Brent Derry, PhD
Developmental & Stem Cell Biology
University of Toronto
Department of Molecular Genetics
Phone: 416-813-7654 ext. 301829
For more information, visit:
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.
- Using C. elegans to model human diseases
- Mechanisms of programmed cell death (apoptosis)
- Organ development
- DNA repair
- Cellular non-autonomy
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:
- Regulation of cep-1 dependent apoptosis.
- Non-autonomous control of germline apoptosis.
- Regulation of DNA damage-induced apoptosis by the insulin signaling pathway.
- Role of cep-1 in maintenance of genome stability.
- Role of cerebral cavernous malformation (CCM) genes in apoptosis and organ development.
Current Lab Members:
- Eric Chapman - Gradute Student
- Matthew Eroglu - Summer student
- Madhavi Gunda - Research technician
- Mat Hall - Graduate student
- Amir Keshvarpour - Summer student
- Ben Lant - Postdoctoral fellow
- Abigail Mateo - Graduate student
- Hidehiro Okura – Collaborating postdoctoral fellow (Rutka Lab)
- Swati Pal - Postdoctoral fellow
- Anh Tran – Postdoctoral fellow
- Evan Wallace - Graduate student
- Bin Yu - Research technician
Canadian Institutes for Health Research (CIHR)
- Molecular control of germline apoptosis in C. elegans
- Regulation of apoptosis by insulin signaling in C. elegans
- Molecular mechanisms of cerebral cavernous malformations (coPI with Dr. Anne-Claude Gingras)
Angioma Alliance Canada
- The genetic landscape of cerebral cavernous malformations
Angioma Alliance USA
- CCM3 Action - MarodoM Research Award (co-PI: Dr. Ian Scott)
For a complete list of publications, please see PubMed
Lant B, Derry WB. (2014) Immunostaining for Markers of Apoptosis in the Caenorhabditis elegans Germline. Cold Spring Harb Protoc. 2014(5).
Lant B, Derry WB. (2014) Analysis of Apoptosis in Caenorhabditis elegans. Cold Spring Harb Protoc. 2014(5).
Lant B, Derry WB. (2014) High-Throughput RNAi Screening for Germline Apoptosis Genes in Caenorhabditis elegans. Cold Spring Harb Protoc. 2014(4).
Lant B, Derry WB. (2014) Fluorescent Visualization of Germline Apoptosis in Living Caenorhabditis elegans.Cold Spring Harb Protoc. 2014(4).
Lant B, Derry WB. (2014) Visualizing apoptosis in embryos and the germline of Caenorhabditis elegans. Cold Spring Harb Protoc. 2014(3):278-83.
Lant B, Derry WB. (2014) Induction of germline apoptosis in Caenorhabditis elegans. Cold Spring Harb Protoc. 2014(3):271-7.
Baruah A, Chang H, Hall M, Yuan J, Gordon S, Johnson E, Shtessel LL, Yee C, Hekimi S, Derry WB, Lee SS. (2014) CEP-1, the Caenorhabditis elegans p53 homolog, mediates opposing longevity outcomes in mitochondrial electron transport chain mutants. PLoS Genet.10(2):e1004097.
Leprivier G, Remke M, Rotblat B, Dubuc A, Mateo AR, Kool M, Agnihotri S, El-Naggar A, Yu B, Prakash Somasekharan S, Faubert B, Bridon G, Tognon CE, Mathers J, Thomas R, Li A, Barokas A, Kwok B, Bowden M, Smith S, Wu X, Korshunov A, Hielscher T, Northcott PA, Galpin JD, Ahern CA, Wang Y, McCabe MG, Collins VP, Jones RG, Pollak M, Delattre O, Gleave ME, Jan E, Pfister SM, Proud CG, Derry WB, Taylor MD, Sorensen PH. (2013) The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation. Cell. 153(5):1064-79.
Lant B, Derry WB. (2013) Methods for detection and analysis of apoptosis signaling in the C. elegans germline. Methods. 61(2):174-82.
Jolliffe AK, Derry WB. (2013) The TP53 signaling network in mammals and worms. Briefings in Functional Genomics. 12(2):129-41.
Perrin AJ, Gunda M, Yu B, Yen K, Ito S, Forster S, Tissenbaum HA, Derry WB. (2013) Noncanonical control of C. elegans germline apoptosis by the insulin/IGF-1 and Ras/MAPK signaling pathways. Cell Death & Differentiation. 20(1):97-107.
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.