A5042273166- Protein Degradation and Inhibitors
- Endoplasmic Reticulum Stress and Disease
- Parkinson's Disease Mechanisms and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Fungal and yeast genetics research
- Gene Regulatory Network Analysis
- Cell Image Analysis Techniques
- Insect Resistance and Genetics
- Viral Infectious Diseases and Gene Expression in Insects
- Traumatic Brain Injury Research
- Traumatic Brain Injury and Neurovascular Disturbances
- Plant-derived Lignans Synthesis and Bioactivity
- Heat shock proteins research
- Lignin and Wood Chemistry
- Immune Response and Inflammation
- Signaling Pathways in Disease
- Monoclonal and Polyclonal Antibodies Research
- Cardiac Arrest and Resuscitation
- Single-cell and spatial transcriptomics
- Click Chemistry and Applications
- Antimicrobial Peptides and Activities
- Bacillus and Francisella bacterial research
- Yersinia bacterium, plague, ectoparasites research
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
Dana-Farber Cancer Institute
2023
Harvard University
2023
University of California, San Francisco
2018-2022
Howard Hughes Medical Institute
2022
Great Lakes Bioenergy Research Center
2018
University of Wisconsin–Madison
2018
Williams College
2017
Significance Traumatic brain injury (TBI) occurs when a strong jolt to the head causes damage cells, resulting in immediate and long-term consequences including physical, behavioral, cognitive problems. Despite importance of TBI as major health issue, our understanding underlying cellular molecular mechanisms is limited. To unravel these mechanisms, we have developed model fruit fly, Drosophila melanogaster , where can apply many powerful experimental tools. The main features human also...
The search for cell-permeable drugs has conventionally focused on low-molecular weight (MW), nonpolar, rigid chemical structures. However, emerging therapeutic strategies break traditional drug design rules by employing flexibly linked entities composed of more than one ligand. Using complementary genome-scale chemical-genetic approaches we identified an endogenous uptake pathway involving interferon-induced transmembrane proteins (IFITMs) that modulates the cell permeability a prototypical...
ABSTRACT Although the primary protein sequence of ubiquitin (Ub) is extremely stable over evolutionary time, it highly tolerant to mutation during selection experiments performed in laboratory. We have proposed that this discrepancy results from difference between fitness under laboratory culture conditions and selective pressures changing environments timescales. Building on our previous work (Mavor et al., 2016), we used deep mutational scanning determine how twelve new chemicals...
To address the growing need for new antimicrobial agents, we explored whether inhibition of bacterial signaling machinery could inhibit growth. Because bacteria rely on two-component systems to respond environmental changes, and because these are both highly conserved mediated by histidine kinases, inhibiting kinases may provide broad spectrum activity. The kinase ATP binding domain is with ATPase eukaryotic Hsp90 molecular chaperones. find a chemical scaffold compounds that target leveraged...
Protein conformations are shaped by cellular environments, but how environmental changes alter the conformational landscapes of specific proteins in vivo remains largely uncharacterized, part due to challenge probing protein structures living cells. Here, we use deep mutational scanning investigate a toxic conformation α-synuclein, dynamic linked Parkinson's disease, responds perturbations proteostasis. In context course for graduate students UCSF Integrative Program Quantitative Biology,...
Mammalian target of rapamycin (mTOR) is a highly conserved eukaryotic protein kinase that coordinates cell growth and metabolism, plays critical role in cancer, immunity, aging. It remains unclear how mTOR signaling individual tissues contributes to whole-organism processes because inhibitors, like the natural product rapamycin, are administered systemically multiple simultaneously. We developed chemical-genetic system, termed selecTOR, restricts activity analog specific populations through...
Abstract mTOR is a highly conserved eukaryotic protein kinase that coordinates cell growth and metabolism plays critical role in cancer, immunity, aging. It remains unclear how signaling individual tissues contributes to whole-organism processes because inhibitors, like the natural product Rapamycin, are administered systemically target multiple simultaneously. We developed chemical-genetic system, termed selecTOR, restricts activity of Rapamycin analog specific populations through targeted...
Abstract Activation of phosphatidylinositol 3-kinase (PI3K)/PTEN pathway and oncogenic signaling via the mechanistic target rapamycin (mTOR) occur in a majority high-grade glial brain tumors. Allosteric mTOR inhibitors, such as other rapalogs, incompletely block mTORC1 by reducing phosphorylation some substrates, including S6K1, but not 4EBP1. In contrast, ATP-competitive sapanisertib, fully inhibit mTORC1. However these inhibitors are also active against mTORC2 lipid kinases, likely...
ABSTRACT Protein conformations are shaped by cellular environments, but how environmental changes alter the conformational landscapes of specific proteins in vivo remains largely uncharacterized, part due to challenge probing protein structures living cells. Here, we use deep mutational scanning investigate a toxic conformation α-synuclein, dynamic linked Parkinson’s disease, responds perturbations proteostasis. In context course for graduate students UCSF Integrative Program Quantitative...
Abstract Summary Cellpanelr is an open-source R package and web application for analyzing user-generated cell panel screens using DepMap data sets. can be used to identify mutation expression biomarkers of line response, increasing the value accessibility experiments such as relative sensitivities cancer drugs. Availability implementation Hosted available from shinyapps.io ( https://dwassarman.shinyapps.io/cellpanelr ). Source code installation instructions are GitHub...