A5086478181- Metabolism, Diabetes, and Cancer
- Diabetes Treatment and Management
- Salmonella and Campylobacter epidemiology
- Escherichia coli research studies
- Vibrio bacteria research studies
- Microtubule and mitosis dynamics
- Gut microbiota and health
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Viral gastroenteritis research and epidemiology
- Pancreatic function and diabetes
- Plant Molecular Biology Research
- Neurological and metabolic disorders
- Diet and metabolism studies
- Bacteriophages and microbial interactions
- Bacterial Genetics and Biotechnology
- Peroxisome Proliferator-Activated Receptors
- RNA and protein synthesis mechanisms
- Liver Disease Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Neuroscience of respiration and sleep
- Complement system in diseases
- Fetal and Pediatric Neurological Disorders
- Skin and Cellular Biology Research
- Clostridium difficile and Clostridium perfringens research
- Hippo pathway signaling and YAP/TAZ
Brigham and Women's Hospital
2022-2025
Harvard University
2022-2025
University of St Andrews
2005-2021
Massachusetts Institute of Technology
2016-2020
Howard Hughes Medical Institute
2016-2020
Duke University
2016
Carnegie Mellon University
2011-2014
Western University
2014
Victoria Hospital
2002-2007
University of Glasgow
1991-2002
Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and tuberculosis. All mycobacteriophages characterized to date dsDNA tailed phages, have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, although sixty-two genomes been sequenced comparatively analyzed, these likely represent only a small portion of the mycobacteriophage population at large. Here we report isolation, sequencing comparative genomic...
Host bottlenecks prevent many infections before the onset of disease by eliminating invading pathogens. By monitoring diversity a barcoded population diarrhea causing bacterium Citrobacter rodentium during colonization its natural host, mice, we determine number cells that found infection establishing replicative niche. In female mice size pathogen's founding scales with dose and is controlled severe yet slow-acting bottleneck. Reducing stomach acid or changing host genotype modestly relaxes...
We have conducted a narrative review based on structured search strategy, focusing the effects of metformin progression non-diabetic hyperglycemia to clinical type 2 diabetes mellitus. The principal trials that demonstrated significantly lower incidence in at-risk populations randomized (mostly with impaired glucose tolerance [IGT]) were published mainly from 1999 2012. Metformin reduced 3-year risk by -31% phase Diabetes Prevention Program (DPP), vs. -58% for intensive lifestyle...
Summary C‐reactive protein (CRP) is the prototypic acute‐phase in man which performs innate immune functions. CRP‐mediated phagocytosis may be indirect, through activation of complement and receptors, or direct, receptors for Fc portion immunoglobulin G (IgG; FcγRs) even a putative CRP‐specific receptor. No strong evidence has been shown to indicate responsible signalling responses. Using BIAcore technology, we confirm that CRP binds directly extracellular FcγRI with threefold higher...
Previous work from our lab suggests that a group of interdependent assembly factors (A(3) factors) is necessary to create early, stable preribosomes. Many these proteins bind at or near internal transcribed spacer 2 (ITS2), but in their absence, ITS1 not removed rRNA, suggesting long-range communication between two spacers. By comparing the nonessential Nop12 and Pwp1, we show misfolding rRNA sufficient perturb early steps biogenesis, it lack A(3) results turnover Deletion NOP12...
Murine models are often used to study the pathogenicity and dissemination of enteric pathogen Salmonella enterica serovar Typhimurium. Here, we quantified S. Typhimurium population dynamics in mice using STAMPR analytic pipeline a highly diverse S . barcoded library containing ∼55,000 unique strains distinguishable by genomic barcodes enumerating founding populations deciphering routes spread mice. We found that severe bottleneck allowed only one million cells from an oral inoculum establish...
Outbreaks of cholera are caused by the highly transmissive pathogen Vibrio cholerae . Here, a transposon screen revealed that inactivation V. motility-linked gene motV increases infant mouse intestinal colonization. Compared to wild-type , Δ mutant, which exhibits heightened motility in form constitutive straight swimming, localizes crypts earlier infection and over larger area small intestine. Aberrant localization mutant was associated with an increased number initiating infection,...
Murine models are often used to study the pathogenicity and dissemination of enteric pathogen Salmonella enterica serovar Typhimurium. Here, we quantified S . Typhimurium population dynamics in mice using STAMPR analytic pipeline a highly diverse barcoded library containing ~55,000 unique strains distinguishable by genomic barcodes enumerating founding populations deciphering routes spread mice. We found that severe bottleneck allowed only one million cells from an oral inoculum establish...
Abstract Transposon insertion sequencing (Tn-seq) is a powerful method for genome-scale forward genetics in bacteria. However, inefficient transposon delivery or stochastic loss of mutants due to population bottlenecks can limit its effectiveness. Here we have developed ‘InducTn-seq’, where an arabinose-inducible Tn5 transposase enables temporal control mini-Tn5 transposition. InducTn-seq generated up 1.2 million from single colony enterotoxigenic Escherichia coli , Salmonella typhimurium...
The natural context in which CRISPR-Cas systems are active Enterobacteriaceae has remained enigmatic. Here, we find that the Citrobacter rodentium Type I-E system is activated by oxygen-responsive transcriptional regulator Fnr anoxic mouse intestine. Since Fnr-dependent regulation predicted ~41% of cas3 orthologs, propose immunity an adaptation protects against threats arising from intestinal microbiome.
The tissue labelling of a panel monoclonal antikeratin antibodies (LL001, LL002, LL003, LP2K, BA17, LP34, CAM5.2, and LH1) recognising keratins 1, 5, 8, 10, 14, 18, 19 were investigated in frozen formalin-fixed normal skin. Antibodies LL001, LH1 found to be reactive material used study 23 basal cell carcinomas, 8 squamous 5 keratoacanthomas, Bowen's disease, 6 clear acanthomas. All these tumours demonstrated loss keratin 10 expression as by with LH1. Keratin 14 expression, was reduced but...
GTPase signal transduction pathways control cellular decision making by integrating multiple events into a single signal. The Mitotic Exit Network (MEN), Ras-like signaling pathway, integrates spatial and temporal cues to ensure that cytokinesis only occurs after the genome has partitioned between mother daughter cells during anaphase. Here we show integration does not occur at step of pathway. Rather, sequential components pathway are controlled in series different signals. signal, nuclear...
In budding yeast, alignment of the anaphase spindle along mother–bud axis is crucial for maintaining genome integrity. If becomes misaligned in mother cell compartment, cells arrest because mitotic exit network (MEN), an essential Ras-like GTPase signaling cascade, inhibited by position checkpoint (SPoC). Distinct localization patterns MEN and SPoC components mediate inhibition. Most localize to pole bodies. mispositioned due inhibition cell–restricted kinase Kin4. Here we show that a...
The Mitotic Exit Network (MEN), a budding yeast Ras-like signal transduction cascade, translates nuclear position into to exit from mitosis. Here we describe how scaffolding the MEN onto spindle pole bodies (SPB-centrosome equivalent) allows couple final stages of mitosis position. Through quantitative analysis localization components, determined relative importance signaling SPB that is delivered daughter cell (dSPB) during anaphase and remains in mother cell. Movement half nucleus bud...
Adhesion molecules are considered to have an important role in inflammatory reactions. We investigated the kinetics of ICAM-1 expression on keratinocytes and correlated this with numbers lymphocytes expressing LFA-1 dermis epidermis evolving allergic contact dermatitis In nickel-sensitive individuals, after application a nickel patch, increased was observed as early 3 h reached maximum at 48 h. The number greatest cells were be close proximity ICAM-1, thus supporting hypothesis that...