Manitoba Ovarian Cancer Research Team (MOCR)

High-grade serous ovarian cancer (HGSOC) is the most common and lethal gynecological cancer worldwide. Due to the lack of early detection methods, HGSOC is typically diagnosed at advanced stages, when chemotherapy may be the only effective treatment option for patients. Unfortunately, the majority of patients experience relapse with chemotherapy-resistant disease contributing to survival rates that have changed little over the past ~40 years.  These facts highlight an urgent need for novel insight and new treatment options to more effectively combat recurrent disease. To realize this goal, multidisciplinary research aimed at gaining a greater understanding of the mutated genes giving rise to chemotherapy resistant HGSOC is required before new prognostic or therapeutic strategies can be developed that exploit those origins to improve the lives of those women living with HGSOC.

We created the Manitoba Ovarian Cancer Research (MOCR) team from experts in cancer genetics, cell biology, computational biology, gynecologic oncology, and the health outcomes analytic expertise of the Manitoba Ovarian Cancer Outcomes (MOCO) study group. The team’s goal is to perform innovative HGSOC research in Manitoba to transform clinical potential for women diagnosed with sporadic or familial HGSOC. This is vital to develop innovative and personalized treatment strategies to improve the lives and outcomes of women living with HGSOC.

Team Members:

Dr. Mark Nachtigal, PhD (Co-Lead of MOCO and MOCR)
Senior Scientist; Research Institute in Oncology & Hematology CancerCare Manitoba 
Associate Professor; Department of Biochemistry & Medical Genetics
Associate Professor; Obstetrics, Gynecology & Reproductive Sciences
College of Medicine, Rady Faculty of Health Sciences
University of Manitoba

Dr. Kirk McManus, PhD (Co-Lead of MOCR)
Senior Scientist; Research Institute in Oncology & Hematology CancerCare Manitoba 
Professor; Department of Biochemistry & Medical Genetics
College of Medicine, Rady Faculty of Health Sciences
University of Manitoba

Dr. Alon Altman, MD (Co-Lead of MOCO)
Member, Research Institute in Oncology & Hematology CancerCare Manitoba 
Professor, Obstetrics, Gynecology & Reproductive Sciences
College of Medicine, Rady Faculty of Health Sciences
University of Manitoba

Dr. Sarah Kean, MD, FRCSC
Assistant Professor – Division of Gynecologic Oncology, Dept of Obstetrics, Gynecology, and Reproductive Sciences
College of Medicine, Rady Faculty of Health Sciences – University of Manitoba

Dr. Bernie Chodirker, MD, FRCPC, FCCMG
Medical Director of Genetics and Metabolism – Winnipeg Regional Health Authority
Professor – Departments of Pediatrics and Child Health, Biochemistry & Medical Genetics
College of Medicine, Rady Faculty of Health Sciences – University of Manitoba

Ms. Kim Serfas, BSc, MSc, CCGC
Genetic Counsellor – Hereditary Cancer Clinic Winnipeg Regional Health Authority
Lecturer - Department of Biochemistry & Medical Genetics
College of Medicine, Rady Faculty of Health Sciences – University of Manitoba

Dr. Pingzhao Hu, PhD
Affiliate Scientist, Research Institute in Oncology & Hematology CancerCare Manitoba 
Assistant Professor of Bioinformatics - Department of Biochemistry and Medical Genetics
College of Medicine, Rady Faculty of Health Sciences
University of Manitoba

Dr. Janilyn Arsenio, PhD
Canada Research Chair in Systems Biology of Chronic Inflammation
Assistant Professor, Departments of Internal Medicine & Immunology
Rady Faculty of Health Science, Max Rady College of Medicine
University of Manitoba
Manitoba Centre for Proteomics and Systems Biology

Mr. Pascal Lambert; MSc
Health Outcomes Analyst, CancerCare Manitoba

Support for Research Provided By:

2020-2022: Cancer Research Society and Ovarian Cancer Canada (grant # 25040). “Exploring and exploiting aberrant RBX1 expression in high-grade serous ovarian cancer”. $60,000 per year (co-investigators Drs. Kirk McManus and Mark Nachtigal).

2020-2022: CancerCare Manitoba Foundation (CCMF). “Studies on the mechanism of action of L-diamino-based Glycosylated Antitumor Ether Lipids (GAELs) for the treatment of high grade serous ovarian cancer”. $75,000 per year (co-investigators Drs. Mark Nachtigal, Gilbert Arthur, Frank Schweizer and Kirk McManus).

2020-2022: University Collaborative Research Program (UCRP), and Faculty of Science Collaborative Research Program. Detection and investigation of drug resistance in ovarian cancer by electrochemistry. $37,000 (co-investigators Drs. Sabine Kuss and Mark Nachtigal).

2020-2021: University Research Grants Program (URGP). “Generating a mouse with floxed Skp1 to model human cancer conditions”. $10,000 (co-investigators Drs. Mark Nachtigal, Kirk McManus and Barb Triggs-Raine).

2019-2021: CancerCare Manitoba Foundation (CCMF) Multidisciplinary Team Research Operating Grant. “Examining the biomedical, clinical, and health outcome impacts of homology directed repair (HDR) in high-grade serous ovarian cancer (HGSOC)”. $150 000 per year (co-investigators Drs. Kirk McManus, Mark Nachtigal, Alon Altman and Cyrille Bicamumpaka).

2018-2019: University of Manitoba bridge funding. Preclinical studies to develop L-glycosylated antitumor ether lipids (L-GAELs) as novel agents for the treatment of drug-resistant ovarian cancer. (co-investigators Drs. Gilbert Arthur, Mark Nachtigal, and Frank Schweizer) – completed

2017-2019: Cancer Research Society, Inc. “Investigating mechanisms of chromosomal instability in human ovarian cancer”. $60 000 per year (co-investigators Drs. Kirk McManus, Mark Nachtigal, and Cyrille Bicamumpaka) – completed

2017-2019: Diagnostic Services Manitoba Research and Innovation Grant. “Creating a new ovarian cancer pathology resource for research and innovation in Manitoba”. $15 000. (co-investigators Drs. Kirk McManus, Mark Nachtigal and Cyrille Bicamumpaka) – completed

5-Year Publications: (**indicates trainee)

1. **Lepage CC, **Palmer MCL, **Farrell AC,** Neudorf NM, Lichtensztejn Z, Nachtigal MW, McManus KJ. Reduced SKP1 and CUL1 expression underlies increases in Cyclin E1 and chromosome instability in cellular precursors of high-grade serous ovarian cancer. Br J Cancer. 2021 Mar 17. doi: 10.1038/s41416-021-01317-w. Epub ahead of print. PMID: 33731859.
2. **Morden CR, **Farrell AC, Sliwowski M, Lichtensztejn Z, Altman AD, Nachtigal MW, McManus KJ. Chromosome instability is prevalent and dynamic in high-grade serous ovarian cancer patient samples. Gynecol Oncol. 2021 Mar 10:S0090-8258(21)00199-2. doi: 10.1016/j.ygyno.2021.02.038. Epub ahead of print. PMID: 33714608.
3. **Bungsy M, **Palmer MCL, **Jeusset LM, **Neudorf NM, Lichtensztejn Z, Nachtigal MW, McManus KJ. Reduced RBX1 expression induces chromosome instability and promotes cellular transformation in high-grade serous ovarian cancer precursor cells. Cancer Lett. 2021 Mar 1;500:194-207. doi: 10.1016/j.canlet.2020.11.051. Epub 2020 Dec 5. PMID: 33290867
4. Heinze K, Hölzer M, Ungelenk M, Gerth M, Thomale J, Heller R, **Morden CR, McManus KJ, Mosig AS, Dürst M, Runnebaum IB, Häfner N. RUNX3 Transcript Variants Have Distinct Roles in Ovarian Carcinoma and Differently Influence Platinum Sensitivity and Angiogenesis. Cancers (Basel). 2021 Jan 26;13(3):476. doi: 10.3390/cancers13030476. PMID: 33530588
5. Luu H TL, MW Nachtigal, S Kuss. 2020. Electrochemical Characterization of Carboplatin at Unmodified Platinum Electrodes and its Application to Drug Consumption Studies in Ovarian Cancer Cells. Journal of Electroanalytical Chemistry. 872:114253. doi.org/10.1016/j.jelechem.2020.114253
6. Altman AD, P Lambert, E Dean, C Robinson, S Popowich, MW Nachtigal, S Kean. 2020. Response to multi-line chemotherapy in non-serous epithelial ovarian cancer. Journal of Obstetrics and Gynaecology Canada 42(10): 1217-1222. doi: 10.1016/j.jogc.2020.04.008
7. Ogunsina M, P Samadder, T Idowu, MW Nachtigal, F Schweizer, G Arthur. 2020. Syntheses of L-Rhamnose linked amino glycerolipids and their cytotoxic activities against human cancer cells. Molecules 25:566. doi: 10.3390/molecules25030566
8. **Lepage CC, **CR Morden, **MCL Palmer, MW Nachtigal, KJ McManus. 2019. Detecting Chromosome Instability in Cancer: Approaches to Resolve Cell-to-Cell Heterogeneity. Cancers. 11: 226. Review. doi:10.3390/cancers11020226.
9. Martin LTP, Nachtigal MW, Selman T, Nguyen E, Salsman J, Dellaire G, Dupré DJ. Bitter taste receptors are expressed in human epithelial ovarian and prostate cancers cells and noscapine stimulation impacts cell survival. Mol Cell Biochem. 2019 Apr;454(1-2):203-214. doi: 10.1007/s11010-018-3464-z. Epub 2018 Oct 22. PMID: 30350307.
10. Page C, Rahimi K, Köbel M, Tonin PN, Meunier L, Portelance L, Bernard M, Nelson BH, Bernardini MQ, Bartlett JMS, Bachvarov D, Gotlieb WH, Gilks B, McAlpine JN, Nachtigal MW, Piché A, Watson PH, Vanderhyden B, Huntsman DG, Provencher DM, Mes-Masson AM. Characteristics and outcome of the COEUR Canadian validation cohort for ovarian cancer biomarkers. BMC Cancer. 2018 Mar 27;18(1):347. doi: 10.1186/s12885-018-4242-8. PMID: 29587661
11. Altman AD, Lefas G, Power L, Lambert P, Lotocki R, Dean E, Nachtigal MW. Rate of Appendiceal Metastasis with Non-Serous Epithelial Ovarian Cancer in Manitoba. J Obstet Gynaecol Can. 2018 Feb;40(2):180-185. doi: 10.1016/j.jogc.2017.05.038. Epub 2017 Aug 18. PMID: 28826644.
12. **Mayba J, Lambert P, Turner D, Lotocki R, Dean E, Popowich S, Altman AD, Nachtigal MW; Manitoba Ovarian Cancer Outcomes (MOCO) Study Group. Examining the Selection Criteria of Neoadjuvant Chemotherapy Patients. J Obstet Gynaecol Can. 2018 May;40(5):595-603. doi: 10.1016/j.jogc.2017.09.018. Epub 2017 Dec 21. PMID: 29276164.
13. Altman AD, Lambert P, Love AJ, Turner D, Lotocki R, Dean E, Popowich S, Nachtigal MW. Examining the Effects of Time to Diagnosis, Income, Symptoms, and Incidental Detection on Overall Survival in Epithelial Ovarian Cancer: Manitoba Ovarian Cancer Outcomes (MOCO) Study Group. Int J Gynecol Cancer. 2017 Oct;27(8):1637-1644. doi: 10.1097/IGC.0000000000001074. PMID: 28704327.
14. **Moraya AI, Ali JL, Samadder P, Liang L, Morrison LC, Werbowetski-Ogilvie TE, Ogunsina M, Schweizer F, Arthur G, Nachtigal MW. Novel glycolipid agents for killing cisplatin-resistant human epithelial ovarian cancer cells. J Exp Clin Cancer Res. 2017 May 12;36(1):67. doi: 10.1186/s13046-017-0538-9. PMID:28499442
15. Lambert P, Galloway K, Altman A, Nachtigal MW, Turner D. Ovarian cancer in Manitoba: trends in incidence and survival, 1992-2011. Curr Oncol. 2017 Apr;24(2):e78-e84. doi: 10.3747/co.24.3312. Epub 2017 Apr 27. PMID: 28490929
16. **Penner-Goeke S, Lichtensztejn Z, Neufeld M, Ali JL, Altman AD, Nachtigal MW, McManus KJ. The temporal dynamics of chromosome instability in ovarian cancer cell lines and primary patient samples. PLoS Genet. 2017 Apr 4;13(4):e1006707. doi: 10.1371/journal.pgen.1006707. PMID: 28376088
17. Love AJ, Lambert P, Turner D, Lotocki R, Dean E, Popowich S, Altman AD, Nachtigal MW. Diagnostic and referral intervals for Manitoba women with epithelial ovarian cancer - the Manitoba Ovarian Cancer Outcomes (MOCO) study group: a retrospective cross-sectional study. CMAJ Open. 2017 Feb 7;5(1):E116-E122. doi: 10.9778/cmajo.20160100. PMID: 28401127