The Rottapel Lab


Our lab is interested in uncovering cancer signal transduction networks and elucidating mechanisms of their regulation. We are currently involved in a project to comprehensively map the genetic susceptibilities of serous ovarian cancer using functional genetic screens.

Interested and motivated postdoctoral fellows are highly encouraged to contact the lab and graduate students can apply through the Department of Medical Biophysics or the Department of Immunology at the University of Toronto.


RANKL coordinates multiple osteoclastogenic pathways by regulating expression of ubiquitin ligase RNF146.

April 2017
The Journal of Clinical Investigation

This study shows that RANKL-mediated suppression of RNF146 results in the stabilization of its substrates, thus acts as an inhibitory switch to control osteoclastogenesis and cytokine production and may be a control point underlying the pathogenesis of chronic inflammatory diseases.

Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer.

March 2017
Cell Reports

This study reveals cell-surface vulnerabilities associated with high grade serous carcinoma (HGSC), provides a framework for identifying therapeutic targets, and reports a role for tetraspanin CD151 in HGSC.

An oncogenic KRAS transcription program activates the RHOGEF ARHGEF2 to mediate transformed phenotypes in pancreatic cancer.

January 2017

Our results identify that oncogenic KRAS activates ARHGEF2 through a minimal RAS responsive promoter and that this transcription factor program is required for RAS transformation and provides mechanistic insight into the highly metastatic behavior of pancreatic cancer.

Reciprocal stabilization of ABL and TAZ regulates osteoblastogenesis through transcription factor RUNX2.

December 2016
The Journal of Clinical Investigation

Our study demonstrates an interplay between ABL and TAZ that controls the mesenchymal maturation program toward the osteoblast lineage and is mechanistically distinct from the established model of lineage-specific maturation.

GEF-H1 is necessary for neutrophil shear stress–induced migration during inflammation.

October 2016
The Journal of Cell Biology

Our results identify GEF-H1 as a component of the shear stress response machinery in neutrophils required for a fully competent immune response to bacterial infection.

Transcriptional Regulation of miR-31 by Oncogenic KRAS Mediates Metastatic Phenotypes by Repressing RASA1.

March 2016
Molecular Cancer Research

In the study miR-31 is identified as a RAS effector that enhances invasion-migration of pancreatic cancer cells via downregulation of the miR-31 target gene RASA1 and activation of RhoA. Expression of miR-31 is coupled to the expression of oncogenic KRAS and activity of the MAPK pathway.

Mechanistic insight into GPCR-mediated activation of the microtubule-associated RhoA exchange factor GEF-H1.

September 2014
Nature Communications

The coordinated displacement of GEF-H1 from microtubules by G-proteins and its dephosphorylation by PP2A demonstrate a multistep GEF-H1 activation and present a unique mechanism coupling GPCR signalling to Rho activation.

The RhoGEF GEF-H1 Is Required for Oncogenic RAS Signaling via KSR-1.

February 2014
Cancer Cell

Our results identify GEF-H1 as an amplifier of MAPK signaling and provide mechanistic insight into the progression of RAS mutant tumors.

The 3BP2 Adapter Protein Is Required for Chemoattractant-Mediated Neutrophil Activation.

July 2012
Journal of Immunology

Our results reveal an obligate requirement for the adapter protein 3BP2 in G protein-coupled receptor-mediated neutrophil function.

Mechanistic insight into the microtubule and actin cytoskeleton coupling through dynein-dependent RhoGEF inhibition.

March 2012
Molecular Cell

These studies demonstrate a pivotal role of Tctex-1 as a negative regulator of actin filament organization through its control of Lfc in the crosstalk between microtubule and actin cytoskeletons.

Essential gene profiles in breast, pancreatic, and ovarian cancer cells.

February 2012
Cancer Discovery

This study presents a resource of genome-scale, pooled shRNA screens for 72 breast, pancreatic, and ovarian cancer cell lines that will serve as a functional complement to genomics data, facilitate construction of essential gene profiles, help uncover synthetic lethal relationships, and identify uncharacterized genetic vulnerabilities in these tumor types.

Loss of Tankyrase-mediated destruction of 3BP2 is the underlying pathogenic mechanism of cherubism.

December 2011

Here we show that Tankyrase, a member of the poly(ADP-ribose)polymerase (PARP) family, regulates 3BP2 stability through ADP-ribosylation and subsequent ubiquitylation by the E3-ubiquitin ligase RNF146 in osteoclasts.

Structural basis and sequence rules for substrate recognition by Tankyrase explain the basis for cherubism disease

December 2011

Here we use a Tankyrase recognition motif to rationalize all known Tankyrase substrates and explains the basis for cherubism-causing mutations in the Tankyrase substrate 3BP2. Structural and sequence information allows us to also predict and validate other Tankyrase targets, including Disc1, Striatin, Fat4, RAD54, BCR, and MERIT40.

3BP2-deficient mice are osteoporotic with impaired osteoblast and osteoclast functions

August 2011
Journal of Clinical Investigation

These findings reveal an unanticipated role for the 3BP2 adapter protein in osteoblast function and in coordinating bone homeostatic signals in both osteoclast and osteoblast lineages.