A5068117227- Alzheimer's disease research and treatments
- Oral microbiology and periodontitis research
- Tuberculosis Research and Epidemiology
- Biochemical and Molecular Research
- Click Chemistry and Applications
- Glycosylation and Glycoproteins Research
- Antifungal resistance and susceptibility
- Peptidase Inhibition and Analysis
- Antimicrobial Resistance in Staphylococcus
- Pneumocystis jirovecii pneumonia detection and treatment
- Infective Endocarditis Diagnosis and Management
- Mycobacterium research and diagnosis
- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Biosensors and Analytical Detection
- Sepsis Diagnosis and Treatment
- Neonatal and Maternal Infections
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomics and Phylogenetic Studies
- 14-3-3 protein interactions
- Biochemical and Structural Characterization
- Early Childhood Education and Development
- Identity, Memory, and Therapy
- Diabetes Treatment and Management
Stanford University
2008-2025
MaineGeneral Medical Center
2016-2019
Harvard University
2016-2019
Massachusetts General Hospital
2016-2019
Protease-activated receptor 2 (PAR2) is a central regulator of intestinal barrier function, inflammation and pain. Upregulated proteolysis PAR2-signaling are implicated in inflammatory bowel diseases (IBDs) irritable syndrome (IBS). To identify potential bacterial regulators PAR2 activity, we developed functional assay for processing used it to screen conditioned media from library diverse gut commensal microbes. We found that multiple bacteria secrete proteases cleave host PAR2. Using...
Tuberculosis (TB) is a top-ten cause of death worldwide. Successful treatment often limited by insufficient diagnostic capabilities, especially at the point care in low-resource settings. The ideal must be fast, cheap, and require minimal clinical resources while providing high sensitivity, selectivity, ability to differentiate live from dead bacteria. We describe here development luminescent, affordable sensor Hip1 (FLASH) for detecting monitoring drug susceptibility Mycobacterium...
Phenotypically distinct cellular (sub)populations are clinically relevant for the virulence and antibiotic resistance of a bacterial pathogen, but functionally different cells usually indistinguishable from each other. Herein, we introduce fluorescent activity-based probes as chemical tools single-cell phenotypic characterization enzyme activity levels in Staphylococcus aureus. We screened 1,2,3-triazole urea library to identify selective inhibitors fluorophosphonate-binding serine...
This study examines relations between early adolescent girls' well-being, achievement, and emerging identities. Variable-centered results showed that moral student identities were the strongest predictors of their whereas moral, student, physical, peer predicted well-being. Person-centered delineated four subgroups girls based on profiles well being achievement. The largest group (46%) was characterized by positive school achievement had balanced adult- peer-oriented second (35%), emotional...
Alzheimer's disease (AD)-linked protein, presenilin 1 (PS1), is present at the synapse, and knock-out of in mice leads to synaptic dysfunction. On other hand, activity was shown influence PS1-dependent generation distinct amyloid β (Aβ) species. However, precise nature these regulations remains unclear. The current study reveals novel role PS1 deciphers how vesicle-associated synaptotagmin (Syt1) modulate each functions neurons via direct activity-triggered interaction. Additionally,...
The high levels of serine (S) and threonine (T) residues within the Presenilin 1 (PS1) N-terminus in large hydrophilic loop region suggest that enzymatic function PS1/γ-secretase can be modulated by its 'phosphorylated' 'dephosphorylated' states. However, functional outcome PS1 phosphorylation significance for Alzheimer's disease (AD) pathogenesis is poorly understood. Here, comprehensive analysis using FRET-based imaging reveals activity-driven Protein Kinase A-mediated at three domains...
The bacterial genus Staphylococcus comprises diverse species that colonize the skin as commensals but can also cause infection. Previous work identified a family of serine hydrolases termed fluorophoshonate-binding (Fphs) in pathogenic bacteria aureus, one which, FphB, functions virulence factor. Using combination bioinformatics and activity-based protein profiling (ABPP), we identify homologues these enzymes related commensal epidermidis. Two S. aureus Fph were not ABPP, several candidate...
Presenilin 1 (PS1), the catalytic component of gamma secretase, associates with synaptotagmin (Syt-1). This interaction is decreased in brains patients sporadic Alzheimer's disease. However, it remains unclear how this changes during normal aging. Because aging a risk factor for disease, we sought to identify PS1 and Syt-1 association primary neurons vitro mouse brain sections ex vivo. We also tested effect on calcium dependence by treating aged KCl. found that increase their age, an more...
Abstract Tuberculosis (TB) is a top-ten cause of death worldwide. Successful treatment often limited by insufficient diagnostic capabilities, especially at the point care in low-resource settings. The ideal must be fast, cheap, and require minimal clinical resources while providing high sensitivity, selectivity, ability to differentiate live from dead bacteria. We describe here development Fast, Luminescent, Affordable Sensor Hip1 (FLASH) for diagnosis monitoring drug sensitivity...
Abstract Phenotypically distinct cellular (sub)populations are clinically relevant for the virulence and antibiotic resistance of a bacterial pathogen, but functionally different cells usually indistinguishable from each other. Herein, we introduce fluorescent activity‐based probes as chemical tools single‐cell phenotypic characterization enzyme activity levels in Staphylococcus aureus . We screened 1,2,3‐triazole urea library to identify selective inhibitors fluorophosphonate‐binding serine...
Summary The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a global health threat necessitating the development new antibiotics. Serine hydrolases (SHs) are promising class targets because their importance for synthesis mycobacterial cell envelope. We screened library small molecules containing serine-reactive electrophiles and identified narrow spectrum inhibitors M. tuberculous growth. Using these lead molecules, we performed competitive...
Abstract Serine hydrolases play important roles in signaling and human metabolism, yet little is known about the functions of these enzymes gut commensal bacteria. Using bioinformatics chemoproteomics, we identify serine Bacteroides thetaiotaomicron that are specific to Bacteroidetes phylum. Two predicted homologs protease dipeptidyl peptidase 4 (hDPP4), a key enzyme regulates insulin signaling. Functional studies reveal BT4193 true homolog hDPP4 while other misannotated proline-specific...
Abstract Serine hydrolases play important roles in signaling and human metabolism, yet little is known about the functions of these enzymes gut commensal bacteria. Using bioinformatics chemoproteomics, we identify serine Bacteroides thetaiotaomicron that are specific to Bacteroidetes phylum. Two predicted homologs protease dipeptidyl peptidase 4 (hDPP4), a key enzyme regulates insulin signaling. Functional studies reveal BT4193 true homolog hDPP4 while other misannotated proline-specific...
The increasing incidence of antibiotic-resistant Mycobacterium tuberculosis infections is a global health threat necessitating the development new antibiotics. Serine hydrolases (SHs) are promising class targets because their importance for synthesis mycobacterial cell envelope. We screened library small molecules containing serine-reactive electrophiles and identified narrow spectrum inhibitors M. tuberculous growth. Using these lead molecules, we performed competitive activity-based...