A5019960808- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Plant Reproductive Biology
- Biochemical and Molecular Research
- Fungal Infections and Studies
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Lipid metabolism and biosynthesis
- Calcium signaling and nucleotide metabolism
- Plant-Microbe Interactions and Immunity
- Artificial Intelligence in Healthcare
- HIV Research and Treatment
- Antimicrobial Resistance in Staphylococcus
- Genomics and Chromatin Dynamics
- ATP Synthase and ATPases Research
- Folate and B Vitamins Research
- Genetics, Bioinformatics, and Biomedical Research
- Cancer therapeutics and mechanisms
- Gene expression and cancer classification
- Antifungal resistance and susceptibility
- interferon and immune responses
- Autophagy in Disease and Therapy
Brigham and Women's Hospital
2016-2024
Harvard University
2016-2024
University of California, Berkeley
2007-2012
QB3
2008-2010
University of Chicago
2000
Very long chain lipids contribute to the hydrophobic cuticle on surface of all land plants and are an essential component extracellular pollen coat in Brassicaceae. Mutations Arabidopsis CER genes eliminate very from and, some cases, coat. In Arabidopsis, loss can disrupt interactions with stigma, inhibiting hydration causing sterility. We have positionally cloned CER6 demonstrate that a wild-type copy complements cer6-2 defect. addition, we identified fertile, intragenic suppressor,...
The pollen extracellular matrix contains proteins mediating species specificity and components needed for efficient pollination. We identified all >10 kilodaltons in the Arabidopsis coating showed that most of corresponding genes reside two genomic clusters. One cluster encodes six lipases, whereas other lipid-binding oleosin genes, including GRP17 , a gene promotes Individual oleosins exhibit extensive divergence between ecotypes, but entire remains intact. Analysis syntenic region...
Induction of lipid-laden foamy macrophages is a cellular hallmark tuberculosis (TB) disease, which involves the transformation infected phagolysosomes from site killing into nutrient-rich replicative niche. Here, we show that terpenyl nucleoside shed Mycobacterium tuberculosis, 1-tuberculosinyladenosine (1-TbAd), caused lysosomal maturation arrest and autophagy blockade, leading to lipid storage in M1 macrophages. Pure 1-TbAd, or infection with nucleoside-producing M. intralysosomal...
The macrophage is the primary host cell for fungal pathogen Histoplasma capsulatum during mammalian infections, yet little known about genes required intracellular replication in host. Since ability to scavenge iron from important virulence of most pathogens, we investigated role acquisition H. pathogenesis. acquires through action ferric reductases and production siderophores, but responsible these activities their have not been determined. We identified a discrete set co-regulated whose...
Significance Mycobacterium is a family of bacteria that includes number dangerous pathogens. Arresting the growth mycobacteria may be possible through disruption control points regulate cell envelope biosynthesis. We demonstrate smegmatis possesses spatially distinct biosynthetic membrane domain enriched in polar region cell. This act as an organizing center to spatiotemporally coordinate activities during live cells. Thus, our findings provide important insight into potential regulatory...
Tuberculosis is the leading killer among infectious diseases worldwide. Increasing multidrug resistance has prompted new approaches for tuberculosis drug development, including targeted inhibition of virulence determinants and signaling cascades that control many downstream pathways. We used a multisystem approach to determine effects potent small-molecule inhibitor essential
During industrialization, humans have been exposed to increasing numbers of foreign chemicals. Failure the immune system tolerate drugs, cosmetics, and other skin products causes allergic contact dermatitis, a T cell-mediated disease with rising prevalence. Models αβ cell response emphasize receptor (TCR) peptide-MHC complexes, but this model cannot readily explain activation by most dermatitis allergens, which are nonpeptidic molecules. We tested whether CD1a, an abundant MHC I-like protein...
The CD1 system binds lipid antigens for display to T cells. Here, we solved lipidomes the four human antigen-presenting molecules, providing a map of self-lipid display. Answering basic question, detection >2,000 CD1-lipid complexes demonstrates broad presentation self-sphingolipids and phospholipids. Whereas peptide are chemically processed, many lipids presented in an unaltered form. However, each type protein differentially edits self-lipidome show distinct capture motifs based on length...
Cystathionine-β-synthase (CBS) deficiency is a human genetic disease causing homocystinuria, thrombosis, mental retardation, and suite of other devastating manifestations. Early detection coupled with dietary modification greatly reduces pathology, but the response to treatment differs allele CBS. A better understanding relationship between allelic variants protein function will improve both diagnosis treatment. To this end, we tested 84 CBS alleles previously sequenced from patients...
Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4–7%, with the overall developing increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERα+) and represent indicators and/or precursor low grade ERα+ tumors. Therefore, molecular profiles offer insights into earliest changes in epithelium, rendering it susceptible oncogenic transformation. In this study, women were selected who diagnosed ductal or lobular AH, but no prior...
Salmonella species are among the world’s most prevalent pathogens. Because cell wall interfaces with host, we designed a lipidomics approach to reveal pathogen-specific compounds. Among molecules differentially expressed between Paratyphi and S. Typhi, focused on lipids that enriched in because it causes typhoid fever. We discovered previously unknown family of trehalose phospholipids, 6,6′-diphosphatidyltrehalose (diPT) 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is...
The intracellular membrane domain (IMD) is a laterally discrete region of the mycobacterial plasma membrane, enriched in subpolar rod-shaped cell. Here, we report genome-wide transposon sequencing to discover controllers compartmentalization Mycobacterium smegmatis. putative gene
The intracellular membrane domain (IMD) in mycobacteria is a spatially distinct region of the plasma with diverse functions. Previous comparative proteomic analysis IMD suggested that menaquinone biosynthetic enzymes are associated this domain. In present study, we determined subcellular site these using sucrose density gradient fractionation. We found last two enzymes, methyltransferase MenG, and reductase MenJ, Mycobacterium smegmatis. MenA, prenyltransferase mediates first...
Mycobacterium tuberculosis (Mtb) releases the unusual terpene nucleoside 1-tuberculosinyladenosine (1-TbAd) to block lysosomal function and promote survival in human macrophages. Using conventional approaches, we found that genes Rv3377c Rv3378c, but not Rv3376, were necessary for 1-TbAd biosynthesis. Here, introduce linear models mass spectrometry (limms) software as a next-generation lipidomics tool study essential functions of lipid biosynthetic enzymes on whole-cell basis. limms,...
Millions of people harbor latent infections the fungus Histoplasma capsulatum . Such persistent represent a stalemate between mechanisms virulence and immune response. The differing responses inbred mouse strains to same pathogen reflect variation in genes that control outcome infection. Here we show 250-fold difference H. susceptibility is attributable genotype at MHC H2 locus. Gene expression analysis varying only locus identified genotype-specific genotype-independent signatures,...