Projects

Chronic schistosomiasis (CS) is still a poorly recognized condition that can cause severe long-term complications of high cost for healthcare systems and decreased quality of life. Persistence of Schistosoma worms and eggs for decades induces chronic organ damage, inflammation and fibrosis resulting in renal failure, pulmonary hypertension, liver cirrhosis or stroke, among others. Albeit Praziquantel (PZQ) treatment is highly effective, the lack of specific diagnostic tools and accurate description of underlying pathological mechanisms precludes appropriate clinical management. Therefore, new diagnostics methods and deeper knowledge of underlying molecular mechanisms are urgently needed. Changes in blood inflammatory markers and/or serum metabolites could serve as indicators for disease burden and function as diagnostic biomarkers. Here, we aim to identify changes in the metabolome and/or inflammatory and immune-pathological mechanisms in a cohort of migrants affected of CS, providing insights into the causal molecular mechanisms associated to CS and offering tools for better disease management.

Immunotherapy has changed the treatment paradigm for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) in recent years. Although PD-L1 expression is a useful marker to predict the response to immunotherapy, it has important associated limitations, such as the limited response in tumors with overexpression of PD-L1, the heterogeneity in its expression, and the presence of immune escape mechanisms. This generates a need for biomarkers to select the best therapeutic option for each patient. The STAT3 pathway has been shown to participate in immune evasion through different mechanisms. The hypothesis of our work is that the expression levels of genes involved in the STAT3 pathway may play a predictive role in response to immunotherapy. In addition, the mRNA expression levels, as well as protein expression of these genes could change throughout the treatment and could be related to the prediction of efficacy of subsequent treatments. Our main objective is to analyze levels of gene expression of the STAT3 pathway activity in relation to the mutation and methylation of PTPRT, the overexpression of pSTAT3 and the expression levels of STAT3 mRNA as well as its relationship with the immunophenotype and different cytokines as predictors of response in a prospective pilot cohort of recurrent/metastatic HNSCC treated with chemoimmunotherapy or immunotherapy alone.

Schistosomiasis affects 250 million people worldwide, nearly 3% of the global population. In non-endemic countries like Catalonia, unrecognized schistosomiasis infection is highly prevalent among migrants. Prevalence studies indicate the presence of at least 30,000 infected individuals in Catalonia and more than 1.5 million in Europe. From an economic perspective, the costs to the Catalan healthcare system are extremely high, as chronic schistosomiasis leads to serious long-term complications such as infertility, chronic kidney failure, pulmonary hypertension, liver cirrhosis, and stroke. On the other hand, the treatment of choice for schistosomiasis, praziquantel (PZQ), is safe, low-cost, and highly effective. However, the lack of an efficient diagnostic tool prevents the establishment of a “test and treat” strategy, which would imply a net benefit estimated at around 25 million euros for a region like Catalonia, which hosts significant migrant populations from schistosomiasis-endemic countries.

Current diagnostic tools lack sensitivity, such as those based on microscopic observation of eggs in urine or stool, which are rarely present in long-term infections, or specificity, since serological techniques cannot distinguish between current and past infections. Our proposal aims to develop and validate a highly sensitive PCR-based diagnostic kit (HSqPCR) that becomes the universal standard method for diagnosing chronic schistosomiasis. Our tool addresses an unmet need between symptom-based clinical diagnosis and subsequent effective treatment and cure. Therefore, our diagnostic kit has the potential to change the landscape of schistosomiasis by (i) helping to identify easily treatable chronic infections in non-endemic countries like Catalonia and (ii) significantly reducing healthcare costs associated with long-term complications for the Catalan health system.

Schistosomiasis affects 250 million people worldwide, primarily in sub-Saharan Africa. Due to migration, it is estimated that around 15,000 people in the metropolitan area of Barcelona alone could be affected. Undiagnosed infection can lead to long-term complications such as genital schistosomiasis (GS), which carries a high cost for public health systems—costs that could be avoided by treating affected individuals. However, the WHO classifies it as a neglected disease, and most cases go undiagnosed and untreated, especially genital schistosomiasis, which is frequently misdiagnosed as a sexually transmitted infection (STI).

The aim of this project is to characterize GS from epidemiological, clinical, and molecular perspectives. To this end, we will estimate the prevalence of GS and characterize its immunopathological mechanisms. The project will involve a cross-sectional study of individuals originally from schistosomiasis-endemic areas who are long-term residents of the metropolitan area of Barcelona and present with symptoms compatible with the disease. Diagnosis of schistosomiasis and GS will be conducted using clinical, imaging, molecular, and inflammatory response assessments, analyzing plasma, semen, and cervicovaginal wash samples.

As a result, we will develop a screening strategy for GS, estimate its prevalence and associated risk factors, identify diagnostic biomarkers, and elucidate the underlying immunopathological mechanisms. The findings will provide the foundation for changing public health policy guidelines on schistosomiasis and improving the multiple associated dysfunctions, particularly those affecting sexual and reproductive health.

Immunotherapy has revolutionized the approach to treating recurrent and metastatic Head and Neck Squamous Cell Carcinoma (HNSCC), yet its effectiveness remains limited, benefiting only a small subset of patients. Given the pivotal role of STAT3 in immune signaling and preliminary results indicating STAT3 role in HNSCC prognosis, we aim to investigate the role of STAT3 and related pathways as predictive biomarkers to enhance treatment outcomes for HNSCC patients. To achieve this, we will comprehensively examine the critical components of STAT3 functionality through whole transcriptome analysis in a retrospective cohort of recurrent/metastatic (R/M) HNSCC patients. Additionally, in a prospective cohort of R/M HNSCC patients undergoing (chemo)immunotherapy, we will thoroughly analyze the tumor-immune crosstalk at various stages of treatment, both locally (at the single-cell level) and systemically, using immunophenotyping of immune cell populations and evaluation of inflammatory markers in blood. Furthermore, we will develop 3D heterotypic models resistant to immunotherapy, providing a versatile preclinical platform to explore novel alternative immunotherapeutic approaches applicable to various cancer types. Finally, by integrating multidimensional knowledge, we aim to refine the identification of blood-based biomarkers for practical application in clinical settings.

Immunotherapy has shown limited success in HR+ HER2- breast cancer, underscoring the need for better understanding of immune cell function in this subtype. This project aims to identify immune-derived biomarkers of response and develop improved therapeutic strategies, leveraging the immunomodulatory effects of CDK4/6 inhibitors. Using spatial transcriptomics and immune profiling in patient samples, we will study tumour-immune interactions and validate findings in a prospective cohort. Novel strategies will be tested in 3D immune-organoid models, providing preclinical proof of concept to guide future immunotherapies.