A5081018257- Peptidase Inhibition and Analysis
- Advanced Proteomics Techniques and Applications
- Click Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Chemical Synthesis and Analysis
- Cell death mechanisms and regulation
- Genomics and Phylogenetic Studies
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Sex and Gender in Healthcare
- Bioinformatics and Genomic Networks
- Genomics and Chromatin Dynamics
- Cardiac electrophysiology and arrhythmias
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- CRISPR and Genetic Engineering
- Cerebrovascular and genetic disorders
- Protease and Inhibitor Mechanisms
- Gender Roles and Identity Studies
- Machine Learning in Bioinformatics
- Biotin and Related Studies
University of California, Los Angeles
2018-2025
Icahn School of Medicine at Mount Sinai
2024
Broad Center
2020
Chemoproteomics has enabled the rapid and proteome-wide discovery of functional, redox-sensitive, ligandable cysteine residues. Despite widespread adoption considerable advances in both sample-preparation workflows MS instrumentation, chemoproteomics experiments still typically only identify a small fraction all cysteines encoded by human genome. Here, we develop an optimized workflow that combines enhanced peptide labeling with single-pot, solid-phase-enhanced (SP3) to improve recovery...
An activation-based high throughput screening platform enables inhibitor discovery for procaspase-10.
Article18 February 2021Open Access Source DataTransparent process From chemoproteomic-detected amino acids to genomic coordinates: insights into precise multi-omic data integration Maria F Palafox orcid.org/0000-0002-4752-953X Department of Human Genetics, David Geffen School Medicine, UCLA, Los Angeles, CA, USA Biological Chemistry, Pathology and Laboratory Search for more papers by this author Heta S Desai Molecular Biology Institute, Valerie A Arboleda Corresponding Author [email...
Cysteine chemoproteomics studies provide proteome-wide portraits of the ligandability or potential ‘druggability’ thousands cysteine residues. Consequently, these are enabling resources for closing druggability gap, namely achieving pharmacological manipulation ~99% human proteome that remains untargeted by FDA approved small molecules. Recent interactive dataset repositories, such as OxiMouse and SLCABPP, have enabled users to interface more readily with studies1,2. However, databases...
Abstract The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B ( KAT6B , a.k.a. MORF MYST4 ) results several interrelated syndromes including Say‐Barber‐Biesecker‐Young‐Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel variants. These patients exhibit a range of clinical phenotypes intellectual disability, mobility language difficulties, craniofacial dysmorphology, skeletal anomalies. Given the features...
Cysteine chemoproteomics studies provide proteome-wide portraits of the ligandability or potential ‘druggability’ thousands cysteine residues. Consequently, these are enabling resources for closing druggability gap, namely achieving pharmacological manipulation ~99% human proteome that remains untargeted by FDA approved small molecules. Recent interactive dataset repositories, such as OxiMouse and SLCABPP, have enabled users to interface more readily with studies1,2. However, databases...
<p>We report a new cysteine chemoproteomic method, termed SP3-FAIMS chemoproteomics, which enables rapid and high coverage analysis of the human cysteinome. By combining enhanced biotinylation with SP3 sample decontamination FAIMS online fraction, we identified in aggregate 34,225 unique cysteines found on 7,243 proteins. Showcasing versatility our integration isoTOP-ABPP workflow enabled throughput discovery labelled by electrophilic compounds. </p>
Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of vascular cognitive impairment dementia. A genetic arteriolosclerotic disease, molecular mechanisms driving brain degeneration decline remain unclear. With goal discovery disease-relevant biological perturbations in CADASIL, we used machine learning approaches to extract proteomic disease signatures from large-scale proteomics generated plasma...
ABSTRACT Caspases are a family of highly homologous cysteine proteases that play critical roles in inflammation and apoptosis. Small molecule inhibitors useful tools for studying caspase biology, complementary to genetic approaches. However, achieving inhibitor selectivity individual members this enzyme remains major challenge developing such tool compounds. Prior studies have revealed one strategy tackle gap is target the precursor or zymogen forms caspases, which share reduced structural...
ABSTRACT The integration of proteomic, transcriptomic, and genetic-variant annotation data will improve our understanding genotype-phenotype associations. Due, in part, to challenges associated with accurate inter-database mapping, such multi-omic studies have not extended chemoproteomics, a method that measure the intrinsic reactivity potential ‘druggability’ nucleophilic amino acid side chains. Here, we evaluated two mapping approaches match chemoproteomic-detected cysteine lysine residues...
We report a new cysteine chemoproteomic method, termed SP3-FAIMS chemoproteomics, which enables rapid and high coverage analysis of the human cysteinome. By combining enhanced biotinylation with SP3 sample decontamination FAIMS online fraction, we identified in aggregate 34,225 unique cysteines found on 7,243 proteins. Showcasing versatility our integration isoTOP-ABPP workflow enabled throughput discovery labelled by electrophilic compounds.