The Morin group works towards developing proteomic methods for protein function research and the global analysis of post-translational modifications (e.g., phospho, ubiquitin, methyl, acetyl) with expertise is in advanced proteomics methods, biochemistry and RNA processing. The research focuses on understanding the function of somatically mutated cancer genes, with an emphasis on proteins involved in the regulation of alternative splicing. Dr. Morin’s group also develops proteomic methods for ultra high proteome coverage and quantification of fresh-frozen paraffin-embedded (FFPE) tumour sections.

Location

CRC

We are located at Canada's Michael Smith Genome Sciences Centre, part of the BC Cancer Research Centre.

Address: 
675 West 10th Avenue 
Vancouver, British Columbia 
V5Z 1L3 

Projects

Selected Publications

De novo and cell line models of human mammary cell transformation reveal an essential role for Yb-1 in multiple stages of human breast cancer

Cell Death and Differentiation
Sylvain Lefort, Amal El-Naggar, Susanna Tan, Shane Colborne, Gian Luca Negri, Davide Pellacani, Martin Hirst, Barry Gusterson, Gregg B Morin, Poul H Sorensen, Connie J Eaves

Breast cancer heterogeneity has made it challenging to identify mechanisms critical to the initial stages of their genesis in vivo. Here, we sought to interrogate the role of YB-1 in newly arising human breast cancers as well as in established cell lines. In a first series of experiments, we found that short-hairpin RNA-mediated knockdown of YB-1 in MDA-MB-231 cells blocked both their local tumour-forming and lung-colonising activity in immunodeficient mice. Conversely, upregulated expression of YB-1 enhanced the poor in vivo tumorigenicity of T47D cells. We then found that YB-1 knockdown also inhibits the initial generation in mice of invasive ductal carcinomas and ductal carcinomas in situ from freshly isolated human mammary cells transduced, respectively, with KRASG12D or myristoylated-AKT1. Interestingly, increased expression of HIF1α and G3BP1, two YB-1 translational targets and elements of a stress-adaptive programme, mirrored the levels of YB-1 in both transformed primary and established MDA-MB-231 breast cancer cells.

Loss of m1acp3Ψ Ribosomal RNA Modification Is a Major Feature of Cancer

Cell Reports
Artem Babaian, Katharina Rothe, Dylan Girodat, Igor Minia, Sara Djondovic, Miha Milek, Sandra E Spencer Miko, Hans-Joachim Wieden, Markus Landthaler, Gregg B Morin, Dixie L Mager

The ribosome is an RNA-protein complex that is essential for translation in all domains of life. The structural and catalytic core of the ribosome is its ribosomal RNA (rRNA). While mutations in ribosomal protein (RP) genes are known drivers of oncogenesis, oncogenic rRNA variants have remained elusive. We identify a cancer-specific single-nucleotide variation in 18S rRNA at nucleotide 1248.U in up to 45.9% of patients with colorectal carcinoma (CRC) and present across >22 cancer types. This is the site of a unique hyper-modified base, 1-methyl-3-α-amino-α-carboxyl-propyl pseudouridine (m1acp3Ψ), a >1-billion-years-conserved RNA modification at the peptidyl decoding site of the ribosome. A subset of CRC tumors we call hypo-m1acp3Ψ shows sub-stoichiometric m1acp3Ψ modification, unlike normal control tissues. An m1acp3Ψ knockout model and hypo-m1acp3Ψ patient tumors share a translational signature characterized by highly abundant ribosomal proteins. Thus, m1acp3Ψ-deficient rRNA forms an uncharacterized class of “onco-ribosome” which may serve as a chemotherapeutic target for treating cancer patients.

Staff

Dr. Christopher Hughes

Mass Spectrometry Service Specialist

Dr. Grace Cheng

Staff Scientist

Dr. Gian Luca Negri

Staff Scientist

Genny Trigo-Gonzalez

Research Technician

Grant McNair

Projects Manager

Postdoctoral Fellows

Dr. Brian Mooney

Postdoctoral Fellow

Trainees

Richard Chen

Graduate Student

Ryan Riley

Graduate Student

Xander Yin

Graduate Student

Fraser Johnson

Graduate Student

Caitlyn De Jong

Graduate Student

Karama Asleh

Visiting Graduate Student

Jenny Zhong

Graduate Student

Yueyang Li

Graduate Student

Siyu Miao

Graduate Student

Jiahua Tan

Graduate Student
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