A5066147484- Gamma-ray bursts and supernovae
- Stellar, planetary, and galactic studies
- Immune Response and Inflammation
- Tuberculosis Research and Epidemiology
- Immune cells in cancer
- Astronomy and Astrophysical Research
- interferon and immune responses
- Immune responses and vaccinations
- Mycobacterium research and diagnosis
- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- Astrophysical Phenomena and Observations
- Galaxies: Formation, Evolution, Phenomena
- CCD and CMOS Imaging Sensors
- Cosmology and Gravitation Theories
- Cytokine Signaling Pathways and Interactions
- Astrophysics and Cosmic Phenomena
- Single-cell and spatial transcriptomics
- Cholesterol and Lipid Metabolism
- Infrared Target Detection Methodologies
- Adaptive optics and wavefront sensing
- Pediatric health and respiratory diseases
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Astro and Planetary Science
Infectious Disease Research Institute
2017-2025
University of Washington
1995-2021
Center for Infectious Disease Research
2011-2017
Institute for Systems Biology
2004-2011
California Institute of Technology
2000-2001
We present spectral and photometric observations of 10 Type Ia supernovae (SNe Ia) in the redshift range 0.16 ≤ z 0.62. The luminosity distances these objects are determined by methods that employ relations between SN light curve shape. Combined with previous data from our High-z Supernova Search Team recent results Riess et al., this expanded set 16 high-redshift a 34 nearby used to place constraints on following cosmological parameters: Hubble constant (H0), mass density (ΩM), (i.e.,...
The High-Z Supernova Search is an international collaboration to discover and monitor Type Ia supernovae (SNe Ia) at z > 0.2 with the aim of measuring cosmic deceleration global curvature. Our has pursued a basic understanding in nearby universe, discovering observing large sample objects developing methods measure accurate distances SNe Ia. This paper describes extension this program ≥ 0.2, outlining our search techniques follow-up program. We have devised high-throughput filters that...
We use Type Ia supernovae studied by the High-z Supernova Search Team to constrain properties of an energy component that may have contributed accelerating cosmic expansion. find for a flat geometry equation-of-state parameter unknown component, αx = Px/ρx, must be less than -0.55 (95% confidence) any value Ωm, and it is further limited < -0.60 if Ωm assumed greater 0.1. These values are inconsistent with being topological defects such as domain walls, strings, or textures. The supernova...
We have coordinated Hubble Space Telescope (HST) photometry with ground-based discovery for three supernovae: Type Ia supernovae near z ≈ 0.5 (SN 1997ce, SN 1997cj) and a third event at = 0.97 1997ck). The superb spatial resolution of HST separates each supernova from its host galaxy leads to good precision in the light curves. use these curves relations between luminosity, light-curve shape, color calibrated low-z samples derive relative luminosity distances that are accurate 10% 20% 1....
Significance The lipid 25-hydroxycholesterol (25HC) is produced by immune cells in response to infection. We demonstrate that addition interfering with viral entry and replication, 25HC also amplifies the activation of increases production mediators. Furthermore, we show presence actually harmful setting infection influenza because these mediators leads damage host. These observations might have particular relevance for understanding mechanisms behind high pathogenicity several recently...
Alveolar macrophages (AMs) play a critical role during Mycobacterium tuberculosis (Mtb) infection as the first cells in lung to encounter bacteria. We previously showed that AMs initially respond Mtb vivo by mounting cell-protective, rather than pro-inflammatory response. However, plasticity of initial AM response was unknown. Here, we characterize how previous exposure , either through subcutaneous vaccination with bovis (scBCG) or contained (coMtb) mimics aspects concomitant immunity,...
We present observations of the Type Ia supernovae (SNe) 1999M, 1999N, 1999Q, 1999S, and 1999U, at redshift z ≈ 0.5. They were discovered in early 1999 with 4.0 m Blanco telescope Cerro Tololo Inter-American Observatory by High-z Supernova Search Team (HZT) subsequently followed many ground-based telescopes. SNe 1999Q 1999U also observed Hubble Space Telescope. computed luminosity distances to new using two methods added them high-z diagram that HZT has been constructing since 1995. The...
Induction of an NRF2-dependent cell-protective signature impairs alveolar macrophages from controlling M.tb. infection in vivo.
Cancer cells are heterogeneous and, it has been proposed, fall into at least two classes: the tumor-initiating cancer stem (CSC) and more differentiated tumor cells. The transmembrane protein CD133 widely used to isolate putative CSC populations in several types, but its validity as a marker hence clinical ramifications remain controversial. Here, we conducted transcriptomic profiling of sorted + − from human glioblastoma multiforme (GBM) by subtractive analysis, established gene expression...
We have measured the rest-frame B,V, and I-band light curves of a high-redshift type Ia supernova (SN Ia), SN 1999Q (z=0.46), using HST ground-based near-infrared detectors. A goal this study is measurement color excess, E_{B-I}, which sensitive indicator interstellar or intergalactic dust could affect recent cosmological measurements from SNe Ia. Our observations disfavor 30% opacity visual by as an alternative to accelerating Universe. This statement applies both Galactic-type (rejected at...
GRB 970828 was the first well-localized γ-ray burst (GRB) X-ray afterglow for which no optical found despite a prompt, deep search down to Rlim ~ 24.5 mag. We report discovery of short-lived radio flare within localization error circle this burst. Such flares are seen in about 25% afterglows, and their origin is not well understood. The precise position enabled us identify likely host galaxy measure its redshift, z = 0.9578. appears be an interacting/merging system. Under assumption that...
Antiviral responses must rapidly defend against infection while minimizing inflammatory damage, but the mechanisms that regulate magnitude of response within an infected cell are not well understood. miRNAs small non-coding RNAs suppress protein levels by binding target sequences on their cognate mRNA. Here, we identify miR-144 as a negative regulator host antiviral response. Ectopic expression resulted in increased replication three RNA viruses primary mouse lung epithelial cells: influenza...
Progress in tuberculosis vaccine development is hampered by an incomplete understanding of the immune mechanisms that protect against infection with Mycobacterium (Mtb), causative agent tuberculosis. Although M72/ASOE1 trial yielded encouraging results (54% efficacy subjects prior exposure to Mtb), a highly effective adult remains elusive. We show mouse model, establishment contained and persistent yet non-pathogenic Mtb ("contained infection", CMTB) rapidly durably reduces disease burden...
Mycobacterium tuberculosis (MTB) is a major global cause of mortality worldwide, responsible for over million deaths annually. Despite this burden, natural immunity prevents disease in more than 90% exposed individuals. Previous studies have identified interferon-gamma (IFN-γ) as key regulator innate immune defense against MTB. Here, we investigate the impact IFN-γ timing on macrophage-mediated control MTB infection. We demonstrate that exposure before infection enhances macrophage...
Alveolar macrophages (AMs) are lung-resident myeloid cells and airway sentinels for inhaled pathogens environmental particles. While AMs can be highly inflammatory in response to respiratory viruses, they do not mount proinflammatory responses all airborne pathogens. For example, we previously showed that fail a robust Mycobacterium tuberculosis. Here, address this discrepancy by investigating the capacity of murine direct innate immune sensing, using LPS as model. Use LPS-coated fluorescent...
GRB 000926 has one of the best-studied afterglows to date, with multiple X-ray observations, as well extensive multifrequency optical and radio coverage. Broadband afterglow spanning from frequencies, provide a probe density structure circumburst medium, ejecta energetics, geometry, physical parameters relativistic blast wave resulting explosion. We present an analysis Chandra X-Ray Observatory observations this event, along Hubble Space Telescope monitoring data. combine these data...
Precise control of the innate immune response is essential to ensure host defense against infection while avoiding inflammatory disease. Systems-level analyses Toll-like receptor (TLR)-stimulated macrophages suggested that SHANK-associated RH domain-interacting protein (SHARPIN) might play a role in TLR pathway. This hypothesis was supported by observation derived from chronic proliferative dermatitis mutation ( cpdm ) mice, which harbor spontaneous null Sharpin gene, exhibited impaired...
Summary Pulmonary Mycobacterium tuberculosis (Mtb) infection results in highly heterogeneous lesions ranging from granulomas with central necrosis to those primarily comprised of alveolitis. While alveolitis has been associated prior immunity human post-mortem studies, the drivers these distinct pathologic outcomes are poorly understood. Here, we show that divergent lesion structures can be modeled C3HeB/FeJ mice and regulated by immunity. Using quantitative imaging, scRNAseq, flow...
The optical light curve of the energetic γ-ray burst GRB 991216 is consistent with jetlike behavior in which a power-law decay steepens from t-1.22±0.04 at early times to t-1.53±0.05 gradual transition around 2 days. derivation late-time slope takes into account constant contribution host or intervening galaxy, was measured 110 days after event R = 24.56 ± 0.14, although deviates single power law whether not term included. early-time spectral energy distribution afterglow can be described as...
The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and to investigate host-pathogen interactions at a systems level. This generated 47 transcriptomic proteomic datasets from 30 studies that in vivo vitro host responses viral infections. Human pathogens Orthomyxoviridae Coronaviridae families, especially pandemic H1N1 avian H5N1 influenza A viruses severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated....
Type I alveolar epithelial cells are a replicative niche for influenza in vivo, yet their response to infection is not fully understood. To better characterize cellular responses, we have created an immortalized murine lung type cell line (LET1). These support spreading virus the absence of exogenous protease and thus permit simultaneous analysis viral replication dynamics host responses. LET1 can be productively infected with human, swine mouse-adapted strains exhibit expression antiviral...
We report on optical, near-infrared and centimeter radio observations of GRB000418 which allow us to follow the evolution afterglow from 2 200 days after gamma-ray burst. In modeling these broad-band data, we find that an isotropic explosion in a constant density medium is unable simultaneously fit both optical data. However, jet-like outflow with opening angle 10-20 degress provides good description The evidence favor jet interpretation based behavior light curves, since expected break...
Influenza viruses exhibit large, strain-dependent differences in pathogenicity mammalian hosts. Although the characteristics of severe disease, including uncontrolled viral replication, infection lower airway, and highly inflammatory cytokine responses have been extensively documented, specific virulence mechanisms that distinguish pathogenic strains remain elusive. In this study, we focused on early events influenza infection, measuring growth rate three varying mouse airway epithelium...
We present multicolor light curves of the optical afterglow gamma-ray burst (GRB) 000926. Beginning ~1.5 days after burst, this GRB steepen measurably. The existence such achromatic breaks is usually taken to be an important observational signature that ejecta are not expanding isotropically but rather have a collimated jetlike geometry. If we interpret data in context, derive opening angle 5°, which reduces energy release compared with isotropic model by factor ~275, 1.7 × 1051 ergs. To fit...