A5031762888- Salmonella and Campylobacter epidemiology
- Inflammasome and immune disorders
- Vibrio bacteria research studies
- Escherichia coli research studies
- Immune Response and Inflammation
- Viral gastroenteritis research and epidemiology
- interferon and immune responses
- Bacteriophages and microbial interactions
- Gut microbiota and health
- Bacillus and Francisella bacterial research
- Bacterial Genetics and Biotechnology
- Cell death mechanisms and regulation
- Heme Oxygenase-1 and Carbon Monoxide
- Yersinia bacterium, plague, ectoparasites research
- Immune cells in cancer
- Bacterial Infections and Vaccines
- Clostridium difficile and Clostridium perfringens research
- Cancer Research and Treatments
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- Kawasaki Disease and Coronary Complications
- SARS-CoV-2 and COVID-19 Research
- Antimicrobial Peptides and Activities
- Probiotics and Fermented Foods
- Bacterial biofilms and quorum sensing
Stanford University
2016-2025
Stratford University
2018-2023
Stanford Medicine
2008-2019
Palo Alto University
2018
Indiana University School of Medicine
2012
Bipar
2010-2011
University of Washington
2007
University of California, San Francisco
2007
Fairchild Semiconductor (United States)
2007
Science Applications International Corporation (United States)
1999
Recently, Salmonella spp. were shown to induce apoptosis in infected macrophages. The mechanism responsible for this process is unknown. In report, we establish that the Inv-Spa type III secretion apparatus target invasin SipB necessary and sufficient induction of apoptosis. Purified microinjected into macrophages led cell death. Binding studies show associates with proapoptotic protease caspase-1. This interaction results activation caspase-1, as seen its proteolytic maturation processing...
The peritoneal cavity (PerC) is a unique compartment within which variety of immune cells reside, and from macrophages (MØ) are commonly drawn for functional studies. Here we define two MØ subsets that coexist in PerC adult mice. One, provisionally called the large (LPM), contains approximately 90% unstimulated animals but disappears rapidly following lipopolysaccharide (LPS) or thioglycolate stimulation. These express high levels canonical surface markers, CD11b F4/80. second subset,...
Salmonella pathogenicity island 2 (SPI‐2) encodes a putative type III secretion system necessary for systemic infection in animals. We have investigated the transcriptional organization and regulation of SPI‐2 by creating gfp fusions throughout entire gene cluster. These demonstrated that genes encoding structural, regulatory previously uncharacterized secreted proteins are preferentially expressed intracellular environment host macrophage. Furthermore, transcription these within cells was...
Invasive Salmonella typhimurium induces dramatic cytoskeletal changes on the membrane surface of mammalian epithelial cells and RAW264.7 macrophages as part its entry mechanism. Noninvasive S. strains are unable to induce this ruffling. invade in 2 h with 7- 10-fold higher levels than noninvasive strains. typhi, independent their ability replicate intracellularly, cytotoxic and, a greater degree, murine bone marrow-derived macrophages. Here, we show that macrophage cytotoxicity mediated by...
Intracellular pathogens and endogenous danger signals in the cytosol engage NOD-like receptors (NLRs), which assemble inflammasome complexes to activate caspase-1 promote release of proinflammatory cytokines IL-1β IL-18. However, NLRs that respond microbial vivo are poorly defined. We show NLRP3 NLRC4 both response Salmonella typhimurium. Responding distinct bacterial triggers, recruited ASC into a single cytoplasmic focus, served as site pro–IL-1β processing. Consistent with an important...
Macrophages respond to cytosolic nucleic acids by activating cysteine protease caspase-1 within a complex called the inflammasome. Subsequent cleavage and secretion of proinflammatory cytokines IL-1β IL-18 are critical for innate immunity. Here, we show that macrophages from mice lacking absent in melanoma 2 (AIM2) cannot sense double-stranded DNA fail trigger inflammasome assembly. Caspase-1 activation response intracellular pathogen Francisella tularensis also required AIM2....
Pathogenic Yersinia spp. carry a large common plasmid that encodes number of essential virulence determinants. Included in these factors are the -secreted proteins called Yops. We analyzed consequences wild-type and mutant strains pseudotuberculosis interactions with macrophage cell line RAW264.7 murine bone marrow-derived macrophages. Wild-type Y. kills ≈70% infected macrophages after an 8-h infection. show death mediated by is apoptosis. Mutant do not make any Yop no longer cause host...
Francisella tularensis is a highly infectious gram-negative coccobacillus that causes the zoonosis tularemia. This bacterial pathogen plague-like disease in humans after exposure to as few 10 cells. Many of mechanisms by which innate immune system fights are unknown. Here we show wild-type Francisella, reach cytosol, but not mutants remain localized vacuole, induced host defense response macrophages, dependent on caspase-1 and death-fold containing adaptor protein ASC. Caspase-1 ASC...
Human enteroids—epithelial spheroids derived from primary gastrointestinal tissue—are a promising model to study pathogen-epithelial interactions. However, accessing the apical enteroid surface is challenging because it enclosed within spheroid. We developed technique reverse polarity such that everts face media. Apical-out enteroids maintain proper and barrier function, differentiate into major intestinal epithelial cell (IEC) types, exhibit polarized absorption of nutrients. used this...
Host-adapted strains of Salmonella are capable establishing a persistent infection in their host often the absence clinical disease. The mouse model has primarily been used as for acute systemic Therefore, sites long-term S. typhimurium persistence not known nor mechanisms clearly understood. Here, we show that can persist long 1 yr mesenteric lymph nodes (MLNs) 129sv Nramp1+/+ (Slc11a1+/+) mice despite presence high levels anti–S. antibody. Tissues from colonized 60 d contain numerous...
A microarray-based negative selection screen was performed to identify Salmonella enterica serovar Typhimurium (serovar Typhimurium) genes that contribute long-term systemic infection in 129X1/SvJ (Nramp1r) mice. high-complexity transposon-mutagenized library used infect mice intraperitoneally, and the selective disappearance of mutants monitored after 7, 14, 21, 28 d postinfection. One hundred eighteen were identified spleens by The negatively selected represent many known aspects...
Francisella tularensis is a pathogenic bacterium whose virulence linked to its ability replicate within the host cell cytosol. Entry into macrophage cytosol activates host-protective multimolecular complex called inflammasome release proinflammatory cytokines interleukin (IL)-1β and -18 trigger caspase-1–dependent death. In this study, we show that cytosolic F. subspecies novicida (F. novicida) induces type I interferon (IFN) response essential for caspase-1 activation, inflammasome-mediated...
Francisella tularensis subverts the immune system to rapidly grow within mammalian hosts, often causing tularemia, a fatal disease. This pathogen targets cytosol of macrophages where it replicates by using genes encoded in pathogenicity island. However, bacteria are recognized host's ASC/caspase-1 pathway, which is essential for host defense, and leads macrophage cell death proinflammatory cytokine production. We used microarray-based negative selection screen identify that contribute growth...