A5031380030- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Computational Drug Discovery Methods
- CRISPR and Genetic Engineering
- Click Chemistry and Applications
- CAR-T cell therapy research
- Multiple Myeloma Research and Treatments
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Innovative Microfluidic and Catalytic Techniques Innovation
- Neonatal Respiratory Health Research
- Ferroptosis and cancer prognosis
- COVID-19 Clinical Research Studies
- Pancreatic function and diabetes
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- Peptidase Inhibition and Analysis
- Tracheal and airway disorders
- Chemical Synthesis and Analysis
- Tannin, Tannase and Anticancer Activities
- Microbial Natural Products and Biosynthesis
- HIV Research and Treatment
- Respiratory Support and Mechanisms
- vaccines and immunoinformatics approaches
- Calcium signaling and nucleotide metabolism
Gladstone Institutes
2023-2024
University of California, Berkeley
2016-2023
Innovative Genomics Institute
2021
Novartis (Switzerland)
2018-2021
Targeted protein degradation has arisen as a powerful strategy for drug discovery allowing the targeting of undruggable proteins proteasomal degradation. This approach most often employs heterobifunctional degraders consisting protein-targeting ligand linked to an E3 ligase recruiter ubiquitinate and mark interest One challenge with this approach, however, is that only few recruiters currently exist targeted applications, despite hundreds known ligases in human genome. Here, we utilized...
Abstract Prime editing enables the precise modification of genomes through reverse transcription template sequences appended to 3′ ends CRISPR–Cas guide RNAs 1 . To identify cellular determinants prime editing, we developed scalable reporters and performed genome-scale CRISPR-interference screens. From these screens, a single factor emerged as strongest mediator editing: small RNA-binding exonuclease protection La. Further investigation revealed that La promotes across approaches (PE2, PE3,...
Most of the proteome is considered undruggable, oftentimes hindering translational efforts for drug discovery. Identifying previously unknown druggable hotspots in proteins would enable strategies pharmacologically interrogating these sites with small molecules. Activity-based protein profiling (ABPP) has arisen as a powerful chemoproteomic strategy that uses reactivity-based chemical probes to map reactive, functional, and ligandable complex proteomes, which enabled inhibitor discovery...
One-carbon metabolism is an essential branch of cellular that intersects with epigenetic regulation. In this work, we show how formaldehyde (FA), a one-carbon unit derived from both endogenous sources and environmental exposure, regulates by inhibiting the biosynthesis
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), has emerged as a major global health threat. The COVID-19 pandemic resulted in over 168 million cases and 3.4 deaths to date, while number continues rise. With limited therapeutic options, identification safe effective therapeutics is urgently needed. repurposing known clinical compounds holds potential for rapid drugs against SARS-CoV-2. Here, we utilized library FDA-approved...
While vaccines and antivirals are now being deployed for the current SARS-CoV-2 pandemic, we require additional antiviral therapeutics to not only effectively combat its variants, but also future coronaviruses. All coronaviruses have relatively similar genomes that provide a potential exploitable opening develop therapies will be effective against all Among various genes proteins encoded by coronaviruses, one particularly "druggable" or easy-to-drug target is coronavirus Main Protease...
Abstract Targeted protein degradation is a powerful therapeutic modality that uses heterobifunctional small-molecules to induce proximity between E3 ubiquitin ligases and target proteins ubiquitinate degrade specific of interest. However, many are ubiquitinated degraded drive disease pathology; in these cases targeted stabilization (TPS), rather than degradation, the actively using small-molecule would be therapeutically beneficial. Here, we present Deubiquitinase-Targeting Chimera (DUBTAC)...
Abstract Nimbolide, a terpenoid natural product derived from the Neem tree, impairs cancer pathogenicity across many types of human cancers; however, direct targets and mechanisms by which nimbolide exerts its effects are poorly understood. Here, we used activity-based protein profiling (ABPP) chemoproteomic platforms to discover that reacts with novel functional cysteine crucial for substrate recognition in E3 ubiquitin ligase RNF114. Nimbolide breast cell proliferation in-part disrupting...
Abstract While vaccines and antivirals are now being deployed for the current SARS-CoV-2 pandemic, we require additional antiviral therapeutics to not only effectively combat its variants, but also future coronaviruses. All coronaviruses have relatively similar genomes that provide a potential exploitable opening develop therapies will be effective against all Among various genes proteins encoded by coronaviruses, one particularly “druggable” or easy-to-drug target is coronavirus Main...
Abstract Targeted protein degradation has arisen as a powerful strategy for drug discovery allowing the targeting of undruggable proteins proteasomal degradation. This approach most often employs heterobifunctional degraders consisting protein-targeting ligand linked to an E3 ligase recruiter ubiquitinate and mark interest One challenge with this approach, however, is that only few recruiters currently exist targeted applications, despite hundreds known ligases in human genome. Here, we...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of disease 2019 (COVID-19), has emerged as a major global health threat. The COVID-19 pandemic resulted in over 80 million cases and 1.7 deaths to date while number continues rise. With limited therapeutic options, identification safe effective therapeutics is urgently needed. repurposing known clinical compounds holds potential for rapid drugs against SARS-CoV-2. Here we utilized library FDA-approved...
The initiation and execution of cell death is regulated by various lipids. How the levels environmental (exogenous) lipids impact sensitivity not well understood. Using a high-throughput lipid modulation screen we find that physiological extracellular free fatty acids have diverse effects on non-apoptotic apoptotic induced lethal small molecules natural products. In particular, monounsaturated (MUFAs) are found to suppress non-apoptotic, iron-dependent process ferroptosis. This protective...