A5064599385- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Influenza Virus Research Studies
- Fungal Infections and Studies
- Chemical Synthesis and Analysis
- Carbohydrate Chemistry and Synthesis
- Synthesis of β-Lactam Compounds
- Antifungal resistance and susceptibility
- Synthesis and Biological Evaluation
- Immune Response and Inflammation
- Galectins and Cancer Biology
- Inorganic and Organometallic Chemistry
- Synthesis and Catalytic Reactions
- Glycosylation and Glycoproteins Research
- Birth, Development, and Health
- Monoclonal and Polyclonal Antibodies Research
- Pregnancy and preeclampsia studies
- Vector-borne infectious diseases
- Respiratory viral infections research
- Various Chemistry Research Topics
- Political Systems and Governance
- Phagocytosis and Immune Regulation
University of Utah
2016-2025
Huntsman Cancer Institute
2013-2025
University of Newcastle Australia
2022
Wichita State University
2021
Icahn School of Medicine at Mount Sinai
2021
Bipar
2009-2019
University of South Dakota
2019
Washington University in St. Louis
2011-2017
Children’s Institute
2016
University of Cincinnati
2013
The design, synthesis, and in vitro evaluation of the novel carbocycles as transition-state-based inhibitors influenza neuraminidase (NA) are described. double bond position carbocyclic analogues plays an important role NA inhibition demonstrated by antiviral activity 8 (IC50 = 6.3 μM) vs 9 > 200 μM). Structure−activity studies a series 6a−i identified 3-pentyloxy moiety apparent optimal group at C3 with IC50 value 1 nM for inhibition. X-ray crystallographic structure 6h bound to revealed...
Many strategies have been proposed to induce tolerance transplanted tissue in rodents; however, few if any shown equal efficacy when tested nonhuman primate transplant models. We hypothesized that a critical distinction between specific pathogen-free mice and primates or human patients is their acquired immune history. Here, we show heterologous response — specifically, virally induced alloreactive memory potent barrier induction. A threshold of T cells needed promote rejection, CD8+...
Many strategies have been proposed to induce tolerance transplanted tissue in rodents; however, few if any shown equal efficacy when tested nonhuman primate transplant models. We hypothesized that a critical distinction between specific pathogen-free mice and primates or human patients is their acquired immune history. Here, we show heterologous response — specifically, virally induced alloreactive memory potent barrier induction. A threshold of T cells needed promote rejection, CD8+...
A series of influenza neuraminidase inhibitors with the cyclohexene scaffold containing lipophilic side chains have been synthesized and evaluated for B inhibitory activity. The size geometry modified systematically in order to investigate structure−activity relationships this class compounds. X-ray crystal structures several analogues complexed revealed that bound hydrophobic pocket consisted Glu276, Ala246, Arg224, Ile222 enzyme active site. relationship studies also demonstrated...
ABSTRACT We have recently described GS 4071, a carbocyclic transition-state analog inhibitor of the influenza virus neuraminidase, which has potent inhibitory activity comparable to that 4-guanidino-Neu5Ac2en (GG167; zanamivir) when tested against A replication and neuraminidase in vitro. now report 4071 is active several strains B viruses vitro oral 4104, an ethyl ester prodrug converted vivo, mouse ferret models infection. Oral administration 10 mg 4104 per kg body weight day caused...
Strong TCR signals favor the differentiation of short-lived effector T H 1 cells over long-lived memory cells.
IL-2 provides a memory differentiation signal to CD8+ T cells during the primary response that impacts ability of subsequent pool mount successful recall response. In this study, we find although effector CTL development is modestly decreased in absence IL-2, persistence short-term and long-term on pathogen clearance greatly diminished. Furthermore, secondary challenge lacking high-avidity IL-2R results failure repopulate pool. The role promoting not shared with highly related cytokine,...
Abstract Mixed hemopoietic chimerism has the potential to correct genetic hemological diseases (sickle cell anemia, thalassemia) and eliminate chronic immunosuppressive therapy following organ transplantation. To date, most strategies require either recipient conditioning (γ-irradiation, depletion of peripheral immune system) or administration “mega” doses bone marrow facilitate reliable engraftment. Although encouraging, many issues remain that may restrict prevent clinical application such...
Abstract Following a primary immune response, portion of effector T cells gives rise to long-lived memory cells. Although expansion and differentiation CD8 is dictated by brief exposure Ag, it unclear whether full also programmed within the same short window. By carefully modulating kinetics Listeria monocytogenes infection, we analyzed requirements for programming cell development in vivo. We find that although limiting infectious period first 24–48 h does not impact size ensuing population...
ABSTRACT An oral prodrug of GS 4071, a potent and selective inhibitor influenza neuraminidases, is currently under clinical development for the treatment prophylaxis virus infections in humans. To investigate potential resistance during use this compound, variants human A/Victoria/3/75 (H3N2) with reduced susceptibility to neuraminidase 4071 were selected vitro by passaging MDCK cells presence inhibitor. After eight passages, containing two amino acid substitutions hemagglutinin (A28T HA1...
Simultaneous blockade of the CD40 and CD28 T cell costimulatory pathways effectively promotes skin allograft survival in C3H/HeJ mice, extending median times (MSTs) beyond 100 days. This strategy is markedly less effective C57BL/6 with MSTs ranging between 20 30 In this study, we investigate underlying genetic causes these distinct phenotypes. Using H-2 congenic show that basis for varied responses two strains independent locus precursor frequency. mice treated costimulation are able to...
Cryptococcus neoformans is an opportunistic fungal pathogen that causes serious human disease in immunocompromised populations. Its polysaccharide capsule a key virulence factor which regulated response to growth conditions, becoming enlarged the context of infection. We used microarray analysis cells stimulated form over range conditions identify transcriptional signature associated with enlargement. The contains 880 genes, enriched for genes encoding known regulators, and includes many...
Abstract Many “nonmetastatic” cancers have spawned undetectable metastases before diagnosis. Eventual outgrowth of these microscopic lesions causes metastatic relapse and death, yet the events that dictate when how micrometastases convert to overt are largely unknown. We report macrophage-stimulating protein its receptor, Ron, key mediators in conversion bona fide through immune suppression. Genetic deletion Ron tyrosine kinase activity specifically host profoundly blocked metastasis. Our...
// Abhijit Ray 1,* , Matthew A. Williams 2,* Stephanie M. Meek 2 Randy C. Bowen 3 Kenneth F. Grossmann 1 Robert H.I. Andtbacka 4 Tawnya L. Bowles 5 John R. Hyngstrom 4,5 Sancy Leachman 6 Douglas Grossman Glen Sheri Holmen W. VanBrocklin Gita Suneja 7 and Hung T. Khong Division of Oncology, Huntsman Cancer Institute-University Utah, Salt Lake City, UT, USA Department Pathology, University School Medicine, Section Surgical General Surgery Surgery, Intermountain Medical Center, Murray,...
Tracking how individual naive T cells from a natural TCR repertoire clonally expand, differentiate, and make lineage choices in response to an infection has not previously been possible. Here, using single-cell sequencing technology identify clones by their unique sequences, we were able trace the clonal expansion, differentiation trajectory, commitment of virus-specific CD4 during acute lymphocytic choriomeningitis virus (LCMV) infection. Notably, found unappreciated diversity cellular...