A5068828788- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- interferon and immune responses
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- MicroRNA in disease regulation
- Cannabis and Cannabinoid Research
- Cancer-related gene regulation
- Sirtuins and Resveratrol in Medicine
- Adenosine and Purinergic Signaling
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- Calcium signaling and nucleotide metabolism
- PARP inhibition in cancer therapy
- Cytomegalovirus and herpesvirus research
- Cancer, Lipids, and Metabolism
- Ubiquitin and proteasome pathways
- Cancer, Hypoxia, and Metabolism
- Genomics, phytochemicals, and oxidative stress
- Conferences and Exhibitions Management
- ATP Synthase and ATPases Research
- RNA regulation and disease
- Peptidase Inhibition and Analysis
Salk Institute for Biological Studies
2021-2024
University of Colorado Denver
2015-2021
University of Colorado Anschutz Medical Campus
2015-2021
Abstract Autophagic receptor p62 is a critical mediator of cell detoxification, stress response, and metabolic programs commonly deregulated in human diseases. The diverse functions arise from its ability to interact with large set ligands, such as arginylated (Nt-R) substrates. Here, we describe the structural mechanism for selective recognition Nt-R by ZZ domain (p62 ). We show that binding substrates stimulates aggregation macroautophagy required autophagic targeting p62. essential mTORC1...
Abstract TP53 is mutated in 50% of all cancers, and its function often compromised cancers where it not mutated. Here we demonstrate that the pro-tumorigenic/metastatic Six1 homeoprotein decreases p53 levels through a mechanism does involve negative regulator p53, MDM2. Instead, regulates via dual involving upregulation microRNA-27a downregulation ribosomal protein L26 (RPL26). Mutation analysis confirms RPL26 inhibits miR-27a binding prevents microRNA-mediated p53. The clinical relevance...
Invasive lobular carcinoma of the breast (ILC) is strongly estrogen-driven and represents a unique context for estrogen receptor (ER) signaling. In ILC, ER controls expression Wnt ligand WNT4, which critical endocrine response anti-estrogen resistance. However, signaling mediated by WNT4 cell type- tissue-specific, has not been explored in ILC. We utilized reverse phase protein array (RPPA) to characterize WNT4-driven ILC cells identified that mediates downstream mTOR via phosphorylation S6...
Mitochondria are critical organelles that maintain cellular metabolism and overall function. The catabolic pathway of autophagy plays a central role in recycling damaged mitochondria. Although the is indispensable for some cancer cell survival, our latest study shows rare autophagy-dependent cells can adapt to loss this core pathway. In process, autophagy-deficient acquire unique dependencies on alternate forms mitochondrial homeostasis. These clones circumvent lack canonical by increasing...
Macroautophagy/autophagy degrades proteins and organelles to generate macromolecular building blocks. As such, some cancer cells are particularly dependent on autophagy. In a previous paper, we found that even highly autophagy-dependent can adapt circumvent autophagy inhibition. However, it remains unclear if could survive the complete elimination of autophagosome formation. We extended our findings show knockout (KO) both upstream regulator RB1CC1/FIP200 downstream mediator LC3 conjugation,...
TRAIL is a potent death-inducing ligand that mediates apoptosis through the extrinsic pathway and serves as an important endogenous tumor suppressor mechanism. Because cells are often killed by normal not, drugs activate have been thought to potential clinical value. However, date, most TRAIL-related trials largely failed due having intrinsic or acquired resistance TRAIL-induced apoptosis. Previous studies identify mechanisms focused on targeted analysis of canonical other known regulators...
Maternally inherited mitochondrial DNA (mtDNA) encodes essential subunits of the oxidative phosphorylation system, but is also a major damage-associated molecular pattern (DAMP) that engages innate immune sensors when released into cytoplasm, outside cells or circulation 1 . This function mtDNA contributes to antiviral resistance, unfortunately causes pathogenic inflammation in many disease contexts 2 Cells experiencing stress due depletion mtDNA-packaging protein, Transcription Factor A,...
Autophagy is a central recycling process, and it plays complex role in cancer. We discovered that when autophagy blocked, cancer cells compensate by increasing mitochondrial-derived vesicles. However, there are many unanswered questions remaining, particularly the context of dual roles