Drug Discovery and Testing
I connect mechanistic insights to therapeutic development by testing small molecules that target neurodegeneration and infection. My work spans novel Parkin agonists, TAC compounds, lysosomal rescue strategies, and host-directed antivirals
Parkin Agonist Development
I collaborated with chemical biologists to identify small-molecule activators of Parkin, a ubiquitin ligase central to mitochondrial quality control. In dopaminergic neurons, Parkin agonists enhanced mitophagy, improved survival, and protected against α-synuclein–induced degeneration. These results positioned Parkin activation as a promising therapeutic approach for modifying Parkinson’s disease progression (Manuscript in preparation).
TAC Evaluation
I evaluated a Telomerase Activating Compound (TAC) designed to enhance neuronal resilience by targeting pathways linked to mitochondrial and lysosomal biology. In iPSC-derived neurons, TAC treatment reduced α-synuclein pathology and senescence markers, illustrating how rationally engineered molecules can engage convergent protective mechanisms in neurodegeneration (Manuscript in preparation).
PAH and Lysosomal Rescue
Although previously discovered, I used Perillaldehyde (PAH) to restore lysosomal function in dopaminergic neurons challenged with α-synuclein fibrils and cytokines. Enhancing lysosomal activity alleviated lysosomal stress, reduced inclusion burden, and preserved neuronal health, demonstrating the therapeutic potential of metabolic interventions. These results exhibit a new functionality and potential therapeutic ability of PAH for Parkinson's disease pathology.
Western blot analysis shows that PFF+IFN-γ treatment reduces lysosomal proteins (LAMP1, LAMP2) and regulators (NRF2, TFEB) while increasing α-syn pathology. The addition of PAH restored lysosomal proteins.
PIKfyve as an Antiviral Target
I co-developed a selective inhibitor of the lipid kinase PIKfyve and demonstrated its essential role in SARS-CoV-2 infection. Inhibition of PIKfyve blocked viral trafficking to lysosomes and prevented replication, providing both a tractable therapeutic target and a mechanistic tool for probing endolysosomal biology.
Internalization of spike protein (green) by Calu-3 cells, which express the ACE2 receptor. This internalization was reduced with CSNK2 inhibitors.
Internalization of spike protein (green) by Caco-2 cells, which express ACE2 receptor. This internalization was reduced with PIKfyve inhibitors.
CSNK2 as an Antiviral Target
Through mechanistic studies, I identified casein kinase 2 (CSNK2) as another critical host factor for SARS-like coronaviruses. Pharmacological inhibition of CSNK2 suppressed replication across multiple viral strains, highlighting it as a promising broad-spectrum antiviral target and underscoring the role of host kinases in viral exploitation of cellular trafficking.