Understanding the pathophysiology of Keutel Syndrome: A path towards cure

• Applicant: Professorin Magali Cucchiarini, Ph.D.
• Subject Area: Pathology ; Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 441083034

• Final Report Year: 2024

Final Report Abstract

The currently funded project allowed to successfully generate several new findings in vitro and in relevant models in vivo in order to advance the understanding of the pathophysiology of the Keutel Syndrome via a collaborative, multidisciplinary effort allowing to define potential new targets for KS therapy, including via gene-based treatments. Dissemination of the generated data at national and international conferences highlights the significance and potential impact of the research in the scientific community.

Publications

• Editorial: Ectopic Mineralization of Tissues: Mechanisms, Risk Factors, Diseases, and Prevention. Frontiers in Cell and Developmental Biology, 9.
  Kempf, Hervé; Komarova, Svetlana & Murshed, Monzur
  
• Elastin calcification in in vitro models and its prevention by MGP’s N-terminal peptide. Journal of Structural Biology, 213(1), 107637.
  Parashar, Abhinav; Gourgas, Ophélie; Lau, Kirk; Li, Jingjing; Muiznieks, Lisa; Sharpe, Simon; Davis, Elaine; Cerruti, Marta & Murshed, Monzur
  
• Keutel Syndrome, a Review of 50 Years of Literature. Frontiers in Cell and Developmental Biology, 9.
  Cancela, M. Leonor; Laizé, Vincent; Conceição, Natércia; Kempf, Hervé & Murshed, Monzur
  
• Prevention of Arterial Elastocalcinosis: Differential Roles of the Conserved Glutamic Acid and Serine Residues of Matrix Gla Protein. Arteriosclerosis, Thrombosis, and Vascular Biology, 42(6).
  Parashar, Abhinav; Bak, Kyoungmi & Murshed, Monzur
  
• Specific heterozygous variants in MGP lead to endoplasmic reticulum stress and cause spondyloepiphyseal dysplasia. Nature Communications, 14(1).
  Gourgas, Ophélie; Lemire, Gabrielle; Eaton, Alison J.; Alshahrani, Sultanah; Duker, Angela L.; Li, Jingjing; Carroll, Ricki S.; Mackenzie, Stuart; Nikkel, Sarah M.; Bober, Michael B.; Boycott, Kym M. & Murshed, Monzur
  
• Zebrafish Models to Study Ectopic Calcification and Calcium-Associated Pathologies. International Journal of Molecular Sciences, 24(4), 3366.
  Santos, João M. A.; Laizé, Vincent; Gavaia, Paulo J.; Conceição, Natércia & Cancela, M. Leonor
  
• Author Correction: Specific heterozygous variants in MGP lead to endoplasmic reticulum stress and cause spondyloepiphyseal dysplasia. Nature Communications, 15(1).
  Gourgas, Ophélie; Lemire, Gabrielle; Eaton, Alison J.; Alshahrani, Sultanah; Duker, Angela L.; Li, Jingjing; Carroll, Ricki S.; Mackenzie, Stuart; Nikkel, Sarah M.; Bober, Michael B.; Boycott, Kym M. & Murshed, Monzur
  
• rAAV-mediated overexpression of Gla-deficient mutant Matrix Gla Protein limits its potential to inhibit mineralization in SaOS2 cells. In M. Aureliano, M. Simão, B. I. Ferreira, A. L. Coelho, S. Simão, A. Costa, C. Antunes, L. Cancela (Eds.), Lifespan, Health and Metabolic Diseases. Book of abstracts, IX Clinical Biochemistry Workshop, 2024, 64-64. UAlg Editora
  Geraldo, L., Miguel, L., Conceição, N., Santos, J., Venkatesan, J. K., Cucchiarini, M., Simão, M. & Cancela, M. L.