Our work centers on the crosstalk between proteins and genes. We are studying how mechanisms that ensure protein quality regulate transcription, translation, and metabolism. The goal of this research is to understand, and eventually control, molecular mechanisms that are critical for aging and cancer.
Site-specific Protein Removal in Transcriptional and Epigenetic Regulation
The ubiquitin-proteasome system is the principal cellular mechanism for selective protein removal. Transcription factors and chromatin modifiers are short-lived proteins and associated with defined DNA regions. The activity as well as the elimination of these proteins occur in a site-specific context. We study which elements of the ubiquitin-proteasome system are involved in spatially restricted degradation…
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Proteome Integrity in Aging Hematopoietic Stem Cells
Loss of protein quality is a driving force of aging. Misfolded proteins accumulate over time and represent a vulnerability for long-lived cells, such as blood stem cells. How these cells avert the effects of aging and maintain a high regenerative potential is poorly understood. We investigated the expression and function of the most highly expressed…
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The Role of Mitochondrial Proteases in Cancer
Mitochondria are appreciated for their role in metabolism. It is less well understood how they contribute to protein homeostasis. Mitochondria contain several proteases that can exit into the cytosol. Also, extramitochondrial proteins can be transported into these organelles for degradation. The main cytosolic machinery that degrades proteins is the proteasome. Inhibitors of the proteasome are…
By identifying critical chaperones and proteases, we aim to intervene with pathways that drive aging and growth in stem cells and cancers.