Dr. Eric Vitriol

Current Projects

The role of PFN1 in organelle homeostasis

Profilin 1 (PFN1) is a key player in cellular structure and function, serving as the predominant actin monomer-binding protein in mammalian cells. Recent studies into the pathogenic mechanisms caused by PFN1 mutations have greatly expanded our understanding of its crucial role in cellular physiology. For example, we have discovered that PFN1 is essential for maintaining mitochondrial integrity, with the loss of PFN1 expression leading to the accumulation of depolarized, dysmorphic mitochondria. Surprisingly, this disruption in mitochondrial homeostasis is believed to result from a specific and novel role of PFN1 within the mitochondrial matrix. Additionally, we have identified critical functions for PFN1 in regulating the clearance of damaged organelles and the endoplasmic reticulum. However, many questions about PFN1’s role in these processes remain. We are now employing novel methods to spatiotemporally manipulate profilin expression and function, allowing us to distinguish between cause and effect and to assess both the direct actions of PFN1 and potential indirect effects arising from cytoplasmic actin assembly. These techniques are combined with super-resolution microscopy and spatial proteomics to elucidate the specific, mechanistic roles of profilin in organelle homeostasis.

Dysregulation of actin in neurodegenerative disease

Another of my lab’s interests is understanding the connection between the actin cytoskeleton and neurodegenerative diseases like amyotrophic lateral sclerosis (ALS). Actin was first implicated in ALS when it was discovered that mutations in PFN1, a gene that encodes an actin-binding protein, cause a hereditary form of the disease. We currently have projects in the lab determining how ALS-linked mutants disrupt actin in ways that could contribute to neurodegeneration. We have also begun to investigate how dysregulation of actin in neuronal processes contributes to Alzheimer’s and Parkinson’s disease. We use neurons differentiated from human stem cells as a translational model for neurodegeneration in the lab. We then apply spatial proteomics, expansion microscopy, and super-resolution imaging to identify the early molecular events that cause toxicity and cell death.