copp H, Wilson L. (1996). Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Research, 56: 816-825.

Jaffrézou JP, Dumontet C, Derry WB, Duran GE, Chen G, Tsuchiya E, Wilson L, Jordan MA, Sikic BI. (1995). Novel mechanism of resistance to paclitaxel (Taxol) in human K562 leukemia cells by combined selection with PSC 833. Oncology Research, 7: 517-527.

Derry WB, Wilson L, Jordan MA. (1995). Substoichiometric binding of taxol suppresses microtubule dynamics. Biochemistry, 34: 2203-2211.