MCMANUS
LABORATORY Cancer Research in Genome Stability
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Kirk J. McManus, PhD (Principal Investigator)

Associate Professor (March 2015 - present)

McManusPicture

Assistant Professor (June 2009 - March 2015)

Department of Biochemistry & Medical Genetics University of Manitoba

Senior Scientist (June 2009 - present)

Research Institute in Oncology & Hematology CancerCare Manitoba

Education/Training

Post-doctoral Fellowship - Michael Smith Laboratories, University of British Columbia, Vancouver, Canada

PhD (Oncology) - Cross Cancer Institute, University of Alberta, Edmonton, Canada (2004)

MSc (Human Genetics) - University of Manitoba, Winnipeg, Canada (1999)

BSc (Honors Genetics) - University of Manitoba, Winnipeg, Canada (1995)

Contact Information

Kirk.McManus@umanitoba.ca

Dr. Kirk McManus is an Associate Professor in the Department of Biochemistry and Medical Genetics at the University of Manitoba. He is also a Senior Scientist within the Research Institute of Oncology and Hematology (formerly the Manitoba Institute of Cell Biology) housed within CancerCare Manitoba. He received a BSc (1995) and an MSc (1999) from the University of Manitoba and moved to Edmonton, Alberta to conduct his PhD studies (1999) in Oncology under the supervision of Dr. Michael Hendzel. There he studied the regulation and dynamics of post-translational histone modifications and their influence on chromosome segregation. His post-doctoral studies were performed with Dr. Phil Hieter at the Michael Smith Laboratories in Vancouver, BC, where he utilized cross-species approaches to identify genes that regulate chromosome stability and characterize their impact on cancer development. Dr. McManus joined the University of Manitoba in June, 2009, and his research interests focus on identifying and characterizing genes that regulate chromosome stability in a cancer context and exploiting these characteristics to identify novel therapeutic targets. He currently couples genetics, biochemistry and cellular biology along with innovative digital imaging microscopy to identify both genes and targets of interest.

Laura Thompson (PhD Candidate)

Laura

Education/Training

BSc (Honors) - University of Manitoba, Winnipeg, Canada (2010)

Contact Information

Laura.Thompson@umanitoba.ca

Chromosome instability (CIN), an increase in the rate at which chromosomal aberrations occur, is observed in more than 80% of colorectal cancers and in practically all other tumor types. CIN is often associated with highly aggressive tumors, poor patient prognosis, and the acquisition of multi-drug resistance. However, the genes and the biological mechanisms responsible for regulating and maintaining chromosome stability within a cell are currently either unknown or poorly characterized. The purpose of my project is to identify and characterize these human CIN genes. Cross-species candidate gene analyses will provide homologs that I will be able to screen rapidly using a novel high-throughput screening platform in order to determine if they are putative human CIN genes. Once identified and validated, these genes will provide the basis for subsequent studies, allowing for greater understanding of the biological mechanisms of CIN as well as the pathogenesis of colorectal cancer or other cancers that also exhibit CIN.

Lucile Jeusset (PhD Candidate)

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MSc (Systemic & Synthetic Biology) - AgroParisTech, Paris, France (2015)

Contact Information

jeussetl@myumanitoba.ca

Two out of five Canadians are expected to develop cancer in their lifetime and 1 in 4 to die from cancer. To change these statistics, it is necessary to better understand the processes at play in the development of cancer. Chromosome instability (CIN) is an increase of the rate of errors causing the loss or gain of chromosomes during cell divisions. It is a driving force in tumor development and it is associated with the acquisition of multi-drug resistance and metastatic potential in tumors. Although CIN is widespread in cancer, the genes (CIN genes) and mechanisms involved in the development of CIN are not clearly understood. My project will focus on a putative human CIN gene, USP22. USP22 is a deubiquitinating enzyme, notably responsible for the deubiquitination of histone H2B. Mutations or deletion of USP22 have been reported in CRC and several other cancer types. Investigating the role USP22 has in the acquisition of CIN will improve our understanding of this critical hallmark of cancer and may identify new therapeutic possibilities to better combat the disease.

Nicole Wilkinson (MSc Candidate)

Education/Training

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BSc (Honors; Co-op) - University of Manitoba, Winnipeg, Canada (2015)

Contact Information

umwilk28@myumanitoba.ca

The progression of cancer to metastatic disease is often the cause of death in cancer patients. Therefore, identifying therapies that specifically target these metastatic cells is of high importance. One approach to find these targets is to identify synthetic lethal interactors of tumour suppressor genes. Once identified, these genes can become targets for treatment options. The DLC1 and DLC2 tumour suppressor genes are frequently deleted or silenced in many cancers including over 50% of breast cancers and 70% of colon cancers. DLC1 and DLC2 code for Rho GTPase activating proteins (RhoGAPs), and play a major role in the metastatic progression of cancers. In order to identify synthetic lethal partners, I am generating isogenic DLC-deficient and –proficient cell lines using both the CRISPR-Cas9 system and through expression of short-hairpin RNAs (shRNAs). With these cell lines I will be able to identify genes that when inhibited in DLC-deficient tumours will cause synthetic lethal killing of metastatic cells while having fewer deleterious effects on normal cells.

Chloe Lepage (MSc Candidate)

Chloe

Education/Training

BSc - University of Manitoba

Contact Information

lepagec@myumanitoba.ca

Many cancers exhibit an accelerated rate of chromosomal gains or losses, referred to as chromosome instability (CIN). The consequence of CIN is acquisition of numerous genetic alterations, some of which may be required for cancer progression, and therefore CIN is generally associated with aggressive cancers and poor patient outcome. Much of the research within the McManus laboratory focuses on studying the genes that regulate chromosome stability (i.e. CIN genes) in order to gain a better understanding of the abnormal biology that causes cancer and identify pathways that may be targeted for therapeutic benefit. In this regard, I am investigating two putative CIN genes that are believed to be implicated in the pathogenesis of multiple cancer types, including colorectal and ovarian cancers. By creating overexpression and underexpression models for these genes, I will characterize the impact they have on CIN and malignant transformation in cancer.

Manisha Bungsy (MSc Candidate)

Manisha

Education/Training

BSc - University of Manitoba

Contact Information

bungsym@myumanitoba.ca

Cancer is a devastating disease and its incidence continues to rise every year. In fact, cancer is the number one cause of death in Canada. In 2017, the Canadian Cancer Society estimates that ~206,200 new cancer cases will arise and an additional 80,800 deaths will occur. These statistics highlight the need for a better understanding of the underlying causes and mechanisms driving cancer development so that new therapies can be developed. Unfortunately, the underlying causes of cancer remain poorly understood. However, genome instability is believed to be one of the key players in the development of cancer, and it occurs in up to 95% of all cancers. Although there are numerous aberrant pathways leading to genome instability, chromosome instability (CIN) is of particular interest as it occurs in most cancers, including ~85% of all colorectal cancers. My project aims to identify the underlying causes leading causing CIN and the development of cancer. Identifying the abnormal mechanisms causing CIN will aid in the discovery of novel therapeutic targets to improve the lives and outcomes for those diagnosed with cancer.

Michaela Palmer (Undergraduate Student & Part-time Research Assistant)

Education/Training

Michaela

BSc - University of Manitoba

Contact Information

palmerm3@myumanitoba.ca

Allison Baergen (BSc Medicine Student)

Allison

Education/Training

BSc - University of Winnipeg

Contact Information

baergeak@myumanitoba.ca

Tarik Leylek (BSc Medicine Student)

Tarik

Education/Training

BSc - University of Manitoba

Contact Information

umleylet@myumanitoba.ca

Zelda Lichtensztejn (Lab Manager)

Education/Training

Zelda

MSc (Human Genetics) - Tel-Aviv University, Tel Aviv, Israel (1994)

Contact Information

Zelda.Lichtensztejn@umanitoba.ca

FORMER MEMBERS

Yasamin Asbaghi (MSc Student)

Erin McAndrew (MSc Student)

Megan Neufeld (Co-op Student)

Allison Baergen (Undergraduate Summer Student & Research Assistant)

Tarik Leylek (Research Assistant)

Brent Guppy (PhD Student)

Signe Penner-Goeke (Undergraduate Summer Student & Research Assistant)

Amy Cisyk (MSc Student & Research Technician)

Babu Sajesh (Research Associate/Post-doctoral Fellow)

Aaron MacAulay (Undergraduate Summer Student/Project Student)

Dr. Raghvendra Vishwakarma (Research Associate)

Rehan Khan (Post-doctoral Research Fellow)

Brittany Kessler (Undergraduate Summer Student)

Laryssa Sawchuk (Undergraduate Summer Student/Project Student)

Nermin Moujani (Undergraduate Summer Student/Project Student)

Jeff Schachter (Undergraduate Student)

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