Torres Gutierrez, Mauricio Andres
Primary Appointment
Research Assistant Professor, Molecular Physiology and Biological Physics
Contact Information
Email: cwr5zs@virginia.edu
Research Disciplines
Biochemistry, Biology, Metabolism, Molecular and Cellular Physiology, Neuroscience
Research Interests
I study how neurons maintain protein homeostasis and how its disruption drives neurodegeneration. Focusing on the SEL1L–HRD1 ERAD complex in neuron-specific knockout mice, I show ER proteostasis is critical for circuit stability and survival, integrating genetics and multi-omics to identify mechanisms and targets.
Research Description
My research investigates how neurons maintain protein homeostasis and how disruptions in this process contribute to neurodegeneration. Neurons are particularly vulnerable to defects in protein quality control because they are long-lived and highly specialized. I focus on the SEL1L–HRD1 complex, a core component of the endoplasmic reticulum–associated degradation (ERAD) pathway, which eliminates misfolded proteins from the ER. Using neuron-specific conditional knockout mouse models, including Synapsin-Cre–driven deletion of Sel1L, we demonstrated that neuronal ERAD is essential for motor coordination, behavioral regulation, and survival. Loss of SEL1L in neurons leads to partial activation of unfolded protein response pathways and cell-type–specific transcriptional remodeling in the cortex and hippocampus. Our work reveals that ER protein quality control is a critical determinant of neural circuit stability rather than merely a passive housekeeping mechanism. By integrating mouse genetics, single-nucleus RNA sequencing, proteomics, imaging, and behavioral analyses, my research aims to define the molecular mechanisms linking ER proteostasis to neuronal function and to identify therapeutic strategies for neurodegenerative diseases.