Our Research
The dynamic regulation of the proteome is critical for cell survival and function. We are identifying the proteins and signaling pathways that coordinate mRNA translation to prevent catastrophic proteostasis collapse.
We are applying molecular genetics, fluorescence microscopy, genome editing, and ribosome profiling approaches to study the intersection of translation and protein quality control.
Defects in protein degradation, RNA-protein granules, and protein synthesis are associated with aging and degenerative diseases. A mechanistic understanding of proteostasis will aid in the development of new therapeutic approaches to improve health across the lifespan. This research is supported by the NIGMS/NIH, a pilot grant from the Paul F. Glenn Center for the Biology of Aging Research at the University of Michigan, and a collaborative Michigan-Israel partnership award.
Molecular Mechanisms of VCP Disease
Mutations in the VCP gene are associated with amyotrophic lateral sclerosis, inclusion body myopathy, Paget disease of the bone, frontotemporal dementia, and vacuolar tauopathy reminiscent of Alzheimer’s disease.
We are determining how these mutations impact VCP function and the RNA biology of mammalian cells.
This research is supported by the Chan Zuckerberg Initiative Neurodegeneration Challenge Network, the Robert Packard Center for ALS Research, and the LiveLikeLou Foundation. We are also part of the Cure VCP Disease, Inc. scientific focus group.
Genetic Diseases of the Integrated Stress Response
The integrated stress response is the rapid and reversible remodeling of gene expression that allows eukaryotes to adapt to stress. A growing number of genetic disorders are associated with mutant alleles of genes that encode integrated stress response factors.
We are determining whether and how these mutations in integrated stress response genes impair cellular resilience and adaptation to stress using molecular genetics, genome editing, and live cell fluorescence microscopy approaches.
This research is supported by the Dystonia Medical Research Foundation, the Brain & Behavior Research Foundation, and the University of Michigan Neuroscience Scholars Program.