Dr. Rottapel is a Senior Scientist at the Princess Margaret Cancer Centre where he holds the Amgen Chair for Cancer Research. He is a Professor in the Departments of Medicine, Immunology and Medical Biophysics at the University of Toronto. After completing his medical studies at George Washington University, the NIH and UCLA, he pursued his postdoctoral studies with Allan Bernstein at the Lunenfeld Research Institute in Toronto and with Patrice Dubreuil at INSERM, France. Dr. Rottapel is a clinical rheumatologist at St. Michael's Hospital, University of Toronto. His clinical expertise is in monogenic autoinflammatory disorders and the autoimmune adverse effect resulting from checkpoint inhibitors in cancer patients.

Dr. Rottapel’s research interests lies in the elucidation of signal transduction pathways in cancer, immune and bone cells. He has focussed on developing a comprehensive map of ovarian cancer essential genes using whole genome RNAi and CRISPR technology. This approach has provided insight into novel drivers resulting from the widespread gene copy number aberrations observed in ovarian cancer and the identification of emergent vulnerabilities associated with adaptation pathways required to buffer cancer associated stress states. Several of these targets are being developed for potential new therapeutic strategies in ovarian and pancreatic cancer. A second area of interest has been the elucidation of the molecular basis for a rare autosomal human disease called Cherubism. The adapter protein 3BP2 is mutated in Cherubism. The Rottapel lab has shown that 3BP2 has pleiotrophic function controlling bone homeostasis, immune cell function and scavenger receptor activation.

Jose La Rose has been the lab manager for Dr. Rottapel for approximately 24 years. His background is molecular biology at the University of Toronto. The Rottapel lab acquires data using a wide range of techniques so his experience has grown beyond that of molelcular biology. He started with a passion for benchwork and this remains the same to this day.

Molly Udaskin attended the University of Guelph where she received a B.Sc. in Molecular Biology and Genetics and her M.Sc. in Molecular and Cellular Biology (focusing on virology). Her master's thesis examined the proteolytic processing of a large replicase polyprotein produced by a virus that infects grape plants.

Molly has been working in the Rottapel lab since April 2017. She is performing large-scale, genome wide screens on ovarian cancer cell lines using the CRISPR-Cas9 technology. Molly is also attempting to generate 3D organoid cultures from patient samples through the Princess Margaret Living Biobank.

Ren Sun graduated from the University of Toronto, majoring in Biomedical Toxicology. She then continued to pursue her graduate degree at the University of Toronto, where she received her M.Sc. in Pharmacology - the bulk of her graduate work looking at the pharmacogenomics of drug response in head and neck cancer.

Ren provides bioinformatics assistance for projects within the lab - be it analysis of sequencing data or those of a more complex statistical nature.

Dr. Ioannis Dimitriou received his PhD in autoimmune diseases from the Medical School, University of Athens, Greece. Before he join Dr Rottapel’s he was a postdoctoral fellow at Drexel School of Medicine, Philadelphia, USA, where he worked on the regulation of CD8+ T cell responses during infections, such as Influenza and HIV. His scientific interests lay in the understanding of the regulation of immune responses and specifically CD8+ T cell activation, differentiation and development and their implications in inflammation and tumour immunology.

His work in the Rottapel lab has been focused on the role of the 3BP2 adapter protein in regulating TCR signalling during CD8+ T cell activation and differentiation, as well as its role in other type of immune cells such as macrophages and neutrophils. In addition, he studies the functional implications of CD28-dependent translational control during T cell activation and the interaction between translational control mechanisms and mitochondrial activity during CD8+ T cell activation.

Dr. Helen Burston received her PhD in Medical Genetics from the University of British Columbia, Canada at the Centre for Molecular Medicine and Therapeutics. Her doctoral thesis involved studying how underlying defects in vesicle transport contribute to human disease. This led to the identification of new proteins and complexes regulating endocytic recycling in the yeast Saccharomyces cerevisiae. She joined Dr. Rottapel’s lab in 2012 to identify essential GPCRs in High Grade Serous Ovarian Cancer (HGSOC), using functional genetic screens.

The focus of Dr. Burston’s postdoctoral work is on determining the role of the relaxin hormonal signaling pathway in HGSOC. This work has led to the discovery of an autocrine loop involving relaxin and its G-protein coupled receptor RXFP1 in maintaining the growth of cancer cells and tumors. Dr. Burston is now pursuing the development and testing of therapeutics targeting the relaxin pathway in preclinical models of HGSOC.

Dr. Kyle Francis received his PhD in Molecular and Clinical Medicine (Pathology) from the University of Edinburgh, Scotland at the Division of Pathology Laboratories. His doctoral thesis involved studying checkpoint kinases as therapeutics targets in ovarian cancer. This led to the identification of the checkpoint kinases as mediators of platinum resistance and phosphorylated CHEK1 as a poor prognostic biomarker, highlighting ovarian cancer’s characteristic of genomic instability. He joined the Rottapel lab in 2014 to identify new therapeutic vulnerabilities in high-grade serous ovarian cancer (HGSOC) using functional genomics.

Dr. Francis’ postdoctoral work involves studying the essential function of SMG1 kinase in HGSOC. SMG1 functions in an mRNA quality control pathway titled nonsense mediated mRNA decay to destroy damaged transcripts that would otherwise be translated into truncated and misfolded proteins. His research has identified a therapeutic window in HGSOC where SMG1 inhibition induces cell death and presents a unique set of MHC class I-associated neoantigens for tumour immune detection. Ongoing work involves studying the effect of SMG1 inhibition on ovarian cancer tumour growth and immune infiltration in vivo.

Dr. Jeanne Froehlich received her PhD from Paris Descartes University (France). During that time, she studied T-cell activation mechanisms. Her doctoral thesis focused on analyzing the molecular mechanism maintaining T-cell quiescence state, and in particular the role of Fam65b, a new transcriptional target of FoxO1, in this process.

She joined the lab in March 2018 to study the immunologic responses to ovarian cancer by using targeted drugs developed in the lab.

Dr. Oliver Kent completed his PhD in biochemistry at the University of Alberta in Edmonton investigating mechanisms of spliceosome assembly on pre-mRNAs. With an insatiable interest in RNA function and regulation, Dr. Kent pursued a post-doc at Johns Hopkins School of Medicine studying the dysregulation of micro-RNAs in pancreatic cancer. These studies resulted the identification of two miRNAs negatively regulated by the oncogene KRAS that were able to completely abrogate tumorigenesis of pancreatic cancer cells in vitro and in vivo.

Dr. Kent joined the Rottapel lab in 2012 to continue with studies involving pancreatic cancer and the role of KRAS regulated genes in the initiation and maintenance of this disease. Out recent studies have identified the RHOGEF ARHGEF2 as an essential component of the RAS transformation program and delineated the transcriptional regulation of the ARHGEF2 gene. In addition, we have found that KRAS regulates the expression of a micro-RNA called miR-31 which acts as an effector in oncogenic KRAS-mediated regulation of invasion-migration in pancreatic cancer cells.

Dr. Manpia Saha received her B.Tech. in Biotechnology from the West Bengal University of Technology in 2009. She earned her Ph.D. in 2016 under the supervision of Dr. Annapoorni Rangarajan from the Department of Molecular Reproduction, Development and Genetics at the Indian Institute of Science, India’s premier research institute. Her doctoral thesis examines the role of AMPK in cancer cells under matrix-deprived conditions. A major focus of her studies dealt with the crosstalk between two critical cellular kinases AMPK and Akt.

She joined the laboratory of Dr. Robert Rottapel in 2017 to pursue her post-doctoral training. She is interested in studying cellular signaling pathways. Her current research deals with investigating protein interaction and signaling mediated by KSR1.

Dr. Arokia Priyanka Vaz obtained her PhD from the University of Nebraska Medical Center, Nebraska, USA in 2015. During her graduate training, she worked on pancreatic cancer stem cell research. Her work focused on Pancreatic Differentiation 2 (PD2) or human Polymerase Associated Factor 1 (hPAF1). PD2 is a component of a multifunctional protein complex involved in the transcriptional elongation of genes, cell cycle regulation, stem cell maintenance, histone methylation, chromatin remodeling and tissue transdifferentiation. Dr. Vaz demonstrated that hPAF1 is required for pancreatic cancer stem cell maintenance and gemcitabine resistance.

In the fall of 2015, she joined Dr. Rottapel’s lab to pursue her post-doctoral research. She has embarked on an ambitious project to determine how the population dynamics of individual cancer cells behave under the selective pressure of sublethal doses of cisplatin over time. Her study involves lentivirus-based barcoding technology to examine cisplatin resistance by defining the clonal dynamics of 2 genetically related ovarian cancer cell lines. This project will aid in understanding cisplatin resistance mechanisms in OC, providing a framework for development of better treatment regimes. She received the UHN post-doctoral fellowship in 2017 for the above mentioned project. In addition, she is investigating the underlying mechanism of a serine threonine kinase in sensitizing ovarian cancer cells to cisplatin.

Arun is a PhD candidate in the Department of Medical Biophysics and graduated from McMaster University in 2011 with a B.Sc in Biochemistry. He then started in The Rottapel lab in the June 2011 as a summer student before starting as a graduate student in January 2012.

He is currently characterizing novel substrates and regulation of Tankyrases, members of the Poly ADP Ribose Polymerase (PARP) family of enzymes. Tankyrase modifies substrates through protein-protein interactions via its ankyrin domains and conjugates ADP-ribose chains to target proteins. These modifications are recognized by an E3 ligase called RNF146 that subsequently targets these multi-protein complexes for degradation by the proteasome. Tankyrases are involved in diverse areas of cell biology through its substrates 3BP2 (bone remodelling), axin1 ( WNT signalling), angiomotin (polarity), and telomere elongation (TRF1/TRF2) and my project aims to further broaden this knowledge. The adaptor proteins SH3BP5 and SH3BP5L have been identified as novel substrates through BioID mass spectrometry experiments. This protein family has been characterized as guanine exchange factors (GEF's) for the Rab11 class of small GTPases. Ongoing work seeks to determine how Tankyrase regulates Rab11 regulated processes through these GEF proteins.

Sasha is currently a PhD candidate in the Department of Medical Biophysics and graduated from McMaster University in 2013 with a B.Sc in Life Science and Biochemistry. During her undergraduate degree, she had the opportunity to work under the supervision of Dr. Lisa Robinson and Dr. Sergio Grinstein at the SickKids Research Institute for two summers, which inspired and propelled her into her current research focus.

After joining the Rottapel lab in January 2014, she began investigating the role of adaptor protein 3BP2 in atherosclerosis and the role that this protein plays in particular phagocytic-like processes. In addition, she is also studying the role that 3BP2 plays in mediating crucial actin dynamic structures in macrophages and osteoclasts. Lastly, she is exploring the function of 3BP2 in immunology of triggered, systemic inflammation, using a sensitized mouse model.

During her PhD, her projects have allowed her to become thoroughly knowledgeable on the mechanisms of lipid uptake, endocytic processes, cellular metabolic regulation and dynamic actin cytoskeletal rearrangments. Throughout her PhD, she has become proficient in confocal microscopy, live cell imaging, microdissectioning, in addition to a range of biochemical and cellular techniques.