A5108028531- Hepatitis C virus research
- Hepatitis B Virus Studies
- Synthetic Organic Chemistry Methods
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Psoriasis: Treatment and Pathogenesis
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Cancer Treatment and Pharmacology
- Liver Disease Diagnosis and Treatment
- Marine Sponges and Natural Products
- HIV Research and Treatment
- Immunodeficiency and Autoimmune Disorders
- Oxidative Organic Chemistry Reactions
- Immune Response and Inflammation
- Hepatitis Viruses Studies and Epidemiology
- SARS-CoV-2 detection and testing
- Renal Transplantation Outcomes and Treatments
- IL-33, ST2, and ILC Pathways
- Microbial Natural Products and Biosynthesis
- Inflammatory Bowel Disease
- Biosensors and Analytical Detection
- Asymmetric Synthesis and Catalysis
- Autoimmune Bullous Skin Diseases
Eli Lilly (United States)
2019-2020
Stanford University
2017-2020
Columbia University
2011-2015
Curtin University
2014
Cornell University
2012
Harvard University
2009
Queen Mary Hospital
1996-2008
University of Hong Kong
1996-2008
Palo Alto Research Center
2004
Cellular Research (United States)
2001
Interferons (IFNs) are the most important cytokines in antiviral immune responses. “Natural IFN-producing cells” (IPCs) human blood express CD4 and major histocompatibility complex class II proteins, but have not been isolated further characterized because of their rarity, rapid apoptosis, lack lineage markers. Purified IPCs here shown to be + CD11c − type 2 dendritic cell precursors (pDC2s), which produce 200 1000 times more IFN than other cells after microbial challenge. pDC2s thus an...
Toll-like receptors (TLRs) are ancient microbial pattern recognition highly conserved from Drosophila to humans. To investigate if subsets of human dendritic cell precursors (pre-DC), including monocytes (pre-DC1), plasmacytoid DC (pre-DC2), and CD11c+ immature DCs (imDCs) developed recognize different microbes or antigens, we studied their TLR expression responses antigens. We demonstrate that whereas preferentially express 1, 2, 4, 5, 8, pre-DC strongly 7 9. In accordance with these...
We describe a fully data driven model that learns to perform retrosynthetic reaction prediction task, which is treated as sequence-to-sequence mapping problem. The end-to-end trained has an encoder–decoder architecture consists of two recurrent neural networks, previously shown great success in solving other tasks such machine translation. on 50,000 experimental examples from the United States patent literature, span 10 broad types are commonly used by medicinal chemists. find our performs...
The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% the euchromatic DNA. A single contig 26 megabases (Mb) spans entire short arm, five contigs separated by gaps totalling 320 kb span long arm this metacentric chromosome. An additional 234,339 bp has been determined within pericentromeric region arm. We annotated 727 genes 168 pseudogenes in sequence. About 64% these have a 5' 3' untranslated complete open reading frame. Comparative analysis...
Upon viral stimulation, the natural interferon (IFN)-α/β–producing cells (IPCs; also known as pre-dendritic (DCs 2) in human blood and peripheral lymphoid tissues rapidly produce huge amounts of IFN-α/β. After performing this innate antiviral immune response, IPCs can differentiate into DCs strongly stimulate T cell–mediated adaptive responses. Using four-color immunofluorescence flow cytometry, we have mapped developmental pathway pre-DC2/IPCs from CD34+ hematopoietic stem fetal liver, bone...
A gram-scale route to bryostatin Scientists once accumulated 14 tons of the red, bushy, tufted sea creature Bugula neritina extract 18 grams 1. The macrocyclic organic compound is under study for treatment HIV, cancer, and Alzheimer's disease but has proven frustratingly scarce. Wender et al. report a 29-step chemical synthesis 1 that proceeds in 4.8% overall yield provides gram quantities (see Perspective by Lanman). Intermediates along pathway can be straightforwardly modified produce...
Dysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role interleukin (IL)-23-producing mononuclear phagocytes disease pathogenesis. Mechanistic insights into regulation IL-23 prerequisite for selective targeting therapies as part personalised medicine.We performed transcriptomic analysis to investigate expression human peripheral blood cells. We investigated used single-cell RNA sequencing derive signature hyperinflammatory monocytes. Using gene...
Natural killer T (NKT) cells are a highly conserved subset of that have been shown to play critical role in suppressing helper cell type 1–mediated autoimmune diseases and graft versus host disease an interleukin (IL)-4–dependent manner. Thus, it is important understand how the development IL-4– interferon (IFN)-γ–producing NKT regulated. Here, we show from adult blood those cord undergo massive expansion numbers (500–70,000-fold) during 4-wk culture with IL-2, IL-7, phytohemagglutinin,...
Hepatitis B surface antigen (HBsAg)-positive kidney transplant recipients have increased liver-related mortality. The impact of lamivudine treatment on patient survival, the optimal time to start treatment, and feasibility discontinuing not been determined. This study examined these issues with a novel management protocol. Serum hepatitis virus (HBV) DNA levels were measured serially in HBsAg-positive recipients, was administered preemptively patients increasing HBV or without elevation...
The enantioselective crotylation of aldehydes with 1,2-diaminochlorocrotylsilane reagents is effectively catalyzed by Sc(OTf)(3). one significant limitation on the utility these reagents--substrate scope--has thus been addressed. net result most comprehensive and highly practical method for aldehyde yet advanced.
A highly efficient and step-economical synthesis of zincophorin methyl ester has been achieved. The unprecedented step economy this is principally due to an application the tandem silylformylation-crotylsilylation/Tamao oxidation-diastereoselective tautomerization reaction, which achieves in a single what would typically require significant multistep sequence.
Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin neither evolved nor optimized human disease. Here we report design, synthesis, biological evaluation several close-in analogs 1. Using function-oriented synthesis approach, synthesize series designed to maintain affinity bryostatin's target protein kinase C (PKC) while enabling...
A convergent synthesis of the marine natural product (+)-peloruside has been reported. This target assembled through successive application two methyl ketone boron aldol addition reactions to latent C7−C11 dialdehyde synthon. approach afforded a 22-step this product. The influence resident stereocenters on reaction diastereoselection examined in detail.
HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate expression latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs PKC modulator LRA bryostatin (termed...
Less is more: An efficient synthesis of the anti-mitotic macrolide dictyostatin proceeds with a longest linear sequence 14 steps, and allows rapid production multi-gram quantities each three fragments from which natural product assembled in just four or five steps. The key step scalable one-step C(12)–C(14) C(20)–C(22) stereotriads.
Laboratory-based RT-PCR, the current gold standard for COVID-19 testing, can require a turnaround time of 24 to 48 h from sample collection result. The delayed result limits effectiveness centralized RT-PCR testing reduce transmission and stem potential outbreaks.
A highly sensitive and rapid assay has been developed to quantify hepatitis B virus (HBV) DNA, based on the fluorescence resonance energy transfer principle real-time PCR, using LightCycler a pair of specific fluorescent hybridization probes. This PCR (LC-PCR) detected HBV DNA in linear range from 10(1) 10(8) copies per reaction (250-2.5 x 10(9) ml(-1)), with cycling time 35 min. The was validated two EUROHEP standards (ad ay subtypes) exhibited low intra-assay (< 6 %) inter-assay 16...
SUMMARY: Aim: Pegylated interferon (PEG‐IFN) combined with ribavirin is recommended for the treatment of chronic hepatitis C virus (HCV) infection in patients without renal failure. The optimal dialysis remains to be established. A high incidence adverse effects has been observed conventional and PEG‐IFN alpha‐2b patients. Methods: We conducted a prospective study investigate tolerability efficacy alpha‐2a (135 µg weekly 48 weeks) six HCV infection. Results: Two completed weeks treatment....
ABSTRACT A rapid cytomegalovirus (CMV) pp65 antigenemia assay with direct erythrocyte lysis (DL) 0.8% NH 4 Cl, followed by indirect immunofluorescence staining (IF), was evaluated 82 blood samples from renal transplant recipients, and the results were compared to those of conventional dextran sedimentation two-cycle alkaline phosphatase, anti-alkaline phosphatase (DS-APAAP). The DL-IF modification gave a higher leukocyte yield DS-APAAP (75.4 versus 54.9%; P < 0.05), similar viability...
ABSTRACT The optimal hepatitis B virus (HBV) DNA quantitative assay for clinical use remains to be determined. We examined the sensitivity, linearity, and variability of a novel second-generation antibody capture solution hybridization assay, Digene Hybrid Capture II (HCII), compared it with another widely used branched-DNA (bDNA) (Quantiplex; Chiron Corp.). Our results showed similar satisfactory linearity values, as well interassay intra-assay both HCII bDNA assays across different ranges...