A5050888666- Antibiotic Resistance in Bacteria
- Alzheimer's disease research and treatments
- Bacterial biofilms and quorum sensing
- Aquaculture disease management and microbiota
- Bacteriophages and microbial interactions
- Immune Cell Function and Interaction
- Zebrafish Biomedical Research Applications
- Bacterial Genetics and Biotechnology
- Genomics and Phylogenetic Studies
- Tuberculosis Research and Epidemiology
- T-cell and B-cell Immunology
- Vibrio bacteria research studies
- Cholinesterase and Neurodegenerative Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Nuclear Receptors and Signaling
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Tryptophan and brain disorders
- Neuroendocrine regulation and behavior
- Bacillus and Francisella bacterial research
- Mycobacterium research and diagnosis
- Bacterial Identification and Susceptibility Testing
- Biochemical and Molecular Research
- Rabies epidemiology and control
- Biosimilars and Bioanalytical Methods
- Erythrocyte Function and Pathophysiology
Massachusetts General Hospital
2009-2024
Harvard University
2003-2024
Broad Institute
2011-2024
University of Massachusetts Boston
2023
Dimagi (United States)
2023
Genomics offered the promise of transforming antibiotic discovery by revealing many new essential genes as good targets, but results fell short promise. While numerous factors contributed to disappointing yield, one factor was that for a bacterial species were often defined based on single or limited number strains grown under in vitro laboratory conditions. In fact, essentiality gene can depend both genetic background and growth condition. We thus developed strategy more rigorously defining...
<b>Objective: </b> Hemorrhage related to cerebral amyloid angiopathy (CAA) appears occur through a multistep pathway that includes deposition of β-amyloid in vessels and specific vasculopathic changes the amyloid-laden vessels, such as cracking vessel wall. Recent reports suggest positive association between CAA-related hemorrhage both apolipoprotein E (APOE) ϵ4 allele and, unexpectedly, APOE ϵ2 allele. Unlike ϵ4, does not appear act increased deposition. We therefore sought determine...
ABSTRACT Zebrafish ( Danio rerio ) have a number of strengths as host model for infection, including genetic tractability, vertebrate immune system similar to that mammals, ease and scale laboratory handling, which allows analysis with reasonable throughput, transparency, facilitates visualization the infection. With these advantages in mind, we examined whether zebrafish could be used study Pseudomonas aeruginosa pathogenesis found infection embryos live P. (PA14 or PAO1) by microinjection...
alpha2-Macroglobulin (A2M) is a proteinase inhibitor found in association with senile plaques (SP) Alzheimer's disease (AD). A2M has been implicated biochemically binding and degradation of the amyloid beta (Abeta) protein which accumulates SP. We studied relationship between common polymorphism, Val1000 (GTC)/Ile1000 (ATC), occurs near thiolester active site molecule. In an initial exploratory data set (90 controls 171 disease) we noted increased frequency G/G genotype from 0.07 to 0.12....
Infection with the bacterial pathogen Mycobacterium tuberculosis imposes an enormous burden on global public health. New antibiotics are urgently needed to combat pandemic; however, development of new small molecules is hindered by a lack validated drug targets. Here, we describe identification 4,6-diaryl-5,7-dimethyl coumarin series that kills M. inhibiting fatty acid degradation protein D32 (FadD32), enzyme required for biosynthesis cell-wall mycolic acids. These substituted inhibitors...
ABSTRACT Two-component sensors are widely used by bacteria to sense and respond the environment. Pseudomonas aeruginosa has one of largest sets two-component known in bacteria, which likely contributes its unique ability adapt multiple environments, including human host. Several these sensors, such as GacS RetS, have been shown play roles virulence rodent infection models. However, role function majority remain unknown. Danio rerio is a recently characterized model host for...
Tuberculosis is a global threat, with ~10 million yearly active cases. Many more people, however, live “latent” infection, where Mycobacterium tuberculosis survives in non-replicative form. When latent bacteria activate and regrow, they elicit immune responses result significant host damage. Replicating non-growing bacilli can co-exist; are considerably less sensitive to antibiotics, thus complicating treatment by necessitating long durations. Here, we sought identify genes important for...
is increasingly recognized for causing infections that are notoriously difficult to treat, owing its large arsenal of intrinsic antibiotic resistance mechanisms. Tools the genetic manipulation pathogen critical enabling a better understanding
Abstract Ag-specific T cell recognition is mediated through direct interaction of clonotypic TCRs with complexes formed between Ag-presenting molecules and their bound ligands. Although characterized in substantial detail for class I II MHC encoded molecules, the molecular interactions responsible TCR CD1 lipid glycolipid are not yet well understood. Using a panel epitope-specific Abs site-specific mutants CD1b molecule, we showed that occur on membrane distal aspects molecule over α1 α2...
The apolipoprotein E epsilon 4 (ApoE 4) allele is associated with an increased risk for development of Alzheimer disease (AD). We hypothesized that polymorphisms in proteins interact ApoE also might have impact on the likelihood AD developing. examined a polymorphism gene low-density lipoprotein receptor-related protein (LRP), because LRP major receptor brain mediates binding and degradation secreted Kunitz protease inhibitor forms amyloid precursor protein.The genotypes 2 groups were...
ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that capable of causing both acute and chronic infections. P. virulence subject to sophisticated regulatory control by two-component systems enable it sense respond environmental stimuli. We recently reported the sensor KinB regulates in infection. Furthermore, acute-virulence-associated phenotypes such as pyocyanin production, elastase motility a manner independent its kinase activity. Here we show through global sigma factor...
Xenografts of the hematopoietic system are extremely useful as disease models and for translational research. Zebrafish xenografts have been widely used to monitor blood cancer cell dissemination homing due optical clarity embryos larvae, which allow unrestricted in vivo visualization migratory events. Here, we developed a xenotransplantation technique that transiently generates hundreds tissue chimeric by transplanting murine bone marrow cells into zebrafish blastulae. In contrast previous...
Bacterial toxins have evolved successful strategies for coopting host proteins to access the cytosol of cells. Anthrax lethal factor (LF) enters through pores in endosomal membrane formed by anthrax protective antigen. Although vitro models using planar lipid bilayers shown that translocation can occur absence cellular factors, recent studies intact endosomes indicate factors are required environment. In this study, we describe a high-throughput shRNA screen identify toxin-induced cell...
Lymphoid cells of the vertebrate immune system rely on factors in non-homologous end-joining (NHEJ) DNA repair pathway to form signal joints during V(D)J recombination. Unlike other reactions, joint formation is a specialized case NHEJ that also requires lymphoid-specific RAG proteins. Whether recombination Mre11-Rad50-Nbs1 complex remains an open question, as null mutations any member are lethal mammals. However, Saccharomyces cerevisiae strains carrying components homologous...