This group is focusing on organ-on-a-chip (OOC) approaches to study diseases from causes, mechanisms, diagnostics and treatment with a specific interest in women’s health.
Bacterial vaginosis and the microbiome: Bacterial vaginosis (BV) is the most common vaginal infection in women of reproductive age. It has been shown to affect up to 50% of the female population in the developing world and up to 33% of women in the developed world. At present there is no curative treatment and recurrent infection is the norm. It is thought to contribute to miscarriage, premature delivery babies and pelvic inflammatory disease. It increases transmission of sexually transmitted infections, including human immunodeficiency virus (HIV), by two times. It is a disease that is poorly understood and no new therapeutics have been developed in the past 20 years that have shown any alteration in cure rates of BV.
Our current work is the development of an OOC system to mimic the lower female reproductive tract. This will create an in-vitro micro vaginal tissue which can mimic the in-vivo organ. In parallel we are conducting studies on bacteria associated with healthy microbiome including Lactobacillus spp. and those associated with BV including Gardnerella Vaginalis. The aim is to seed the bacterial species into the OOC model to give new insights into the disruption of lactobacillus spp. and formation of BV associated biofilms. This innovative approach will have utility in drug development and give researchers a new platform on which to dissect the aetiology of this complex and prevalent infection.
Breast Cancer: The alarming increase in the incidence of breast cancer worldwide cannot be explained solely by hereditary factors and strong evidence suggests that a substantial risk proportion can be attributed to extrinsic exposures. In fact, it has been estimated that 26.8% of all new breast cancers in the UK are related to lifestyle and environmental factors. However, still little is known about the contribution of environmental factors, such as exposures to environmental contaminants, to breast cancer risk. To date, no single risk factor has been shown to account for a substantial risk proportion, suggesting complex and multifactorial mechanisms for breast cancer aetiology. Taken together, this suggests that the overall breast cancer risk for women worldwide is still poorly understood and severely underestimated, and better estimations of the realistic risk are urgently needed, if we are to develop more robust preventative measures against the disease.
Our work aims at tackling these issues by studying the impact of chemicals and lifestyle factors on breast morphogenesis and carcinogenesis. For that, we employ innovative tools that integrate microfluidics and three dimensional (3D) in vitro breast cell co-culture systems with omics and network analyses.
Organ-on-a-Chip systems for EDCs: There is a growing concern to public health of the threat posed by endocrine disrupting chemicals (EDCs), environmental contaminants that interfere with the endocrine system and the normal hormone balance in the body. A large body of evidence links EDCs with health disorders in humans, such as breast cancer, implantation failure in pregnancy, polycystic ovary syndrome and endometriosis.
Ovarian Cancer: Ovarian cancer (OC) is the sixth most common cancer among females in the UK, accounting for 4% of all new cases of cancer in females. Every year over 7,000 women are diagnosed with ovarian cancer and It is projected that 10,501 new cases will be diagnosed in the UK in 2035. The total amount of ovarian cancer costs in the NHS is £460M per year, with the cost per patient being £65,740. Little is known about the potential role of the impact that EDCs have on ovarian cancer. Our work aims at developing a microfluidic 3D system to study the impact of EDCs on ovarian cancer initiation and progression.
Placental function and integrity: EDCs, such as the ubiquitous plasticiser Bisphenol A (BPA), have been associated with multiple effects on the female reproductive system, such as the onset of meiosis in oocytes, the generation of multi-oocyte follicles leading to ovulatory problems, pre-eclampsia, miscarriages and higher chances of implantation failure in the placenta. However, the impact of chemicals like BPA on placental development, placental function and reproductive outcome is still largely unknown. Our work focuses on developing and validating physiologically relevant 3D and microfluidics placental systems to investigate the impact of chemical exposures on placental integrity and function.
Organ-on-a-Chip Systems: Precise control of fluids and the environment surrounding microfluidic systems used within OOC is essential to ensure reliable, repeatable results are produced. The group is developing an automated system for the control of fluids, precise measurement of flow rates, pressure, pH, humidity and CO2 levels. Upstream loading can be conducted to allow for rapid assays such as live-dead bacterial staining. Downstream sampling can occur to enable selected molecules to be aliquoted off, for example to see if specific cytokines are present or allow gene expression analysis.