A5020093028- Melanoma and MAPK Pathways
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
- Transgenic Plants and Applications
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Protein Degradation and Inhibitors
- Cancer Cells and Metastasis
- Glycosylation and Glycoproteins Research
- Cellular Mechanics and Interactions
- RNA Research and Splicing
- ATP Synthase and ATPases Research
University of California, Santa Barbara
2023
University of Colorado Boulder
2020-2021
Abstract Despite the increasing number of effective anti-cancer therapies, successful treatment is limited by development drug resistance. While contribution genetic factors to resistance undeniable, little known about how drug-sensitive cells first evade action proliferate in drug. Here we track responses thousands single melanoma BRAF inhibitors and show that a subset escapes via non-genetic mechanisms within three days treatment. Cells escape rely on ATF4 stress signalling cycle...
The heterohexameric ATPases associated with diverse cellular activities (AAA)-ATPase Pex1/Pex6 is essential for the formation and maintenance of peroxisomes. Pex1/Pex6, similar to other AAA-ATPases, uses energy from ATP hydrolysis mechanically thread substrate proteins through its central pore, thereby unfolding them. In related AAA-ATPase motors, substrates are recruited binding motor's N-terminal domains or N terminally bound cofactors. Here, we use structural biochemical techniques...
Abstract Despite increasing numbers of effective anti-cancer therapies, successful treatment is limited by the development drug resistance. While contribution genetic factors to resistance undeniable, little known about how drug-sensitive cells first evade action proliferate in drug. Here we track response thousands single melanoma BRAF inhibitors and show that a subset escapes within 3 days treatment. Cell-cycle re-entry occurs via non-genetic mechanism involving activation mTORC1 ATF4,...
While loop motifs frequently play a major role in protein function, our understanding of how to rationally engineer proteins with novel domains remains limited. In the absence rational approaches, incorporation often destabilizes proteins, thereby requiring massive screening and selection identify sites that can accommodate insertion. We developed computational strategy for rapidly scanning entire structure scaffold determine impact insertion at all possible amino acid positions. This...
The heterohexameric AAA-ATPase Pex1/Pex6 is essential for the formation and maintenance of peroxisomes. Pex1/Pex6, similar to other AAA-ATPases, uses energy from ATP hydrolysis mechanically thread substrate proteins through its central pore, thereby unfolding them. In related motors, substrates are recruited binding motor's N-terminal domains or N-terminally bound co-factors. Here we use structural biochemical techniques characterize function N1 domain in Pex6 budding yeast,