Excited to share that Xiao(Andy), David and Jik have led a new study published in Cell:
Read the paper here: 🧪 “Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates”
They even have a visual summary of this study: Watch the Video here
This study uncovers how stress granules can promote pathological aggregation of TDP-43 — a key driver of ALS and FTD. Xiao identified a two-step mechanism: local concentration of TDP-43 inside stress granules, followed by oxidation-induced intra-condensate demixing , which triggers pathological aggregation. Importantly, blocking this demixing prevents TDP-43 aggregation in motor neurons, pointing to a potential therapeutic target. Here’s a closer look at the authors behind this work from the Hyman Lab.
🔬 About Xiao Yan
Xiao joined the Hyman Lab with a strong background in protein quality control and a deep interest in the physical principles behind protein phase behavior. His research focuses on understanding how cellular stress and molecular interactions lead to pathological phase transitions, using a powerful combination of cell biology, imaging, and biochemical reconstitution. This publication reflects the culmination of his rigorous and creative work over the past years. His contributions significantly advance our understanding of how stress granules can act as crucibles for disease-related protein aggregation.
🔬 About David Kuster
David earned his M.Sc. in Biochemistry at the Universität Heidelberg. He has a long-standing interest in RNA biology and biomolecular condensates. After completing an internship at MPI-CBG, he joined the Hyman lab for his PhD, where he focuses on the SARS-CoV-2 nucleocapsid protein and other RNA-binding proteins. His work is funded by the Volkswagen Foundation. Outside the lab, David is a passionate birdwatcher.
🔬 About Jik Nijssen
Jik did his master’s in neuroscience in Maastricht (Netherlands), followed by a PhD in the field of neurodegeneration, specifically focusing on the genetic origins of amyotrophic lateral sclerosis (ALS). He joined the Hyman lab in 2021 with an expertise in modeling neurodegeneration in a dish, using cell lines, human stem cells, and neurons. With an interest in TDP-43 protein aggregation, Jik teamed up with Xiao Yan (Andy) and David and performed live- and fixed cell microscopy, as well as high-throughput data quantification for this publication. Coupled with the expertise of the other authors in biochemistry and in vitro protein work, this created a complementary research team that could study TDP-43 in a range of systems and scales. Together, this resulted in the recent publication covering TDP-43 aggregation from multiple angles and driving our understanding of this ALS-related process forward.
Congratulations to Andy, David, and Jik on this important milestone in their scientific career!