A5070253714- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- HIV Research and Treatment
- Prostate Cancer Treatment and Research
- Bacteriophages and microbial interactions
- Protein Degradation and Inhibitors
- vaccines and immunoinformatics approaches
- Adipose Tissue and Metabolism
- Ubiquitin and proteasome pathways
- Muscle metabolism and nutrition
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Machine Learning in Bioinformatics
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Protein Structure and Dynamics
- Genomics and Phylogenetic Studies
- Hepatitis B Virus Studies
- Muscle Physiology and Disorders
- Biochemical and Structural Characterization
- Virology and Viral Diseases
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- Melanoma and MAPK Pathways
- Cancer, Lipids, and Metabolism
Exagenica (United Kingdom)
2023
Sanford Burnham Prebys Medical Discovery Institute
2010-2020
Discovery Institute
2007-2020
Rancho BioSciences (United States)
2019
Scripps Research Institute
2013-2017
University of California, San Diego
2013
Institute for Medical Research
2009
UConn Health
2008
State Research Center of Virology and Biotechnology VECTOR
1990-2007
Purdue University West Lafayette
2007
Highlights•Immunization protocols for rapid and consistent generation of autologous tier 2 nAbs•Germinal center responses predict correlate with HIV nAbs after immunization•Env protein design curtails to the non-neutralizing V3-loop epitope•Subcutaneous extended immunogen delivery enhances nAb generationSummaryThe development stabilized recombinant envelope trimers that mimic virion surface molecule has increased enthusiasm a neutralizing antibody (nAb)-based vaccine. However, there is...
Most known organisms encode proteases that are crucial for constitutive proteolytic events. In the present paper, we describe a method to define these events in proteomes from Escherichia coli humans. The takes advantage of specific N-terminal biotinylation protein samples, followed by affinity enrichment and conventional LC (liquid chromatography)-MS/MS (tandem mass spectrometry) analysis. is simple, uses easily obtainable reagents, applicable most proteomics facilities. As proof principle,...
Beyond the well-known role of proteolytic machinery in protein degradation and turnover, many specialized proteases play a key various regulatory processes. Thousands highly specific events are associated with normal pathological conditions, including bacterial viral infections. However, information about individual is dispersed over multiple publications not easily available for large-scale analysis. CutDB one first systematic efforts to build an accessible collection documented natural...
The ubiquitin ligase Siah2 has been shown to regulate prolyl hydroxylase 3 (PHD3) stability with concomitant effect on HIF-1alpha availability. Because is implicated in tumorigenesis and metastasis, we used SW1 mouse melanoma cells, which develop primary tumors a propensity metastasize, syngeneic model assess possible role for these processes. Inhibiting activity by expressing peptide designed outcompete association of Siah2-interacting proteins reduced metastasis through without affecting...
Significance Specificity-determining positions (SDPs) account for distinctions in function across a protein family. Many theories on the evolution of functional specificity have led to approaches predicting SDPs silico, but large experimental datasets allowing statistical assignment are lacking. Here, matrix metalloproteinases elucidated by querying proteolytic efficiency eight metalloproteinases, representing three phylogenetic branches, an extended and diverse substrate space. More than...
The discovery of broadly neutralizing antibodies (bNAbs) has provided an enormous impetus to the HIV vaccine research and entire immunology. bNAber database at http://bNAber.org provides open, user-friendly access detailed data on rapidly growing list bNAbs, including neutralization profiles, sequences three-dimensional structures (when available). It also extensive visualization analysis tools, such as heatmaps analyse well structure sequence viewers correlate bNAbs properties with...
The identification of natural substrates and their cleavage sites is pivotal to defining proteolytic pathways. Here we report a novel strategy for the signature events based on quantitative proteomics. Lysine residues in proteins are blocked by guanidination so that free N-terminals can be labeled with amine-specific iTRAQ reagents. nature reagents allows us distinguish newly formed treatment (neoepitopes) from original proteins. Proteins digested trypsin analyzed using MALDI-TOF/TOF mass...
The transcription factor ATF2 has been shown to attenuate melanoma susceptibility apoptosis and promote its ability form tumors in xenograft models. To directly assess ATF2's role development, we crossed a mouse model (NrasQ61K::Ink4a−/−) with mice expressing transcriptionally inactive of melanocytes. In contrast 7/21 the NrasQ61K::Ink4a−/− mice, only 1/21 mutant melanocytes developed melanoma. Gene expression profiling identified higher MITF primary ATF2. downregulation by was confirmed...
Nearly 50 congenital disorders of glycosylation (CDG) are known, but many patients biochemically diagnosed with CDG do not have mutations in known genes. Here, we describe a 16-year-old male who was born microcephaly, developed intellectual disability, gastroesophageal reflux and seizure disorder. We identified de novo variant the X-linked SSR4 gene which encodes protein heterotetrameric translocon-associated (TRAP) complex. The c.316delT causes p.F106Sfs*53 also reduces expression other...
The Proteolysis MAP (PMAP, http://www.proteolysis.org) is a user-friendly website intended to aid the scientific community in reasoning about proteolytic networks and pathways. PMAP comprised of five databases, linked together one environment. foundation ProteaseDB SubstrateDB, are driven by an automated annotation pipeline that generates dynamic 'Molecule Pages', rich molecular information. also contains two annotated databases focused on function; CutDB has information more than 5000...
Limited or regulatory proteolysis plays a critical role in many important biological pathways like blood coagulation, cell proliferation, and apoptosis. A better understanding of mechanisms that control this process is required for discovering new proteolytic events developing inhibitors with potential therapeutic value. Two features determine the susceptibility peptide bonds to are sequence vicinity scissile bond structural context which displayed. In study, we assessed statistical...
Studies showing reduced PKCζ expression or enzymatic activity in different types of human cancers support the clinical relevance as a tumor suppressor. However, vivo role and its mechanisms action prostate cancer remain unclear. Here we demonstrate that genetic inactivation mice results invasive carcinoma context phosphatase tensin homolog deficiency. Bioinformatic analysis gene-expression sets revealed increased c-Myc transcriptional PKCζ-inactive cells, which correlated with cell growth,...
The effects of caloric restriction (CR) on in vivo muscle mitochondrial function humans are controversial. We evaluated and associated transcriptional profiles nonobese after 12 months CR. Individuals from an ancillary study the CALERIE 2 randomized controlled trial were assessed at baseline a 25% CR or ad libitum (control) diet. was performed Pennington Biomedical Research Center Baton Rouge, LA. Study participants included 51 (34 female subjects, 25 to 50 years age) healthy individuals 1...
Some individuals with type 2 diabetes do not reap metabolic benefits from exercise training, yet the underlying mechanisms of training response variation are largely unexplored. We classified (n = 17) as nonresponders 6) or responders 11) based on changes in phosphocreatine (PCr) recovery rate after 10 weeks aerobic training. aimed to determine whether PCr was marked by distinct epigenomic profiles muscle prior training.PCr an indicator vivo mitochondrial function vastus lateralis...
Resistance to androgen receptor (AR) antagonists is a significant problem in the treatment of castration-resistant prostate cancers (CRPC). Identification mechanisms by which CRPCs evade deprivation therapies (ADT) critical develop novel therapeutics. We uncovered that rely on BRD4-HOXB13 epigenetic reprogramming for androgen-independent cell proliferation. Mechanistically, BRD4, member BET bromodomain family, epigenetically promotes HOXB13 expression. Consistently, genetic disruption or...
Androgen depletion in humans leads to significant atrophy of the limb muscles. However, pathways by which androgens regulate muscle mass are unclear. Our laboratory previously showed that mitochondrial degradation was related induction autophagy and degree following androgen depletion, implying decreased quality contributes atrophy. To increase our understanding androgen-sensitive regulating quality, total RNA from tibialis anterior sham castrated mice subjected microarray analysis. Using...
The metabolic stress placed on skeletal muscle by aerobic exercise promotes acute and long-term health benefits in part through changes gene expression. However, the transducers that mediate altered expression signatures have not been completely elucidated. Regulated development DNA damage 1 (REDD1) is a stress-induced protein whose transiently increased following exercise. role of this induction remains unclear. Because REDD1 other model systems, we sought to determine whether signature...