Studying the role of genomic cis-regulatory elements in the mechanisms underlying Mesial Temporal Lobe Epilepsy

• Grant number: 20/06168-4
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): October 01, 2020
• Effective date (End): August 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Iscia Teresinha Lopes Cendes
• Grantee: Jaqueline Cruz Geraldis
• Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology, AP.CEPID

Abstract

Temporal Lobe Epilepsy (TLE) is the most common form of epilepsy in adult patients. Mesial Temporal Lobe Epilepsy (MTLE) is one type of TLE characterized by the presence of an epileptic focus in the medial structures of the brain, such as the hippocampus, dentate gyrus, and amygdala. The typical histopathologic lesion found in most patients with MTLE is Hippocampus Sclerosis (HS) which is frequently associated with medically refractory seizures. For these patients, who do not respond to treatment with antiseizures medication, epilepsy surgery is an alternative treatment which can results in the good control of seizures, and the tissue resected can be used for molecular studies. Little is currently known about the role of cis-regulatory elements, present in the open chromatin regions, and how these regulate the biological multiples pathways leading to MTLE+HS. In this scenario, the main goal of our study is to identify and characterize the transcription factors binding sites in the entire genome in brain tissue from patients with MTLE+HS who underwent epilepsy surgery for the treatment of medically refractory seizures, also known as the genomic footprint, and compared it to control brain tissue from autopsy. Furthermore, we will determine the genomic footprint in different stages of the diseases seen in material from patients with different disease duration, and correlate to it with methylome and proteomics data, already obtained by our group (FAPESP # 2015/12960-4 and 2017/23954-0). We believe that our results will lead to a better panorama about gene expression cis-regulatory elements in MTLE+HS. In addition, we expect to identify regulatory elements and networks of molecular interactions which can be modulate in the future of part of the development of new therapeutic strategies to treat patients with refractory epilepsy. This study will be developed as part of the RIDC-BRAINN (www.brainn.org.br/en ), supported FAPESP (Process #2013/07559-3). (AU)