Education & Training
- 2021 - Present: Research Assistant Professor, Department of Ophthalmology, University of Pittsburgh School of Medicine
- 2019 - 2021: Postdoctoral Fellow, Laboratory of Jeffrey Brodsky, Department of Biological Sciences, University of Pittsburgh
- 2012 - 2019: PhD in Biophysics, Laboratory of David Agard, University of California San Francisco
- 2000 - 2005: BSc in Artificial Intelligence and Computer Science, The University of Edinburgh, UK
For a full list of publications, click here.
The proper folding of proteins is of vital importance for cellular function and viability. Cells have therefore evolved varied mechanisms to ensure and monitor proper protein folding and degrade misfolded proteins. If the burden of misfolded proteins is too large, pro-apoptotic pathways are activated, resulting in cell death. In photoreceptors this leads to irreversible cell loss and blindness. Proteopathies are indeed one of the main causes behind many retinal degenerative diseases, such as retinitis pigmentosa, where mutations that destabilize the native state of proteins such as rhodopsin lead to reduced vision and eventual blindness. Our research is centered on identifying and characterizing, with unprecedented breadth and detail, mechanisms by which photoreceptors maintain adequate proteostasis during disease, with the ultimate goal of leveraging these mechanisms to enable the development of new therapies. While previous work has evaluated the role of a handful of general chaperones such as Hsp40 or Hsp90, the proteostasis network is composed of thousands of proteins that perform highly different functions and exhibit finely tuned substrate specificity. We employ novel methods such as high-content imaging-based CRISPRi screens and proximity-labeling MS/MS assays to simultaneously examine the role of thousands of components of the proteostasis network in the folding, trafficking and degradation of disease mutants of critical photoreceptor proteins such as rhodopsin, PRPF31 and peripherin-2. We follow up on these findings with biochemical, biophysical and structural studies to fully characterize these mechanisms.