1st Year Research Student Talks (Chengchen Duan, Toluwalase Awoyemi, Lindsay Baxter, Danielle Perro and Shiyan Tang)
Chengchen Duan: “Dual Functional Polymer-Lipid Hybrid Nanoparticles for Gene Editing Cancer Therapies and Real-Time Evaluation of Therapeutic Effects.”

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma and is extremely aggressive and highly malignant. The majority of cases occur in children, and most commonly appear in the arms or legs. Currently RMS is treated with aggressive chemotherapy, as well as surgery and/or radiation in many cases. The aggressive treatments often cause long term after effects, and can even cause permanent life-altering disabilities. Alternative treatment modalities are urgently needed. In this project, we aim to fabricate a siRNA nano-delivery system using polymer-lipid hybrid nanoparticles (PLN). The PLN will be pH activatable such that the cargo is only released in the tumour cells which have lowered pH. Compared with traditional nanosystems, PLNs could provide better protection of siRNA and enable higher bio-distribution in tumour tissues. Targetting will be achieved through DNA aptamer-based surface modification, and will incorporate a NIR label. This NIR-DNA aptamer will enable real-time evaluating of the therapeutic effect. Furthermore, due to the penetrating depth of NIR light, the nanoparticles can be monitored non-invasively. This project will set up the foundation of an efficient dual functional nanosystem which could be clinically applied in the future.

Toluwalase Awoyemi: “Placenta derived biomarkers of pregnancy disorders.”

The Placenta is a remarkable organ that performs several functions vital for the survival of the fetus: hormone synthesis, gaseous exchange, metabolism etc. Its presence is pivotal for the development of a normal pregnancy. Similarly, abnormal placentation leads to disease states. Despite increasing interest in the role of placenta in normal and abnormal pregnancy e.g. Pre-eclampsia and preterm labour.  My research is attempting to dissect molecular mechanisms of both these conditions. For preeclampsia (a common cause of maternal and fetal morbidity and mortality) with a global prevalence of 2-8%, the anti-angiogenic molecule sFlt-1 has been shown to play an important role. The sFlt-1 is both free and bound to placental extracellular vesicles, which are released from the surface of the placenta into the maternal circulation. My research hopes to elucidate what additional roles vesicle bound sflt-1 may play in pre-eclampsia. For preterm birth, infection has long been said to be a significant cause of the condition. In order to dissect this, I will challenge the sterile womb hypothesis,  and determine the prevalence of pathogens in both term and pre-term placentas and the consequence of dysbiosis on the timing of delivery.

Lindsay Baxter: “The effects of advanced maternal ageing on oocyte quality and its implications for early pregnancy failure, using a horse model.”

The objectives of my project is to investigate and modify age-related changes in oocyte development and the effect on early pregnancy failure using a horse model. Advanced maternal age predisposes pregnancy loss in both humans and horses, and although oocyte quality is the primary factor in both species, the exact causes of the decline have not been determined. The first objective will be to define age-related changes in the horse oocyte transcriptome using single oocyte RNAseq. I will compare oocytes and cumulus cells from young and old horses, to determine age-related changes. Since egg development requires complex bidirectional support from the surrounding somatic cells, for the second objective, we will determine if the transcriptome of eggs from older mares can be ‘improved’ by growing them with somatic cells from younger mares: this technique is known as ovary reaggregation. From these rescue experiments we will determine if oocytes successfully reaggregated using PGCs from aged mare ovaries are altered depending on whether the oocyte was grown with younger somatic cells. The third objective will be to determine if the ‘modified’ eggs developed in vitro can develop in vivo in the horse.

Danielle Perro: “Characterising extracellular vesicles in women with endometriosis-associated pain.”

Endometriosis is a chronic inflammatory disease characterized by the inappropriate growth of endometrium-like tissue outside of the uterine cavity. This disease affects approximately 10% of women of reproductive age, and many of these women experience disease-associated pain. Very little is known about the underlying pain mechanisms and phenotypes. In other inflammatory diseases such as rheumatoid arthritis (RA), extracellular vesicles (EV) have been shown to play a role in RA associated pain and inflammation. Due to the comorbid nature of RA and endometriosis, there are grounds for exploring the role, if any, of EV’s in endometriosis-associated pain. The aim of this project is to isolate and characterize EV in women with different endometriosis-associated pain phenotypes. In the literature, there are established protocols for the isolation and characterization of EV which have been optimized for peripheral blood samples. So, initially our study will aim to identify distinct EV populations in the plasma of women with endometriosis. Additionally, we will investigate whether these EV populations are reflective of the woman’s disease-associated pain profile by identifying their cellular origin and variation in concentration between women with different pain phenotypes. The findings of this work may set the groundwork for a minimally invasive, objective tool that allows researchers and clinicians to simply understand a woman’s pain experience.

Shiyan Tang: “Fertility preservation in pre-pubertal boys with cancer: Developing a three-dimensional scaffolding system to encourage in vitro spermatogenesis in frozen/thawed testicular samples.”

Annually, around 2000 new cases of childhood cancer are diagnosed in the UK. While current cancer treatments have led to an overall increase in survival rate, the use of aggressive chemo- or radio-therapies frequently causes irreparable damage to the pre-pubertal gonad, thus resulting in sterility. Since the production of functional sperm from spermatogonial stem cells (SSCs) in the testis only begins at puberty, it is not possible to cryopreserve mature sperm from pre-pubertal boys, as would be the case in adult males. Consequently, the cryopreservation of pre-pubertal testicular tissue, harvested prior to the initiation of cancer treatment, for future re-implantation or derivation of spermatogenesis in vitro, has been proposed as a possible way to restore fertility in childhood cancer survivors. However, more studies are urgently needed to explore in vitro methods to protect, culture and enhance the development of immature testicular tissue and to encourage the synthesis of mature fertilization-competent sperm. The project aims to develop 3D scaffolding systems to encourage in vitro spermatogenesis in frozen/thawed testicular tissue.
Date: 5 March 2019, 13:00 (Tuesday, 8th week, Hilary 2019)
Venue: John Radcliffe Women's Centre, Headington OX3 9DU
Venue Details: The Anne Anderson Lecture Theatre, Level 3
Speakers: Speaker to be announced
Organising department: Nuffield Department of Women's and Reproductive Health
Organiser: Dr Jen Southcombe (University of Oxford)
Booking required?: Not required
Audience: Members of the University only
Editor: Susie Barber