For more information, visit: Derry Lab

Brief Biography

Dr. Brent Derry received his B.Sc. from Carleton University in 1989, his M.Sc. 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. 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 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.
5. Role of cerebral cavernous malformation (CCM) genes in apoptosis and organ development.

Current Lab Members:

• Madhavi Gunda, research technician
• Kristine Jolliffe, post-doctoral fellow
• Mehran Haeri, post-doctoral fellow
• Bin Yu, research technician
• Ben Lant, postdoctoral fellow
• Kelly Chin, undergraduate project student
• Yiwei Hu, undergraduate project student
• Alissa Nicolucci, undergraduate project student
  

External Funding

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

Publications

Ceccarelli DF, Laister RC, Mulligan VK, Kean MJ, Goudreault M, Scott IC, Derry WB, Chakrabartty A, Gingras AC, Sicheri F (2011). CCM3/PDCD10 Heterodimerizes with Germinal Center Kinase III (GCKIII) Proteins Using a Mechanism Analogous to CCM3 Homodimerization. Journal of Biological Chemistry, 286: 25056-25064.

Kean MJ, Ceccarelli DF, Goudreault M, Sanches M, Tate S, Larsen B, Gibson LC, Derry WB, Scott IC, Pelletier L, Baillie GS, Sicheri F, Gingras AC (2011). Structure-Function Analysis of Core STRIPAK Proteins: A signaling complex implicated in Golgi polarization. Journal of Biological Chemistry, 286: 25065-25075.

Ross AJ, Li M, Yu B, Gao MX, Derry WB (2011). The EEL-1 ubiquitin ligase promotes DNA damage-induced germ cell apoptosis in C. elegans. Cell Death & Differentiation, 18: 1140-1149.

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.

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. 

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).