Doctor of Philosophy in Reproductive and Developmental Sciences (PhD)
Educational videos on the pathophysiology of sexual pain in women with endometriosis
I am currently recruiting graduate students to join a dynamic and growing research team. If you are interested in joining my team please read and respond to the opportunities.
(N03.2023) Graduate Students (MSc/PhD) – to take on genomic and biomarker centric research on endometriosis. Optimal candidates will have experience with PCR-based methods, sequencing, next-generation sequencing, and/or IHC. Candidates should have a working knowledge of female anatomy and physiology, especially around uterine and ovarian biology. Experience with histopathology and recognizing different cell types under a microscope is highly beneficial. Candidates should have strong grades in statistics. Candidates must have a strong work ethic, and be able to work independently (problem solve) and be effective in a dynamic team environment.
(PA01.2023) Graduate Students (MSc) – to take on a novel project examining molecular changes associated with uterine aging. The candidate should have experience with PCR-based methods, sequencing, and next-generation sequencing. Knowledge of female reproductive biology is an asset as is familiarity with medical/pathology nomenclature and terminology. In addition to molecular analysis, the candidate will work with other groups to analyze health care records and health services utilization. Candidates should have strong grades in statistics. Candidates must have a strong work ethic, and be able to work independently (problem solve) and be effective in a dynamic team environment.
Applications that are not relevant to our research group, and applicants that do not apply for the advertised positions, may not receive a reply.
For graduate trainee applicants please keep in mind application deadlines are many months in advance of study start dates. See more information at the Women+ and Children’s Health Sciences (WACH) program website https://wach.med.ubc.ca/
Prospective students and postdocs should send their applications along with their research interests, CV and transcript with at least their last three years of academic performance. Please only send an application if your research interests align to current projects in the lab. Please do not send applications for projects unrelated to listed laboratory projects.
Candidates should work well both within a team environment and independently, be able to collaborate, mentor, and supervise other junior trainees. Candidates that are able to bring new knowledge and application to the group are desirable.
In the context of our research programs candidates should have skill and experience with molecular, immunohistochemical, PCR, and sequencing/NGS based techniques (wet-lab, hands-on experience required). Optimal candidates may also have experience with one or more of: animal models, biostatics, analysis of NGS datasets, microbiome research, proteomics, and/or epigenomics. We are primarily a wet lab research group and thus are unable to accommodate candidates whishing remote work/study.
[Not currently recruiting] Post-doctoral candidates should have at minimum a PhD with experience in gynecological cancer research and/or uterine-derived pathologies (e.g. hyperplasia, endometriosis, and similar). Knowledge in biomarker discovery and development including outcomes analysis is beneficial. Experience using bioinformatics/sequencing-based bioinformatics tools is a major asset.
Graduate studies candidates should be interested in wet bench research including cell culture, animal models, biomarker discovery and validation. Some experience with techniques such as cell culture, PCR, immunohistochemistry, and basic biostatistics is an asset. Applicants should have first-class academic average (>80%) and be competitive for external funding (e.g. from CIHR). Graduate candidates will not be accepted directly into a PhD stream but rather are expected to enter an MSc stream and will be provided an option to transfer to PhD depending on project, funding, and performance.
Interested candidates: please send your CV, transcript (minimum last 3 years of academic grades), and statement of research interest using the "request for supervisor" function on this page or links to specific job postings (see above). Incomplete applications will not be considered. Only qualified and competitive candidates will be contacted for interviews or discussion.
G+PS regularly provides virtual sessions that focus on admission requirements and procedures and tips how to improve your application.
These videos contain some general advice from faculty across UBC on finding and reaching out to a potential thesis supervisor.
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
Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
Endometriosis is a gynaecological condition that affects 10-15% of people with a uterus and is defined when endometrial-like tissue forms lesions in ectopic environments, most commonly within the pelvic cavity [1, 2]. The reflux of eutopic endometrium into the pelvic cavity, via retrograde menstruation, is the most common explanation for endometriosis development; however, more factors (such as gene expression alterations and immune dysregulation) are likely to contribute to the development of endometriotic lesions [3, 4]. It has recently been discovered that patients with deep infiltrating endometriosis, an invasive subtype of endometriosis, tend to have a mutation in KRAS codon 12 confined to the epithelium of the endometriosis lesions and within the eutopic endometrium . To achieve a deeper understanding of the roles of the KRAS mutation in the development of endometriosis, this thesis has two aims: 1) compare the morphology and expression profiles between Kras-mutant and Kras-wildtype eutopic endometrium and 2) develop a novel mouse model for endometriosis with epithelium-restricted Kras mutation. In Aim 1, I found significant downregulation of genes related to the extracellular matrix and upregulation of genes involved in inflammation in Kras-mutant compared to Kras-wildtype uterine tissue. Furthermore, differential regulation of genes involved in epithelial-mesenchymal transition, decidualization, and ferroptosis were also identified. The differential expression of various genes between Kras-mutant and wildtype uterine tissue may partially explain the development of endometriosis and associated symptoms. Aim 2 investigates this potential role of Kras mutations in the development of endometriosis; however, lesion establishment was unsuccessful. Nonetheless, this model provided a good framework to inform the development of future endometriosis mouse models. The characterization of differentially regulated genes between mutated and wildtype endometrial tissue could have large implications in future preclinical studies that focus on the role of somatic mutations in the proliferation and growth of the invasive tissue, with the end goal of developing novel personalized treatments suitable for patients affected by endometriosis.
Representing approximately 5% of all epithelial ovarian cancers, low-grade serous ovarian carcinoma (LGSC) is a rare histotype with unique genetic, molecular, and pathological features. LGSC patients are often detected at an advanced stage and respond poorly to platinum-based chemotherapy. Therefore, targeted therapies focused on exploiting oncogenic dependencies have homed in on the RAS/RAF/MEK/ERK (MAPK) signaling pathway, due to frequent activating MAPK mutations in LGSC tumours. Trials using MEK inhibitors (MEKi) have seen a modest increase in patient response, however, no cellular markers that distinguish MEKi response have been identified. This research aimed to discover and target protein markers of MEKi response by analyzing the global proteome of in-vitro cell lines previously established from patient samples through mass spectrometric analyses. 95 proteins were identified as being significantly differentially expressed between four MEKi sensitive and three MEKi resistant LGSC cell lines. Nine of these proteins were selected for further analysis, with the differentially protein expression of five markers being successfully validated. One of these confirmed markers, EGFR (a common driver of oncogenesis), was selected for paired inhibition with MEK using a combination of small molecule inhibitors specific for MEK and EGFR to induce cellular apoptosis in MEKi resistant LGSC lines. Four de novo and three acquired MEKi resistant LGSC cell lines were treated with a combination of erlotinib (EGFRi) and either selumetinib or trametinib (MEKi’s). Cellular response was analyzed by live-cell imaging, cell proliferation, and viability assays. A linear mixed effects model and drug synergism analysis was implemented to evaluate the efficacy of MEKi and EGFRi in combination. In the four de novo resistant LGSC lines, the drug combination induced complete cell death in two lines and demonstrated a degree of drug synergism in another. In the acquired MEKi resistance setting however, none of the cell lines responded to dual EGFR and MEK inhibition. Therefore, the combined inhibition of EGFR and MEK may represent a potential therapy for overcoming de novo MEKi resistance in LGSC, but not as a strategy for combatting acquired MEKi resistance.
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.