A5085474573- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Protein purification and stability
- Inflammasome and immune disorders
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Viral Infectious Diseases and Gene Expression in Insects
- Glycosylation and Glycoproteins Research
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Biosimilars and Bioanalytical Methods
- Immunodeficiency and Autoimmune Disorders
- Genetic Mapping and Diversity in Plants and Animals
- Advanced biosensing and bioanalysis techniques
- Genetic and phenotypic traits in livestock
- Reproductive System and Pregnancy
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Toxin Mechanisms and Immunotoxins
- Cardiovascular Disease and Adiposity
- Burkholderia infections and melioidosis
- Cancer Immunotherapy and Biomarkers
- Metabolism, Diabetes, and Cancer
- IL-33, ST2, and ILC Pathways
Amgen (United States)
2017-2025
MSM Protein Technologies (United States)
2022
University of North Carolina at Chapel Hill
2012-2019
UNC Lineberger Comprehensive Cancer Center
2015
Indiana University School of Medicine
2013
University of Rochester
2009-2010
Genotyping microarrays are an important resource for genetic mapping, population genetics, and monitoring of the integrity laboratory stocks. We have developed third generation Mouse Universal Array (MUGA) series, GigaMUGA, a 143,259-probe Illumina Infinium II array house mouse (Mus musculus). The bulk content GigaMUGA is optimized mapping in Collaborative Cross Diversity Outbred populations, substrain-level identification mice. In addition to 141,090 single nucleotide polymorphism probes,...
Abstract NK cells have well-established functions in immune defense against virus infections and cancer through their cytolytic activity production of cytokines. In this study, we examined the frequency influence on T cell responses mice given variants lymphocytic choriomeningitis that cause acute or persisting infection. We found increased frequencies circulating during disseminating infection compared with uninfected acutely infected mice. Consistent recent reports, observed depletion...
A CD25-dependent IL-2 mutein expanded regulatory T cells and controlled spontaneous diabetes in nonobese diabetic (NOD) mice.
Therapeutic approaches are needed to promote T cell-mediated destruction of poorly immunogenic, "cold" tumors typically associated with minimal response immune checkpoint blockade (ICB) therapy. Bispecific cell engager (BiTE) molecules induce redirected lysis cancer cells by polyclonal and have demonstrated promising clinical activity against solid in some patients. However, little is understood about the key factors that govern responses these therapies. Using an immunocompetent mouse model...
Appropriate immune responses require a fine balance between activation and attenuation. NLRC3, non-inflammasome-forming member of the NLR innate receptor family, attenuates inflammation in myeloid cells proliferation epithelial cells. T lymphocytes express highest amounts Nlrc3 transcript where its physiologic relevance is unknown. We show that NLRC3 attenuated interferon-γ TNF expression by CD4+ reduced helper 1 (Th1) Th17 cell proliferation. Nlrc3−/− mice exhibited increased prolonged to...
The differentiation of CD4(+) T cells into the Th2 subset is controlled by transcription factor GATA-3. GATA-3 both necessary and sufficient for works through induction chromatin remodeling at effector cytokine loci. We show in this study that IL-4 stimulation induces mRNA upregulation, but level protein induced insufficient differentiation. levels are enhanced concomitant TCR signaling PI3K/mammalian target rapamycin pathway. PI3K-mediated increase occurs without increasing level. Rather,...
Abstract There is a need to understand better how improve B cell responses and immunity persisting virus infections, which often cause debilitating illness or death. People with chronic infection show evidence of improved control when there strong neutralizing antibody response, conversely, dysfunction associated higher viral loads. We showed previously that NK cells inhibit CD4+ CD8+ T disseminating LCMV depletion attenuates infection. Here, we examined the effect on in mice. Whereas mice...
Biologic drug discovery pipelines are designed to deliver protein therapeutics that have exquisite functional potency and selectivity while also manifesting biophysical characteristics suitable for manufacturing, storage, convenient administration patients. The ability use computational methods predict properties from sequence, potentially in combination with high throughput assays, could decrease timelines increase the success rates therapeutic developability engineering by eliminating...
Vascular smooth muscle cell (VSMC) and immune diversification play a central role in driving atherosclerotic coronary artery disease (CAD). However, the molecular mechanisms governing state transitions within neo-intima human CAD remain poorly understood, no lipid-independent therapies are currently approved for its treatment. Here, we performed multi-omic single-cell gene expression profiling, epitope mapping, spatial transcriptomics from 27 arteries. Our analysis identified fibroblast...
AMG 256 is a bi-specific, heteroimmunoglobulin molecule with an anti-PD-1 antibody domain and single IL-21 mutein on the C-terminus. Nonclinical studies in cynomolgus monkeys revealed that administration led to development of immunogenicity-mediated responses indicated could enhance anti-drug response directed toward monoclonal domain. Anti-AMG IgE were also observed monkeys. A first-in-human (FIH) study patients advanced solid tumors was designed these risks mind. elicited ADA 28 33...
Ongoing clinical trials are evaluating the benefits of systemic blockade lymphocyte activation gene-3 (LAG-3) signals to improve immunity tumors. Those studies founded on well-established inhibitory role LAG-3 in regulating CD8(+) T cells during chronic virus infection and antitumor responses. However, cell response LAG-3-deficient mice is similar size function that wild type animals, suggesting has nuanced immune-regulatory functions. We performed a series adoptive transfer experiments...
Abstract Oligonucleotide therapeutics use short interfering RNA (siRNA) or antisense oligonucleotide (ASO) molecules to exploit endogenous systems—neutralizing target prevent subsequent protein translation. While the potential clinical application is vast, delivery efficiency and extrahepatic targeting challenging. Bioanalytical assays are important in building understanding of these complex relationships. The literature currently lacks description robust sensitive methods measure siRNA ASOs...
In vivo clearance mechanisms of therapeutic monoclonal antibodies (mAbs) encompass both target-mediated and target-independent processes. Two distinct determinants overall mAb largely separate influences are non-specific cellular endocytosis subsequent pH-dependent recycling mediated by the neonatal Fc receptor (FcRn), where inter-mAb variability in efficiency processes is observed. Here, we implemented a functional cell-based FcRn assay via Madin-Darby canine kidney type II cells stably...
As the pharmaceutical industry places greater emphasis on pairing biological pathways with appropriate therapeutic intervention, an increase in use of biologic drugs has emerged. With increasing complexity biotherapeutics, absorption, distribution, metabolism, and excretion (ADME) studies have also become increasingly complex. The characterization ADME properties is critical to tuning pharmacokinetic profiles next generation biologics (NGBs). knowledge fate a drug essential for enhancement...
Abstract Past studies have demonstrated higher clearance for monoclonal antibodies possessing increased rates of non-specific endocytosis. However, this metric is oftentimes evaluated indirectly using biophysical techniques or cell surface binding that may not provide insight into the specific cellular turnover. Furthermore, few examples evaluating endocytosis been reported a therapeutic antibody reached clinical assessment. In current report, we human immunoglobulin G2 targeted against...
Arenaviruses can cause severe hemorrhagic disease in humans, which progress to organ failure and death. The underlying mechanisms causing lethality person-to-person variation outcome remain incompletely explained. Herein, we characterize a mouse model that recapitulates many features of pathogenesis observed humans with arenavirus-induced disease, including thrombocytopenia, vascular leakage, lung edema, lethality. susceptibility congenic B6.PL mice lymphocytic choriomeningitis virus (LCMV)...
Abstract Interleukin-2 (IL-2) controls the homeostasis and function of regulatory T cells (Tregs) defects in IL-2 pathway contribute to multiple autoimmune diseases. Although recombinant therapy has been efficacious certain inflammatory conditions, capacity for also activate effector responses highlights need IL-2-based therapeutics with improved Treg-specificity. From a panel rationally designed variants, we identified muteins reduced potency enhanced Treg-selectivity due increased...