Ongoing projects: 

Here are some projects we are currently focused on:

1. Develop a mouse model and a gene therapy for MTATP6 Leigh syndrome

We are developing the first disease-relevant mouse model and an AAV-based gene therapy for mitochondrial DNA-encoded ATPase 6 (MTATP6)-related mitochondrial diseases. Mutations in MTATP6 are the most common cause of impaired mitochondrial ATP synthesis, leading to neurological mitochondrial diseases. There are currently no approved treatments for any of its disease forms. Unlike the vast majority of genes that are being targeted for gene therapy, the MTATP6 gene is encoded in the mitochondrial genome, which poses greater challenges.

2. Develop a gene therapy for NF2-related schwannomatosis

Neurofibromatosis type 2-related schwannomatosis (NF2-SWN) is a rare, inherited tumor predisposition syndrome characterized by the development of multiple benign tumors of the nervous system, particularly bilateral vestibular schwannomas. It is caused by loss-of-function mutations in the NF2 gene, which encodes the tumor suppressor protein MERLIN. We are developing a gene therapy for this devastating disease.

3. Develop genetic tools targeting specific cell states with mitochondrial dysfunctions

Mitochondria requires precise protein expression, but a major challenge for developing a precise gene therapy approach is the lack of understanding of the endogenous regulatory mechanisms. Therefore, we aim to answer the questions of how protein expressions are regulated and whether these regulations are tissue or cell-specific. We will then leverage on this information to enhance the design of our gene therapy approach for better efficacy and safety.