Centro Andaluz de Biología Molecular y Medicina Regenerativa

Immune signaling in neurodegenerative proteinopathies

/Research Groups/Immune signaling in neurodegenerative proteinopathies

Cintia Roodveldt, Ph.D.
Assoc. Professor (Profesor Titular), University of Seville, Spain
CABIMER-Andalusian Center for Molecular Biology & Regenerative Medicine.
“Immune signaling in neurodegenerative diseases” Lab

Background

My scientific career and interests have focused on molecular mechanisms of proteins and their role in pathophysiological processes. After my PhD studies (2000-2005, The Weizmann Institute of Science, Israel; Dr. Dan S. Tawfik) in the field of evolution of enzymes, I performed a 3 year-Postdoc (2006-2009) at Prof. Chris M. Dobson’s lab (University of Cambridge, UK). During that period, I dedicated my research to study the mechanisms and impact of molecular chaperones and their interaction with protein aggregates linked to neurodegenerative diseases.
In 2009 I joined Dr. David Pozo’s lab at CABIMER Center and started a new line of research on the effect of aggregating proteins in innate immunity in Parkinson. Since 2011, as ‘Miguel Servet’ (2011) and ‘Ramón y Cajal’ (2018) Researcher, I have led a research team and obtained a number of competitive grants by the Spanish Ministry of Science (2012, 2015, 2018, 2022) and Fundación Ramón Areces (2018). The aims of these projects have been to elucidate new molecular mechanisms underlying microglial responses in neurodegenerative proteinopathies and to explore novel immunotherapeutic strategies against these pathologies. I have published several articles as senior author and in collaboration, which have received >2700 cites (WoS).
I am Assoc. Professor (Prof. Titular) at the University of Seville and team leader at CABIMER. My current research lines focus on the “identification of novel molecular mechanisms, signalling kinases and therapeutic targets related to immune dysregulation in neurodegenerative diseases, particularly Parkinson and ALS”.

Contact
Tel. +34 954467841
email: cintia roodveldt@cabimer.es

Projects
Neurodegenerative diseases, including Parkinson’s, Alzheimer’s, and Amyotrophic Lateral Sclerosis (ALS/ELA), are incurable and increasingly prevalent disorders characterized by neuronal loss and the aberrant aggregation and deposition of specific proteins in certain areas of the brain. The underlying pathogenic mechanisms of these highly complex pathologies are still poorly understood, but dysregulated immune responses involving exacerbated neuroinflammation and peripheral immune imbalance, are currently thought to play a major role in pathogenesis.
The aim of my research is to identify novel molecular mechanisms, signaling kinases and therapeutic targets related to immune dysregulation in neurodegenerative diseases, particularly Parkinson and ALS.

Research Grants – Principal Investigator

  • 2023-26: ‘Plan Nacional I+D’, Spanish Ministry of Science (PID2022-140838OB-I00)
  • 2019-23: ‘Plan Nacional I+D’, Spanish Ministry of Science (RTI2018-098432-B-I00)
  • 2021-22: Proyectos I+D PAIDI, Junta de Andalucía (PY20_01097)
  • 2019-22: Proyectos ‘Ciencias de la Vida’, Fundación ‘Ramón Areces’, Spain
  • 2019-21: Programa FEDER-US, Junta de Andalucía (US-1265227)
  • 2015-18: RETOS-Colab., Spanish Ministry of Science-MINECO (RTC-2015-3309-1)
  • 2013-15: ‘Plan Nacional I+D’, Spanish Ministry of Science (SAF2012-39720)

ORCID
https://orcid.org/0000-0003-4124-8769
Google Scholar
https://scholar.google.com/citations?hl=es&user=P3wWFBgAAAAJ
Scopus
https://bibliometria.us.es/prisma/investigador/4979

Selected Publications:

  1. MAPK/MAK/MRK overlapping kinase (MOK) controls microglial inflammatory/type-I IFN responses via Brd4 and is involved in ALS. Pérez-Cabello JA, Silvera-Carrasco L et al., Tartaglia GG, Sawarkar R, García-Dominguez M, Pozo D, Roodveldt C**. Proc Natl Aacd Sci. USA. 120(28):e2302143120. 2023.
  2. Immune signalling kinases in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. García-García R, Martín-Herrero L, Blanca-Pariente L, Pérez-Cabello JA, Roodveldt C**. Int. J. Mol. Sci. 22(24):13280. 2021.
  3. Differential Interactome and Innate Immune Response Activation of Two Structurally Distinct Misfolded Protein Oligomers. Mannini B, Vecchi G, Labrador-Garrido A, Fabre B, Fani G, Franco JM, Lilley K, Pozo D, Vendruscolo M, Chiti F, Dobson CM, Roodveldt C**. ACS Chem Neurosci. 10(8):3464-3478. 2019.
  4. Immunization with α-synuclein/Grp94 reshapes peripheral immunity and suppresses microgliosis in a chronic Parkinsonism model. Villadiego J, Labrador-Garrido A, Muñoz-Franco J, Leal-Lasarte MM, De Genst EJ, Dobson CM, Pozo D, Toledo-Aral JJ, Roodveldt C**. Glia 66(1):191-205. 2018.
  5. Extracellular TDP-43 aggregates target MAPK/MAK/MRK (MOK) kinase and trigger caspase-3/IL-18 signaling in microglia. Leal-Lasarte MM, Franco JM, Labrador-Garrido A, Pozo D, Roodveldt C**. FASEB J. 31(7):2797-2816. 2017.
  6. The chaperonin CCT inhibits assembly of α-synuclein amyloid fibrils by a specific, conformation-dependent interaction. Sot B, Rubio-Muñoz A, Leal-Quintero A, Martinez-Sabando J, Marcilla M, Roodveldt C, Valpuesta JM. 2017. Sci. Rep. 7:40859. 2017.
  7. Chaperome screening leads to identification of Grp94/Gp96 and FKBP4/52 as modulators of the α-synuclein-elicited immune response. Labrador-Garrido A, Cejudo-Guillén M, Daturpalli S, Leal MM, Klippstein R, De Genst EJ, Dobson CM, Jackson SE, Pozo D, Roodveldt C**. FASEB J. 30(2):564-77. 2016.
  8. The ‘Omics’ of Amyotrophic Lateral Sclerosis. Caballero-Hernandez D, Toscano MG, Cejudo-Guillen M, Garcia-Martin ML, Lopez S, Franco JM, Quintana FJ, Roodveldt C, Pozo D. Trends Mol Med. 22(1):53-67. 2016.
  9. Structural characterization of toxic oligomers that are kinetically trapped during α-synuclein fibril formation. Chen SW, Drakulic S, Deas E, Ouberai M, Aprile FA, Arranz R, Ness S, Roodveldt C, et al., Dobson CM, Cremades N. Proc Natl Aacd Sci. USA 112(16):E1994-2003. 2015.
  10. α-Synuclein preconditioning of microglia strongly affects the response induced by TLR stimulation. Roodveldt C, Labrador A, Gonzalez-Rey E, Lachaud CC, Guilliams T et al., Dobson CM, Pozo D. PLoS One 8:e79160. 2013.
  11. Molecular mechanisms used by chaperones to reduce the toxicity of aberrant protein oligomers. Mannini B, Cascella R, Zampagni M, van Waarde-Verhagen M, Meehan S, Roodveldt C, et al., Chiti F. Proc Natl Aacd Sci. USA 109:12479-84. 2012.
  12. Chaperone proteostasis in Parkinson’s disease: molecular insights into the Hsp70/α-synuclein complex. Roodveldt C**, Bertoncini CW, Andersson A, van der Goot AT, Hsu ST, Fernandez-Montesinos R, de Jong J, van Ham TJ, Nollen EA, Pozo D, Christodoulou C, Dobson CM**. EMBO J. 28, 3758-70. 12/1. 2009.
  13. Shared promiscuous activities and evolutionary features in various members of the amidohydrolase superfamily. Roodveldt C & Tawfik DS. Biochemistry. 44, 12728-12736. 2005.
  14. The ‘evolvability’ of promiscuous protein functions. Aharoni A, Gaidukov L#, Khersonsky O, McQ Gould S#, Roodveldt C# & Tawfik DS. #Equally contributing authors. Nat. Genet. 37, 73-76. 2005.

Group leader:
PhD students:
  • Raquel García García
  • Sabine Vernon