Molecular mechanisms involved in the development of post-Chikungunya Chronic Inflammatory Joint Disease

• Grant number: 22/11933-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2023
• End date: November 21, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Ester Cerdeira Sabino
• Grantee: Mariana Severo Ramundo
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/14389-0 - Brazil-UK Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE), AP.TEM

Abstract

Chikungunya fever (CF) remains an important public health problem in Brazil. Although most patients have symptoms resolution in the acute phase of the disease, 25-50% of cases progress to post-Chikungunya Chronic Inflammatory Joint Disease (pCHIKV-CIJD, post-Chikungunya Chronic Inflammatory Joint Disease), impacting directly on the quality of life of these patients. Despite causing epidemics of large proportions, data on the biology of the disease remain incipient and to date there are no specific treatments that can mitigate or eliminate the impacts of pCHIKV-CIJD. Thus, our research group has been developing studies to fill the existing knowledge gap. In this sense, this postdoctoral project proposal aims to study the molecular mechanisms and metabolic pathways involved in the early progression of the acute disease to pCHIKV-CIJD, seeking to find molecular signatures that may be useful for drug repositioning in order to mitigate or eliminate the risk of the disease in its early stages, culminating in a better quality of life for patients. To achieve this objective, we will use total RNA and microRNA sequencing data already obtained in a previous project and apply machine learning and other bioinformatics tools such as Gene Set Enrichment Analysis (GSEA) and co-expression modules to obtain the gene signatures associated with chronic disease. To verify if there are drugs available that act on these pathways, we will use the Drug Gene Interaction Database. This study is low risk, since the data that will be analyzed are already collected and available and will be carried out in collaboration with Dr Helder Nakaya, reference in Systems Biology having numerous published studies in the area, including arboviruses.