Clinical Research Directory

How Gut Health Affects Immune Responses to the Oral Rotavirus Vaccine in Adults in Zambia

The Rotavirus SpatioTrasncriptomics (Rota-Omics) study is a multidisciplinary research project aimed at understanding why oral rotavirus vaccines perform less effectively in some low- and middle-income countries, including Zambia. Rotavirus remains one of the leading causes of severe diarrheal disease in infants and young children worldwide, despite the widespread introduction of vaccines such as Rotarix® and Rotavac®. Although these vaccines have greatly reduced childhood deaths in many countries, vaccine effectiveness is often lower in settings where the burden of disease is highest. Understanding the reasons behind this reduced protection is critical for improving child health globally. A major focus of the study is Environmental Enteropathy (EE), also known as Environmental Enteric Dysfunction (EED), a chronic inflammatory condition of the small intestine that is common in low-resource settings. EE is associated with damage to the intestinal lining, chronic immune activation, poor nutrient absorption, and impaired gut barrier function. These changes are thought to interfere with the body's ability to respond effectively to oral vaccines, which rely on strong intestinal immune responses. The RotaOmics study uses a systems biology approach to investigate how the immune system, gut microbiome, nutrition, and intestinal inflammation interact to influence rotavirus vaccine responses. The term "omics" refers to advanced technologies that allow researchers to study genes, proteins, microbes, and other biological processes at a large scale. By combining these approaches, the study aims to identify biological markers and immune pathways associated with strong or weak vaccine responses. The study involves the collection of samples such as blood, stool, saliva, and breast milk from mothers and infants at different time points before and after vaccination. These samples are analysed using laboratory methods including antibody testing, molecular pathogen detection, microbiome sequencing, and immune profiling. The study also evaluates markers of gut inflammation and intestinal health. One important goal of the project is to identify correlates of protection, which are measurable biological indicators that predict whether a vaccine is likely to protect against disease. Identifying these markers could help guide the development of improved vaccines or supportive interventions to enhance vaccine performance in vulnerable populations. The study also contributes to a broader understanding of mucosal immunity, which refers to immune responses occurring in the gastrointestinal tract. Since many enteric infections begin in the gut, understanding intestinal immune function is important not only for rotavirus vaccines but also for other oral vaccines and diarrheal diseases. In addition to its scientific objectives, RotaOmics includes a strong capacity-building component. The project supports training for local scientists, clinicians, and laboratory personnel in areas such as molecular biology, immunology, genomics, bioinformatics, and data analysis. By strengthening local research expertise and infrastructure, the study aims to support long-term scientific development and improve regional capacity for infectious disease research and outbreak response. Overall, the RotaOmics study seeks to generate new insights into why oral rotavirus vaccines underperform in some settings and to identify strategies that may improve vaccine effectiveness and child health outcomes in Zambia and similar regions worldwide.

Epigenomic and Transcriptomic Analysis in BRCA Mutated Carriers With and Without Serous Tubal Intraepithelial Carcinoma

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy and is typically diagnosed at an advanced stage, limiting opportunities for early detection and intervention. Women carrying germline pathogenic variants in BRCA1 or BRCA2 have a substantially increased lifetime risk of developing HGSOC compared with the general population. Risk-reducing salpingo-oophorectomy (RRSO), currently the most effective preventive strategy for these women, has enabled the identification of isolated serous tubal intraepithelial carcinomas (STICs), which are now recognized as key precursor lesions in the serous carcinogenic pathway. Emerging evidence indicates that transcriptomic and epigenetic alterations associated with BRCA-related carcinogenesis may be present even in histologically normal tissues, suggesting that molecular changes precede the development of invasive disease. Characterizing these early alterations may improve understanding of ovarian cancer initiation and support the identification of biomarkers for risk assessment and early detection. Previous work demonstrated the feasibility and cost-effectiveness of a radiogenomic, ultrasound-based model capable of predicting germline BRCA1/2 status from imaging features of morphologically normal ovaries. However, the biological basis underlying these imaging signatures remains unclear. Defining the molecular differences between BRCA carriers and non-carriers may provide a mechanistic rationale for these radiogenomic findings and support future validation of imaging-based prediction models. This exploratory translational study will investigate transcriptomic and DNA methylation profiles in ovarian tissue samples from BRCA1/2 mutation carriers and BRCA wild-type controls. Three groups will be included: BRCA carriers undergoing RRSO without evidence of STIC lesions, BRCA carriers undergoing RRSO with unilateral STIC lesions and paired ovarian samples available, and presumed BRCA wild-type women undergoing adnexal surgery for benign gynecologic indications. The first objective is to identify baseline transcriptomic and epigenomic signatures that distinguish healthy ovaries from BRCA carriers and BRCA wild-type controls, thereby defining molecular features associated with hereditary predisposition. The second objective is to characterize molecular alterations associated with STIC lesions through comparison of STIC-containing ovarian samples with paired contralateral non-STIC ovarian tissue from the same BRCA carrier, allowing identification of lesion-associated changes while minimizing inter-individual variability. The third objective is to compare STIC-containing ovarian samples with healthy ovarian tissue from BRCA carrier controls to identify pathways involved in the earliest stages of serous tumorigenesis and the transition from genetic susceptibility to precursor lesion development. A total of 30 women will be included: 10 BRCA carriers without STIC lesions, 10 BRCA carriers with unilateral STIC lesions, and 10 BRCA wild-type controls. Integrated transcriptomic and DNA methylation analyses will be performed on available ovarian tissue samples. The resulting data are expected to improve understanding of the molecular landscape associated with BRCA-related ovarian cancer predisposition and early carcinogenesis, provide biological support for radiogenomic prediction models, and identify candidate biomarkers for future prevention and early-detection strategies.

Molecular Profiling of MRI-PSMA PET Discordance in Prostate Cancer

MRI and PSMA-PET are highly sensitive imaging tools for prostate cancer, yet they often detect different lesions. These discordant findings pose clinical uncertainty because their biological significance is unclear. This project aims to molecularly characterize MRI-PSMA PET discordant lesions using high-quality biobanked samples from patients enrolled in an institutional study (NCT06187870). By integrating imaging and molecular data, the study will clarify whether these lesions represent indolent disease, aggressive subclones, or biologically distinct entities, and will assess their clinical implications.

Augmented Response of Volatile Biomarkers in Assessment of Oesophagogastric Cancer (AROMA 1 / BIORESOURCE)

Cancer of the stomach and oesophagus is among the world's top five cancers. Survival rates are very poor as the disease presents late and early symptoms are non-specific. The study team has developed a non-invasive test for cancers of the stomach and oesophagus based on the detection of volatile organic compounds in exhaled breath. These compounds are known to be produced by both cancers as well as cancer associated bacteria within the gut. The proposed innovation is to improve the accuracy of this test by investigating whether simple metabolic substrates can increase the production of these volatile organic compounds by both the tumour and its associated bacteria.

Study of the Relationship Between Clinical, Imaging and Biological Data in Patients With Squamous Cell Carcinoma of the Tongue

Squamous cell carcinoma (SCC) could be a very aggressive cancer and has a bad prognosis if not detected early and thus is associated with high mortality. The development of simple and reliable biomarkers for the early detection of SCC is one of the solutions to better diagnose, treat these tumors, evaluate and monitor treatments, and hence reduce mortality. In a previous work, the investigators demonstrated the ability of Proton Magnetic resonance spectroscopy (1H-MRS) to non-invasively assess spectroscopic and metabolic profiles of tongue tissue in healthy subjects. In the present work, the investigators challenge the use of in-vivo 1H-MRS as a potential method for non-invasive metabolic monitoring of patients with squamous cell carcinoma of the tongue undergoing therapy. Thus the main objective is to study the spectroscopic and metabolic differences, e.g. including variation in the metabolite TMA-Cho (trimethylamine-choline), of tongue tissue between healthy subjects and in patients with squamous cell carcinoma of the tongue, before and after surgery.