Dr. Mark Nachtigal received his B.Sc. (Biology) and Ph.D. (Molecular Endocrinology) degrees from the University of Manitoba. His post-doctoral research was conducted in Dr. Holly Ingraham’s laboratory at the University of California, San Francisco in the area of mammalian reproductive tract development. Throughout his graduate and post-graduate training his research projects retained a link to human reproductive cancer biology.
In 1998, Dr. Nachtigal was recruited to Dalhousie University as the Rossetti Scholar for Cancer Research to study human epithelial ovarian cancer (EOC). While at Dalhousie University he served as the co-chair of the Nova Scotia Cancer Research Training Program (2006-08) and as a member of the CIHR Institute of Cancer Research Advisory Board. Dr. Nachtigal returned to Manitoba in 2010 to continue his research on EOC.
He is currently an Associate Professor in the Departments of Biochemistry & Medical Genetics, and Obstetrics, Gynecology, and Reproductive Sciences, as well as being a Senior Scientist in the Research Institute in Oncology & Hematology at CancerCare Manitoba.
Biomedical and Translational program in human ovarian cancer
Epithelial ovarian cancer (EOC) is the fifth leading cause of death by cancer amongst women. Approximately 95 women in Manitoba will be diagnosed with EOC this year. If detected at early stages of the disease, the cure rate approaches 90%; however, >70% of women are diagnosed with advanced disease when rates of survival are closer to 30%. Even after initial successful responses to therapy, EOC recurs in ~85% of patients. Dr. Nachtigal’s laboratory uses a combination of cellular and molecular approaches to investigate human EOC biology with a special interest in recurrent, chemotherapy-resistant disease. With the formation of the Manitoba Ovarian Biobanking Program (MOBP) and cooperation with national programs such as the Canadian Ovarian Cancer Research Consortium (COCRC), his lab will be able to more readily translate data obtained with EOC patient samples to clinically relevant results. The ability to isolate and use patient donated EOC cells in 3-dimensional primary culture provides a more relevant model to assess cell responses. In particular he, in collaboration with other University of Manitoba scientists, is focusing on investigating aspects of EOC cell biology and chromosomal instability (CIN), in addition to evaluating novel lipid-based therapeutics for treatment of chemoresistant EOC. This laboratory-based research is being complemented by epidemiologic studies to evaluate whether recent changes in clinical management have produced positive outcomes for the EOC population.
Chromosome instability (CIN) is a characteristic of many cancer types and is defined as a rate of change in which whole chromosomes or large chromosomal fragments are gained or lost. CIN is often associated with highly aggressive tumors, poor patient prognosis, and remains largely uncharacterized in HGSOC. In collaboration with Dr. Kirk McManus, we are investigating potential causes of CIN in high grade serous ovarian cancer (HGSOC). Dr. McManus and I co-supervise several trainees working on this project:
Chloe Lepage (M.Sc. student)
I am investigating the activity of two proteins that may contribute to development of CIN in HGSOC. To investigate this possibility, I am using a human fallopian tube secretory epithelial (FT) cell model. This is because FT cells are a cell of origin for HGSOC. I will change expression of these putative CIN-inducing proteins in FT cells, and then measure markers of CIN.
My project combines genetic, biochemical, and imaging microscopy techniques to characterize these early abnormal events and determine the impact they have on HGSOC development and progression. The results of this study will shed new light on the molecular origins of HGSOC and may reveal new targets to exploit for therapeutic benefit.
Claire Morden (M.Sc. student)
My goal is to track large-scale changes in the amount or organization of DNA in HGSOC patient samples. I will evaluate changes in CIN over time in the same patient. This is possible as some patients may develop ascites, a buildup of fluid in the abdomen, which is removed as part of the normal course of treatment. CIN can be evaluated in HGSOC cells isolated from repeat ascites samples. I will also apply CIN marker analysis, developed for solid tumor analysis in other cancers, to evaluate CIN in solid HGSOC samples on a tissue mircroarray (TMA). Once a CIN score is established for each patient sample, we can test whether CIN correlates with patient outcomes such as progression-free and overall survival.
My results will help us to understand HGSOC progression, and may facilitate development of a novel diagnostic or therapeutic algorithm to enhance pateint therapy.
Michaela Palmer (Co-op Student & Part-time Research Assistant)
I am participating in the HGSOC - CIN project through evaluation of an additional candidate CIN-inducing protein whose expression is recombinantly altered in the FT cell model.
Altman AD, G Lefas, L Power, P Lambert, R Lotocki, E Dean, MW Nachtigal. 2017 Rate of Appendiceal Metastasis with Non-Serous Epithelial Ovarian Cancer in Manitoba. Journal of Obstetrics & Gynaecology Canada. Accepted. IF = 1.34
Moraya AI, JL Ali, P Samadder, L Liang, L Coudiere-Morrison, TE Werbowetski-Ogilvie, M Ogunsina, F Schweizer, G Arthur, MW Nachtigal. 2017. Novel glycolipid agents for killing cisplatin-resistant human epithelial ovarian cancer cells. Accepted. Journal of Experimental and Clinical Cancer Research. IF = 4.357
Altman AD, P Lambert, AJ Love, D Turner, R Lotocki, E Dean, S Popowich, MW Nachtigal. 2017. Examining the effects of time-to-diagnosis, income, symptoms and incidental detection on overall survival in ovarian cancer: Manitoba Ovarian Cancer Outcomes (MOCO) study group. International Journal of Gynecological Cancer. Accepted. IF = 2.116
Penner-Goeke S, Z Lichtensztejn, M Neufeld, JL Ali, AD Altman, MW Nachtigal, KJ McManus. 2017. The Temporal Dynamics of Chromosome Instability in Ovarian Cancer Cell Lines and Primary Patient Samples. PLOS Genetics 13(4):e1006707. doi: 10.1371/journal.pgen.1006707. IF = 6.661
Lambert P, K Galloway, AD Altman, MW Nachtigal, D Turner. 2017. Ovarian cancer in Manitoba, Canada: Trends in incidence and survival (1992-2011). Current Oncology 24(2): e78-e84.
Love AJ, P Lambert, D Turner, R Lotocki, E Dean, S Popowich, AD Altman, MW Nachtigal. 2017. 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 5(1): E116-E122. doi:10.9778/cmajo.20160100 IF = 2.473
Power L, G Lefas, P Lambert, D Kim, D Evaniuk, R Lotocki, E Dean, S Popowich, MW Nachtigal, AD Altman. 2016. Hormone use after non-serous epithelial ovarian cancer: analysis of survival and recurrence. Obstetrics and Gynecology 127 (5): 837-847. IF = 5.175
Ali J, BJ Lagasse, AJ Minuk, AJ Love, AI Moraya, L Lam, G Arthur, SB Gibson, LC Morrison,
TE Werbowetski-Ogilvie, Y Fu, MW Nachtigal. 2015. Differential cellular responses induced by dorsomorphin and LDN-193189 in chemotherapy-sensitive and chemotherapy–resistant human epithelial ovarian cancer cells. International Journal of Cancer 136:E455-E469.
Thériault, BL, L. Portelance, A-M. Mes-Masson, and MW Nachtigal. Establishment of primary cultures from ovarian tumour tissue and ascites fluid. 2013. In Ovarian Cancer Research,
A Malek, Ed., Humana Press. Methods in Molecular Biology 1049: 323-36.
Research Publications: PubMed
Diagnostic Services Manitoba Research and Innovation Grant with K McManus and C Bicamumpaka
Creating a new ovarian cancer pathology resource for research and innovation in Manitoba ($15,000)
University Collaborative Research Program (UCRP) Operating Grant with K McManus and T Werbowetski-Ogilvie
Investigating chromosomal instability in ovarian cancer stem cells ($25,000)
Additional $25,000 matched by Department of Biochemistry & Medical Genetics, University of Manitoba.
CancerCare Manitoba Foundation (CCMF) Operating Grant with G Arthur and F Schweizer
Testing lipid-based therapy for drug-resistant ovarian cancer (Yr 1 $60,000, Yr 2 $60,000)
University of Manitoba
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