Research

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, tissues and mutations. Understanding species specific differences has important implications for therapeutic development in model systems. Tissue specific proteostasis is imperative to study as Niemann Pick Type C1 affects the liver and the brain primarily while in GSD III the liver and skeletal muscle are the primary tissues affected. The wide variety of variants associated with both Niemann Pick Type C1 and GSD III can undergo differential proteiostasis and can open possibilities for individualized patient care.

iPSC Modeling

The development of effective therapeutics for human patients will require the generation of humanized models. To address this need, our lab utilizes human induced pluripotent stem cells (iPSCs) to model disease phenotypes in a cell specific way. As iPSCs have the potential to differentiate into any autonomous cell type, the lab makes hepatocytes, neurons, astrocytes, macrophages and myotubes to model Neimann Pick Type C1 disease and GSD III. Small molecules and transcription factor-based expression drives differentiation. Functional characterization in vitro is imperative for early disease characterization and therapeutic screening. iPSC’s can be isogenic or patient derived providing a disease relevant cell model in which targeted research can occur.

mRNA Therapeutics

We are actively investigating the use of mRNA therapeutics to restore the normal NPC1 or GDE mRNA. This should result in the production of wild-type NPC1 or GDE protein and lead to the correction of disease phenotypes. Utilizing lipid nanoparticles for delivery we are investigating novel formulations for tissue targeted effects.