A5102426146- Cellular transport and secretion
- Fungal and yeast genetics research
- Microtubule and mitosis dynamics
- Antibiotic Resistance in Bacteria
- Biochemical and Molecular Research
- Gut microbiota and health
- Genetic Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- Diet and metabolism studies
- Drug Transport and Resistance Mechanisms
- HIV/AIDS drug development and treatment
- Genomics and Chromatin Dynamics
- Endoplasmic Reticulum Stress and Disease
- Tryptophan and brain disorders
- Genomics and Phylogenetic Studies
- Plant Reproductive Biology
- interferon and immune responses
- Epigenetics and DNA Methylation
- 14-3-3 protein interactions
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Bacterial Infections and Vaccines
- Nitric Oxide and Endothelin Effects
- Chromosomal and Genetic Variations
Roche (United States)
2023
University of Michigan
2006-2020
University of California, Berkeley
2009-2015
University of Iowa
2006-2008
IL-22 is induced by aryl hydrocarbon receptor (AhR) signaling and plays a critical role in gastrointestinal barrier function through effects on antimicrobial protein production, mucus secretion, epithelial cell differentiation proliferation, giving it the potential to modulate microbiome these direct indirect effects. Furthermore, can turn influence production synthesis of L-tryptophan (L-Trp)-derived AhR ligands, creating prospect host-microbiome feedback loop. We evaluated impact may have...
Guanine nucleotides are required for growth and viability of cells due to their structural role in DNA RNA, regulatory roles translation, signal transduction, cell division. The natural antibiotic mycophenolic acid (MPA) targets the rate-limiting step
Dynamic microtubules facilitate chromosome arrangement before anaphase, whereas during anaphase microtubule stability assists separation. Changes in dynamics at the metaphase–anaphase transition are regulated by Cdk1. Cdk1-mediated phosphorylation of Sli15/INCENP promotes preanaphase preventing chromosomal passenger complex (CPC; Sli15/INCENP, Bir1/Survivin, Nbl1/Borealin, Ipl1/Aurora) association with spindles. However, whether Cdk1 has sole control over dynamics, and how CPC–microtubule...
Lipoprotein diacylglyceryl transferase (Lgt) catalyzes the first step in biogenesis of Gram-negative bacterial lipoproteins which play crucial roles growth and pathogenesis. We demonstrate that Lgt depletion a clinical uropathogenic Escherichia coli strain leads to permeabilization outer membrane increased sensitivity serum killing antibiotics. Importantly, we identify G2824 as first-described inhibitor potently inhibits biochemical activity vitro is bactericidal against wild-type...
Vac8p, an armadillo (ARM) repeat protein, is required for multiple vacuolar processes. It functions in vacuole inheritance, cytoplasm‐to‐vacuole protein targeting pathway, formation of the nucleus–vacuole junction and vacuole–vacuole fusion. These each utilize a distinct Vac8p‐binding partner. Here, we report additional Vac8p function: caffeine resistance. We show that function resistance mediated via newly identified partner, Tco89p. The interaction between binding partner requires...
Casein kinase 1δ (CK1δ) family members associate with microtubule-organizing centers (MTOCs) from yeast to humans, but their mitotic roles and targets have yet be identified. We show here that budding CK1δ, Hrr25, is a γ-tubulin small complex (γTuSC) binding factor. Moreover, Hrr25's association γTuSC depends on its activity noncatalytic central domain. Loss of Hrr25 resulted in assembly unusually long cytoplasmic microtubules defects spindle positioning, consistent regulation γTuSC-mediated...
Despite increasing evidence suggesting that antibiotic heteroresistance can lead to treatment failure, the significance of this phenomena in clinic is not well understood, because many clinical susceptibility testing approaches lack resolution needed reliably classify heteroresistant strains. Here we present G0790, a new globomycin analog and potent inhibitor Escherichia coli type II signal peptidase LspA. We demonstrate addition previously known mechanisms resistance LspA inhibitors,...
Vac8p is a multifunctional yeast protein involved in several distinct vacuolar events including vacuole inheritance, homotypic fusion, nucleus–vacuole junction formation and the cytoplasm to targeting pathway. associates with membrane via myristoylation palmitoylation. has three putative palmitoylation sites, at Cys 4, 5 7. Here, we show that each of these cysteines may serve as site. Palmitoylation 7 alone provides partial function Vac8p, whereas either 4 or sufficient for function. In...
Protein kinase CK2 is one of the most conserved kinases in eukaryotic cells and plays essential roles diverse processes. While we know that a role(s) cell division, our understanding how regulates cycle progression limited. In this study, revealed regulatory role for kinetochore function. The multi-protein complex assembles on centromere chromosome functions to attach chromosomes spindle microtubules. To faithfully segregate maintain genomic integrity, tightly regulated by multiple...
Acinetobacter baumannii is a highly pathogenic Gram-negative bacterium that causes severe infections with very high fatality rates. A. infection triggers innate as well adaptive immunity, however, our understanding of the inflammatory factors secreted by alarm immune system remains limited. In this study, we report lab adapted and clinical strains secrete an bioactive factor which activates TLR2, leading to canonical IRAK4-dependent NF-κB signaling production pro-inflammatory cytokines...
ABSTRACT Inosine 5′-monophosphate dehydrogenase (IMPDH), known as GuaB in bacteria, catalyzes the rate-limiting step de novo guanine biosynthesis and is conserved from humans to bacteria. We developed a series of potent inhibitors that selectively target over its human homolog. Here, we show these are bactericidal, generate phenotypic signatures distinct other antibiotics, elicit different time-kill kinetics regulatory responses two important Gram-negative pathogens: Acinetobacter baumannii...
Acinetobacter baumannii is a clinically important, predominantly health care–associated gram-negative bacterium with high rates of emerging resistance worldwide. Given the urgent need for novel antibacterial therapies against A. , we focused on inhibiting lipoprotein biosynthesis, pathway that essential envelope biogenesis in bacteria. The natural product globomycin, which inhibits type II signal peptidase prolipoprotein (LspA), ineffective wild-type clinical isolates due to its poor...
Aspergillus fumigatus is one of the major causes invasive pulmonary aspergillosis in immunocompromised patients. Novel antifungal therapy urgent need due to emerging resistance and adverse toxicity current drugs. Gene products that are essential for viability during infection attractive drug targets. To characterize these genes vivo we developed a Tet-Off gene expression system A. fumigatus, whereby administration doxycycline resulted down regulation whose under control promoter. We tested...
Abstract Ruminococcus gnavus is a prevalent human gut commensal bacterium with known roles in intestinal mucus degradation, including by catabolism of the terminal mucin sugar sialic acid. While R. not considered pathogen, overabundance this species correlated Inflammatory Bowel Disease (IBD), and its acid metabolism may play role dysbiotic state. Interestingly, liberation mucin-bound yields distinct product 2,7-anhydro- N -acetylneuraminic (2,7-anhydro-Neu5Ac), contrast to other...
While much has been learned about the mechanisms by which clathrin‐coated vesicles are formed during endocytosis, less is known how their formation regulated. Here, we investigate role of protein phosphorylation in regulation clathrin‐mediated endocytosis. We found that both budding yeast and mammalian cells casein kinase 1 δ/ε , Hrr25, associates with regulates endocytic machinery. In yeast, Hrr25 recruited to patches early pathway C‐terminus Eps15‐like protein, Ede1, where it...
During cell division cytoplasmic organelles are actively distributed to the new daughter cells. This process is tightly controlled both spatially and temporally. In yeast S. cerevisiae, myosin V motor, Myo2p required for inheritance of several organelles. The itineraries these partially overlap, yet not identical. Different cargoes bind distinct regions within cargo‐binding domain Myo2. Moreover, organelle‐specific receptors attach motor. existence suggests that their regulation may account...
Abstract Lipoprotein diacylglyceryl transferase (Lgt) catalyzes the first step in biogenesis of Gram-negative bacterial lipoproteins which play crucial roles growth and pathogenesis. We demonstrate that Lgt depletion a clinical uropathogenic Escherichia coli strain leads to permeabilization outer membrane increased sensitivity serum killing antibiotics. Importantly, we identify ever described inhibitors potently inhibit biochemical activity vitro are bactericidal against wild-type...