Ruth Chia
Staff Scientist NIH
Seminars
Wednesday 3rd June 2026
Panel Discussion: What Happens Upstream of TDP-43 Misfolding? Shifting Focus from Restoring Function to Understanding Root Cause of Aggregate Pathology
9:30 am
- What are the earliest cellular events that trigger TDP-43 mislocalization and aggregation, and how do these upstream mechanisms vary across ALS subtypes?
- How do general protein homeostasis pathways, including nuclear import/export and stress response mechanisms, influence TDP-43 pathology?
- Which cryptic exons, epigenetic changes, or C9orf72-related mechanisms are likely contributors to disease initiation, and how should these inform target prioritization?
- How can we improve ALS model systems to better reflect the physiological context of TDP-43 misfolding and aggregate formation?
- Moving beyond restoring TDP-43 function, what strategies can drug developers adopt to intervene at the root cause of aggregate pathology?
Wednesday 3rd June 2026
A Plasma Proteomic Biomarker Panel for Early Detection & Disease Prediction in ALS
11:30 am
- Utilizing high throughput plasma proteomics to define a 33 protein biomarker panel that differentiates ALS from controls and other neurological diseases with high classification accuracy
- Applying machine learning to integrate plasma protein levels with clinical features, achieving robust diagnostic performance (AUC ~98%) and a composite ALS risk score
- Demonstrating that shifts in the proteomic risk score emerge years (up to ~10 yrs) before clinical symptom onset, highlighting a prodromal phase amenable to early detection and intervention
- Discussing how multi protein signatures and pathway insights (skeletal muscle, neuronal and energy metabolism processes) can inform prognostic stratification and future therapeutic targeting, including broader validation and global applicability
