iNeuron
DNA/RNA/protein

Species-Specific Proteostasis

Proteostasis broadly describes all processes which work to maintain protein balance within the cell, including synthesis, folding, and degradation. Our lab investigates how proteostasis differs between species, an area which has important implications for therapeutic development in model systems.

Tissue-Specific Proteostasis

Our group explores tissue-specific proteostasis with a focus on NPC1 proteostasis in liver and brain, the two organs most affected in Niemann-Pick type C disease. Our investigations seek to identify whether tissue-specific therapeutics may be required to combat Niemann-Pick type C disease symptom progression.

Mutation-Specific Proteostasis

There are over 250 known mutations which cause Niemann-Pick type C disease, and different mutations can undergo differential proteostasis. For example, our group reported that I1061T and P1007A fibroblasts respond differently to inhibitors of ERAD and ER-phagy.  Further work to study mutation-specific proteostasis can open possibilities for individualized patient care.

mRNA Therapeutics

We are actively investigating the use of Niemann-Pick C mRNA therapeutics to restore the normal NPC1 mRNA. This should result in the production of wild-type NPC1 protein and the correction of Niemann-Pick C phenotypes including cholesterol storage and aberrant autophagy activation.