Immune signaling in neurodegenerative proteinopathies

Short Academic Biography of Cintia Roodveldt

Cintia Roodveldt is Assoc. Professor at the University of Seville (Dept. of Medical Biochemistry, Molecular Biology and Immunology), where she has been a faculty member since 2010. She is Principal Investigator at CABIMER-Center of Molecular Biology and Regenerative Medicine, Seville.
After graduating at the School of Biochemistry (1999, UNL, Argentina), she carried out her PhD studies (2000-2005) at The Weizmann Institute of Science (Israel, Supervisor: Dr. Dan S. Tawfik) and then performed a Postdoctoral stage (2006-2009) at Prof. Chris M. Dobson’s lab (University of Cambridge, UK). She received a number of fellowships and awards, including the Rodolfo May Fellowship (Weizmann Institute of Science/FGS), FEBS Long-Term Fellowship, FEBS Distinguished Young Investigator Award (2010), Clare Hall Research Fellow distinction (Cambridge) and Ramón y Cajal Programme (Spain).
Her research interests lie in the area of molecular mechanisms and immune signaling in neurodegenerative proteinopathies, including the identification of novel therapeutic targets that could lead to effective disease treatment.

Projects

Neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS), Parkinson’s and Alzheimer’s, are incurable and increasingly prevalent disorders characterized by progressive neuronal loss, the aggregation of specific proteins in the CNS, and the buildup of neuroinflammation. Indeed, it is currently thought that dysregulated immune responses involving uncontrolled microglia activation and peripheral immune imbalance play a major role in pathogenesis (Roodveldt et al., 2024). However, the mechanisms driving neurotoxic or neuroprotective immune processes in these highly complex disorders remain incompletely understood.
The aim of our research is to identify molecular mechanisms, signaling mediators and novel therapeutic targets related to relevant immune pathways involved in neurodegenerative diseases, particularly ALS and Parkinson.

Research Lines

a. Molecular mechanisms of immune responses in neurodegenerative diseases (ALS, Parkinson’s).

b. Role, mechanism and therapeutic potential of immune signaling kinases in ALS.

c. Transcriptional dynamics of immune cells in neurodegenerative and neuroinflammatory diseases.

Research Highlights

Amyotrophic lateral sclerosis (ALS) remains a devastating and incurable disease. Several studies have shown that microglia, the main immunocompetent cells in the CNS, become activated and neurotoxic, thereby contributing to motor neuron loss and disease onset and progression.
Our research work recently revealed the signaling kinase MOK (MAPK/MAK/MRK overlapping kinase), as a protein that mediates microglial inflammatory and type-IFN responses through a mechanism that directly implicates the epigenetic reader BRD4 (Pérez-Cabello, PNAS 2023).

Given that signaling kinases are known to be central immune mediators whose functions may be dysregulated in neuroinflammation-associated neurodegenerative diseases (Roodveldt et al., 2024; García-García et al., 2021) we sought to dissect the signaling pathways regulated by MOK in ALS-linked microglial responses. Apart from identifying BRD4 as a downstream target, we showed that MOK regulates both BRD4’s phosphorylated levels and chromatin-binding functions in the cell nucleus. Moreover, by applying proteomics and transcriptomics analyses, we revealed a number of key immune pathways that are activated upon immune stimulation in a MOK-dependent manner.

Remarkably, we also found that MOK is altered in spinal cord tissue from ALS patients and mouse models, particularly in microglial cells (Pérez-Cabello et al., 2023). Overall, our findings support a role for MOK in the pathogenic mechanisms of ALS and contributes to the search for novel and effective therapeutic targets against ALS and other neurodegenerative diseases.

For PhD STUDENT and POSTDOC applications, please send motivation letter and CV to cintia.roodveldt@cabimer.es

Funding (current and recent)