Novel AAV systems
In parallel to our studies on retinal proteostasis, we also leverage our background in protein biochemistry and biophysics to develop novel AAV systems, in collaboration with the Byrne lab at the University of Pittsburgh. With a packaging capacity of 4.7Kb, AAVs are currently not suitable for the delivery of large genes that are needed to treat diseases such as Usher syndrome type 1F or Stargardt disease, or to deliver large genome editing tools such as prime editors. To overcome this limitation, we are engineering novel AAV capsid systems for the efficient delivery of large therapeutic payloads.
Protein homeostasis in photoreceptor disease
Proteopathies, where mutations in proteins prevent their proper folding, are one of the main causes behind many retinal degenerative diseases including autosomal dominant Retinitis Pigmentosa. In proteopathies, the increased amount of misfolded protein poses a tremendous burden on retinal cells, which must now allocate a large part of their proteostatic machinery to recognizing, attempting to fold, and degrading misfolded proteins. This severely limits the proteostatic capacity available to the rest of proteins for normal cell function and greatly reduces the cell’s ability to overcome additional stress and aging, resulting in premature cell death and leading to impaired vision and blindness.
Our research is centered on identifying and characterizing proteostatic mechanisms that can be therapeutically delivered to diseased photoreceptors to increase their proteostatic capacity, preserving cellular health and delaying disease progression.