Natasha Orr
Doctor of Philosophy in Reproductive and Developmental Sciences (PhD)
Research Topic
Educational videos on the pathophysiology of sexual pain in women with endometriosis
Michael Anglesio
Assistant Professor
Research Classification
Research Interests
Cancer of the Reproductive System
Host-Tumour Interaction
Endometriosis
Cancer Diagnosis and Detection
Immunotherapy
animal models of endometriosis and cancer
Cancer prevention
early detection biomarkers
endometriosis associated cancers
gene-expression and transcriptomics
genomics
Immunology
microenvironment
ovarian cancer etiology
Relevant Degree Programs
Affiliations to Research Centres, Institutes & Clusters
Research Options
I am interested in and conduct interdisciplinary research.
Research Methodology
molecular biology
Animal models
Next generation sequencing
transcriptomics
immunohistochemistry
laser capture microdissection
in vitro models of cancer
Recruitment
Doctoral students
Postdoctoral Fellows
Any time / year round
2021
Prospective students with independent/external funding may send their applications along with their research interests only if this aligns to current projects in the lab, please do not send application for projects unrelated to listed laboratory projects.
International and/or visiting student will be considered only from research groups where I have an active collaboration.
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Great Supervisor Week Mentions
Each year graduate students are encouraged to give kudos to their supervisors through social media and our website as part of #GreatSupervisorWeek. Below are students who mentioned this supervisor since the initiative was started in 2017.
Thank you to one of my co-supervisors @M_Anglesio for his guidance on my research project and patience in introducing me to the genetics of endometriosis #GreatSupervisor #UBC @UBC
Graduate Student Supervision
Master's Student Supervision (2010 - 2018)
Somatic cancer-driver mutations in endometriosis: implications beyond malignancy (2018)
Introduction: Endometriosis is a chronic, inflammatory gynecological disease characterized by the ectopic growth of endometrial-like tissue. Previous studies have established endometriosis as the precursor to clear cell and endometrioid ovarian carcinomas. The presence of somatic driver mutations in endometriosis is believed to represent early events in transformation, however our group has recently described the presence of such mutations in nearly one-quarter of cases of deep infiltrating endometriosis (DE) – a form of endometriosis that rarely progresses to malignancy. These mutations may play a fundamental role in the pathogenesis of endometriosis outside of the context of cancer, however it is unclear whether they occur in other forms of endometriosis or the eutopic endometrium – the likely tissue of origin for endometriosis. The purpose of my study is to: 1) analyze and compare the mutational profiles of DE and incisional (iatrogenic; IE) endometriosis and 2) characterize somatic cancer-drivers that exist in the eutopic endometrium and determine whether the presence of such mutations reflect the aging of this tissue.Methods: I macrodissected endometriosis tissue from women with IE or DE. Extracted DNA was analyzed by targeted sequencing and mutations were orthogonally validated by droplet digital PCR. PTEN and ARID1A immunohistochemistry was also performed for each specimen. Using the same protocol, I also analyzed hysterectomy and endometrial biopsy specimens obtained from cancer-free women.Results: Overall, we detected the presence of somatic alterations in 27.5% and 36.1% of IE and DE cases respectively. These events affected canonical components of RAS/MAPK or PI3K-Akt signaling pathways. Furthermore, over 50% of cancer-free women also harboured similar somatic alterations in their eutopic endometrial tissue. The presence of somatic cancer-drivers in the eutopic endometrium are likely regional and are correlated with age (p = 0.048).Conclusions: My findings are consistent with a uterine origin of endometriosis. Somatic cancer-driver alterations are commonly found in both endometriosis and the eutopic endometrium of cancer-free women and may reflect the accumulation of DNA damage over time. These somatic alterations alone are insufficient for malignant transformation and should be interpreted with caution in the early diagnosis of gynecologic malignancies given their common occurrence in cancer-free women.
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Publications
- Pathogenesis of bowel endometriosis (2020)
Best Practice & Research Clinical Obstetrics & Gynaecology, - Prognostic and theragnostic biomarkers in ovarian clear cell carcinoma. (2020)
- The molecular origin and taxonomy of mucinous ovarian carcinoma (2019)
Nature Communications, 10 (1) - Extrauterine high-grade serous carcinomas with bilateral adnexal involvement as the only two disease sites are clonal based on tp53 sequencing results: implications for biology, classification, and staging (2018)
Modern Pathology, 31 (4), 652--659 - You won't believe this old test … that does cheap single-cell mutation detection (2018)
The Journal of Pathology: Clinical Research, 4 (3), 149--153 - Genomic consequences of aberrant DNA repair mechanisms stratify ovarian cancer histotypes (2017)
Nature Genetics, 49 (6), 856--865 - Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition. (2015)
- Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden. (2015)
- Recurrent DICER1 Hotspot Mutations in Endometrial Tumours And Their Impact on MicroRNA Biogenesis. (2015)
- Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms. (2015)
- A current perspective on the pathological assessment of FOXL2 in adult-type granulosa cell tumours of the ovary. (2014)
- A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation. (2014)
- Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study. (2014)
- Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver. (2014)
- Harnessing the potential of lipid-based nanomedicines for type-specific ovarian cancer treatments. (2014)
- Accelerating type-specific ovarian carcinoma research: Calculator for Ovarian Subtype Prediction (COSP) is a reliable high-throughput tool for case review. (2013)
- Cancer-associated somatic DICER1 hotspot mutations cause defective miRNA processing and reverse-strand expression bias to predominantly mature 3p strands through loss of 5p strand cleavage. (2013)
- Correction: Type-Specific Cell Line Models for Type-Specific Ovarian Cancer Research. (2013)
- Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling. (2013)
- FOXL2 molecular testing in ovarian neoplasms: diagnostic approach and procedural guidelines. (2013)
- Hormone-receptor expression and ovarian cancer survival: an Ovarian Tumor Tissue Analysis consortium study. (2013)
- Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma. (2013)
- Molecular characterization of mucinous ovarian tumours supports a stratified treatment approach with HER2 targeting in 19% of carcinomas. (2013)
- Type-specific cell line models for type-specific ovarian cancer research. (2013)
- Benign serous ovarian tumour: a redefining moment? (2012)
- Cytokine gene expression signature in ovarian clear cell carcinoma. (2012)
- LRP1B deletion in high-grade serous ovarian cancers is associated with acquired chemotherapy resistance to liposomal doxorubicin. (2012)
- Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. (2012)
- The autophagy protein LC3A correlates with hypoxia and is a prognostic marker of patient survival in clear cell ovarian cancer. (2012)
- Clear cell carcinoma of the ovary: a report from the first Ovarian Clear Cell Symposium, June 24th, 2010. (2011)
- Copy number aberrations in benign serous ovarian tumors: a case for reclassification? (2011)
- Deregulation of MYCN, LIN28B and LET7 in a molecular subtype of aggressive high-grade serous ovarian cancers. (2011)
- IL6-STAT3-HIF signaling and therapeutic response to the angiogenesis inhibitor sunitinib in ovarian clear cell cancer. (2011)
- Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas. (2011)
- ARID1A mutations in endometriosis-associated ovarian carcinomas. (2010)
- Copy number analysis identifies novel interactions between genomic loci in ovarian cancer. (2010)
- Profiling the cancer genome. (2010)
- Are there any more ovarian tumor suppressor genes? A new perspective using ultra high-resolution copy number and loss of heterozygosity analysis. (2009)
- Mutation of ERBB2 provides a novel alternative mechanism for the ubiquitous activation of RAS-MAPK in ovarian serous low malignant potential tumors. (2008)
- The E3 ligase HACE1 is a critical chromosome 6q21 tumor suppressor involved in multiple cancers. (2007)
- Akt-mediated YB-1 phosphorylation activates translation of silent mRNA species. (2006)
- Differential expression of a novel ankyrin containing E3 ubiquitin-protein ligase, Hace1, in sporadic Wilms' tumor versus normal kidney. (2004)
Current Students & Alumni
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Member of G+PS
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Location
Vancouver General Hospital
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