Intrinsic muscle abnormalities in Amyotrophic Lateral Sclerosis
Sonia Alonso Martin
Group Leader of “Muscle Stem Cells & Regenerative Medicine” Lab within the Neuromuscular Diseases Group (Neurosciences Area) at BIODONOSTIA HRI (Donostia/San Sebastián, Spain). Research Fellow – Gipuzkoa Fellows Program for Talent Attraction and Retention.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the death of motor neurons (MN) and muscle atrophy. Classically, muscle atrophy has been assumed to arise from MN denervation, but recent research has proposed that this process may be muscle-autonomous. On the other hand, there is a growing body of evidence supporting that ALS presents systemic metabolic disturbances. The facts that insulin resistance and type I diabetes are risk factors in ALS, and that glycolytic fast fibers are affected early in the process of MN degeneration, whereas the most, aerobic ones (extraocular), are spared, devise a range of evidences to postulate that altered energy production from glucose may be an early pathogenic event in ALS. With the aim to address the hypothesis that there are intrinsic abnormalities in skeletal muscle linked to ALS pathology, we cultured primary myoblasts from ALS patients and performed an array of biochemical and functional studies. Patients´ primary myoblasts displayed alterations in the nuclear localization of TDP-43, consistent repression of glycolysis and aberrant myogenesis. Furthermore, we induced silencing of TDP-43 and FUS in control human primary myoblasts to verify whether their loss of function may phenocopy such abnormalities. Indeed, TDP-43- FUS-knockdown myoblasts showed defects in the glycolytic capacity and, more importantly, dramatic defects in the myogenic process.
Sonia Alonso-Martín: Group Leader of “Muscle Stem Cells & Regenerative Medicine” Lab within the Neuromuscular Diseases Group (Neurosciences Area) at BIODONOSTIA HRI (Donostia/San Sebastián, Spain). Research Fellow – Gipuzkoa Fellows Program for Talent Attraction and Retention.
Sonia Alonso-Martin is a highly qualified scientist, with an outstanding background in Myology, Mouse Molecular Genetics and Gene Regulation, and broad knowledge in Transcriptomics and Stem Cell Biology.
She is a renowned researcher in the skeletal muscle stem cell field, in which she contributed with high impact outcomes, including relevant international collaborations. She is author of 23 research papers and more than 50 scientific communications.
After completing a successful PhD in Madrid (CIB-CSIC) on ESC manipulation to generate new animal models for platelet-associated diseases, pioneer in her institution, she moved to France for a post-doctorate in F. Relaix lab (Paris & Créteil).
Remarkably, during her post-doctoral research works, she performed a stem cell ontology, from development to aged mice, identifying molecular pathways involved in the emergence of postnatal muscle stem cells in vertebrates, as well as the genetic changes associated with the stemness capacity of these cells. Back in Spain in 2016, she joined Pura Muñoz lab (CNIC-Madrid and UPF-Barcelona), where she focused on stem cell heterogeneity and aging, successfully publishing as first author in prestigious Nature Cell Biology journal.
In 2019, she has been awarded the “Gipuzkoa Fellows Program for Talent Attraction and Retention” which allowed her to start her own research group within the Neuroscience Department at Biodonostia HRI. Relying on her expertise in muscle biology, her group is unravelling the complexity of muscle dystrophies and motor neuron disorders, specially ALS, developing a total innovative approach for a better understanding of the different neurodegenerative diseases, including sarcopenia due to disuse or aging.
She is member of CIBERNED, the Network Center for Biomedical Research in Neurodegenerative Diseases; she is Review Editor for Frontiers in Cell and Developmental Biology; and serves as reviewer for different scientific journals. She is scientific evaluator and/or advisor for different committees and institutions such as FWO (Research Foundation – Flanders) and the Spanish National Research Agency (AEI).
More information on Sonia Alonso Martin ‘s Linkedin webpage