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Brad Doble

Brad Doble

Principal Investigator

Canada Research Chair in Stem Cell Signalling

Associate Professor, Department of Biochemistry and Biomedical Sciences

Contact Information

Location: MDCL 5031
Email: dobleb@mcmaster.ca

Research

“Wnt signalling has been linked to numerous human diseases including several types of cancer, Alzheimer’s disease, schizophrenia, type II diabetes and obesity. Thus, it is important to understand the details of how Wnt signalling works, as this information will be valuable in developing or improving therapies for Wnt-associated diseases.”

Dr. Brad Doble’s research program is focused on studying normal and aberrant cell signalling in order to understand the mechanisms of tumorigenesis. The Doble lab is particularly interested in studying the Wnt signalling pathway and those cancers in which Wnt has been implicated – cancers including blood, breast, colon and lung.

The Doble lab is gaining new insights into Wnt signalling mechanisms through the use of gene knockout, and gene knock-in approaches. Another key approach used in Dr. Doble’s lab is proteomic analysis. In collaboration with other research groups, proteomic techniques are being used to investigate the mechanisms regulating Wnt signalling networks and to identify new Wnt pathway components.

Ultimately, Dr. Doble wants to further our understanding of the role of Wnt signalling in stem cell regulation and cancer. Through this work, Dr. Doble is seeking to develop targeted cancer therapies that will address the abnormal cell signalling networks required to initiate and sustain specific sub-types of cancer.

Projects

Demonstrating the ability of the Wnt pathway to suppress tumour progression in childhood medulloblastoma, thus establishing activated Wnt signaling as a novel treatment paradigm.

The potential to identify new pathway modulators that could be used in therapies for diseases in which the Wnt pathway is hyperactivated.

Isolating new targets for the development of novel cancer therapeutics that block β-catenin’s nuclear function.

Identifying Tcf/Lef partners that regulate their functional output has the potential to provide new therapeutic targets which could be exploited in cancers with hyperactive Wnt signalling.

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Lab Team

Picture Name Designation Focus Email More Info
Solen Abdulla Solen Abdulla Graduate Student
Victor Gordon Victor Gordon Graduate Student
Steven Moreira Steven Moreira Graduate Student
Caleb Seo Caleb Seo Graduate Student

Selected Publications

β-catenin enhances Oct-4 activity and reinforces pluripotency through a TCF-independent mechanism.

Kelly KF, Ng DY, Jayakumaran G, Wood GA, Koide H, Doble BW.

Cell Stem Cell. 2011 Feb 4; 8(2): 214-227.

"The fate and function of pluripotent cells are balanced by a complex regulatory network that determines whether ESCs and iPSCs remain pluripotent or differentiate. Doble and colleagues examine GSK-3-deficient ESCs and show that β-catenin participates in the switch from pluripotency toward differentiation along the neuroectoderm lineage. They also make the surprising finding that β-catenin can enhance Oct-4 activity without needing to interact with TCF..." - Editors' Notes, Cell Stem Cell

Functional redundancy of GSK-3α and GSK-3β in Wnt/β-catenin signaling shown by using an allelic series of embryonic stem cell lines.

Doble BW, Patel S, Wood GA, Kockeritz LK, Woodgett JR.

Developmental Cell. 2007 June 5; 12(6): 957-971.

"The enzymes GSK-3alpha and GSK-3beta regulate numerous cellular processes by controlling the function of over 100 putative substrates. By using genetic knockout approaches in ES cells, this study conclusively illustrates that GSK-3alpha and GSK-3beta are functionally interchangeable in Wnt/β-catenin signalling, which is essential for normal development and organismal homeostasis. Most prior Wnt literature had placed an undue focus on GSK-3beta, and had minimized the role of GSK-3alpha. This study was one of the first to support a major role for GSK-3 in the control of ES cell pluripotency and differentiation." - Dr. Brad Doble

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Support

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