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 both graduate students and post-doctoral fellows to join a dynamic and growing research team. If you are interested in joining my team please read and respond to the Ideal Applicant Profile below.
Graduate Student projects include research into genomic and microenvironment links between chronic cancer precursors (endometriosis and/or uterine hyperplasia) and frank carcinomas that arise from these precursor lesions (endometrial carcinoma, clear cell or endometrioid ovarian carcinoma).
Post Doctoral project will involve the evaluation of somatic cancer driver mutations in non-cancer endometriosis and will require knowledge of sequencing methods (NGS and others), biostatistics, and the ability to use bioinformatics tools. PDF may apply to the following directly via UBC Workday:
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. (For clarification: my research does not involve assisted reproductive technologies, fertility, or midwifery.)
Please note that only qualified candidates will be contacted following applications.
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.
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. Please also refer to the requirements set out by the WACH+ program for additional information https://wach.med.ubc.ca
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.
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.
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.