A5087388847- Protein Kinase Regulation and GTPase Signaling
- Receptor Mechanisms and Signaling
- Protein Degradation and Inhibitors
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Cancer-related gene regulation
- Metabolomics and Mass Spectrometry Studies
- Enzyme Structure and Function
- Health, Environment, Cognitive Aging
- Gut microbiota and health
- Microbial Metabolic Engineering and Bioproduction
- Pancreatic function and diabetes
- Neuroscience and Neuropharmacology Research
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
- Bioinformatics and Genomic Networks
- Viral Infectious Diseases and Gene Expression in Insects
- Science, Research, and Medicine
- Biochemical and Molecular Research
AstraZeneca (Singapore)
2025
Stevenage Bioscience Catalyst
2024
AstraZeneca (United Kingdom)
2020-2024
Institute for Stem Cell Biology and Regenerative Medicine
2020
The University of Texas Southwestern Medical Center
2010-2016
Center for Systems Biology
2016
Southwestern Medical Center
2015
Unlocking novel E3 ligases for use in heterobifunctional PROTAC degraders is of high importance to the pharmaceutical industry. Over-reliance on current suite ligands used recruit could limit potential their application. To address this, potent DCAF15 were optimized using cryo-EM supported, structure-based design improve micromolar starting points. A binder, compound 24, was identified and subsequently conjugated into PROTACs against multiple targets. Following attempts degrading a number...
Mammalian phospholipase C-β (PLC-β) isoforms are stimulated by heterotrimeric G protein subunits and members of the Rho GTPase family small proteins. Although recent structural studies showed how Gαq Rac1 bind PLC-β, there is a lack consensus regarding Gβγ binding site in PLC-β. Using FRET between cerulean fluorescent protein-labeled Alexa Fluor 594-labeled PLC-β pleckstrin homology (PH) domain, we demonstrate that PH domain minimal region PLC-β3. We show isolated can compete with...
Methionine, through
Abstract In recent years, helicases have moved to the forefront of research as novel drug targets for a variety human diseases, including cancer. As critical components cell cycle and DNA repair, these enzymes offer an attractive point therapeutic intervention. Recent bioinformatic endeavours such Cancer DepMap further highlighted essentiality proteins in progression numerous cancers. Inhibitors Werner helicase (WRN) entered Phase I evaluation 2023, after studies its role tumours with...
Abstract Maintenance of telomeres in the absence telomerase is known as Alternative Lengthening Telomeres (ALT), which prevalent 10-15% all cancers. Tessellate BIO targets ALT mechanisms to drive cell death by synthetic lethality. To identify patients who will benefit from our therapy, we are developing companion diagnostics (CDx). In this study, established hallmarks investigated CDx target tissue-derived samples. fresh and FFPE tumor tissue, presence abundance different were measured,...
Abstract A proteolysis targeting chimera (PROTAC) is a new technology that marks proteins for degradation in highly specific manner. During screening, PROTAC compounds are tested concentration-response (CR) assays to determine their potency, and parameters such as the half-maximal concentration (DC 50 ) estimated from fitted CR curves. These used rank compounds, with lower DC values indicating greater potency. However, data often exhibit bi-phasic poly-phasic relationships, making standard...
Abstract Methionine, through S-adenosylmethionine, activates multifaceted growth programs where ribosome biogenesis, carbon metabolism, amino acid and nucleotide biosynthesis are induced. This program requires activity of the Gcn4 transcription factor (called ATF4 in mammals), which enables metabolic precursor supply essential for anabolism. Here, we discover how protein is induced by methionine, despite conditions high translation induction mechanism independent transcription, as well...