A5052017649- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- Blood properties and coagulation
- Immunodeficiency and Autoimmune Disorders
- Cancer Immunotherapy and Biomarkers
- Hemoglobinopathies and Related Disorders
- Glycosylation and Glycoproteins Research
- Iron Metabolism and Disorders
- RNA modifications and cancer
- CAR-T cell therapy research
- Prenatal Screening and Diagnostics
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- RNA Research and Splicing
- Systemic Lupus Erythematosus Research
- Dermatology and Skin Diseases
- Erythrocyte Function and Pathophysiology
- Protein Interaction Studies and Fluorescence Analysis
- Plant pathogens and resistance mechanisms
- Cytokine Signaling Pathways and Interactions
- Psoriasis: Treatment and Pathogenesis
- Exercise and Physiological Responses
- Cancer Genomics and Diagnostics
- Protein purification and stability
Alpine Immune Sciences (United States)
2018-2023
Bristol-Myers Squibb (United States)
2016
Bristol-Myers Squibb (Germany)
2012-2015
Protein Research Foundation
2009
HistoGenetics (United States)
2000
Dow Chemical (United States)
1993
Fred Hutch Cancer Center
1988-1990
University of Washington
1981-1988
Cancer Research Center
1988
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
1988
The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity share many biological properties. Both been implicated as factors contributing to the progression inflammatory autoimmune diseases. Moreover, reagents that neutralize significantly ameliorate disease severity in several mouse models human disease. mediates its effects through interaction with cognate receptor, IL-17 receptor (IL-17RA). We report here IL-17RA-related molecule, IL-17RC is for IL-17F....
Members of the CD28 family play important roles in regulating T-cell functions and share a common gene structure profile. We have identified VSTM3 as protein whose matches that other members. This (also known TIGIT WUCAM) has been previously shown to affect immune responses is expressed on NK cells, activated memory T Tregs. The nectin-family proteins CD155 CD112 serve counter-structures for VSTM3, also bind activating receptor CD226 cells cells. Hence, this group interacting forms network...
Significance Fc gamma receptor I (FcγRI) contributes to protective immunity against bacterial infections, but exacerbates certain autoimmune diseases. It is the sole high-affinity for IgG and plays a significant role in immunotherapy. To date, there no structural information available on how recognizes its antibody ligands, however. Consequently, mechanism of binding remains unclear. We report first structure complex with IgG-Fc. The work reveals direct recognition glycan as major factor...
Objective Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and nephritis. We undertook this study to develop evaluate a high‐affinity antagonist overcome clinical limitations existing B cell inhibitors. Methods A variant TACI‐Fc generated by directed evolution showed enhanced binding for both APRIL BAFF was designated povetacicept (ALPN‐303). Povetacicept compared wild‐type (WT) related molecules vitro...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharacterization of complementary deoxyribonucleic acid and genomic for the .beta. chain human fibrinogenDominic W. Chung, Benito G. Que, Mark Rixon, Myles Mace, Jr., Earl DavieCite this: Biochemistry 1983, 22, 13, 3244–3250Publication Date (Print):June 21, 1983Publication History Published online1 May 2002Published inissue 21 June 1983https://pubs.acs.org/doi/10.1021/bi00282a032https://doi.org/10.1021/bi00282a032research-articleACS...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharacterization of a complementary deoxyribonucleic acid coding for the .alpha. chain human fibrinogenMark W. Rixon, Wai Yee Chan, Earl Davie, and Dominic ChungCite this: Biochemistry 1983, 22, 13, 3237–3244Publication Date (Print):June 21, 1983Publication History Published online1 May 2002Published inissue 21 June 1983https://pubs.acs.org/doi/10.1021/bi00282a031https://doi.org/10.1021/bi00282a031research-articleACS PublicationsRequest reuse...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleotide sequence of the gene for .gamma. chain human fibrinogenMark W. Rixon, Dominic Chung, and Earl DavieCite this: Biochemistry 1985, 24, 8, 2077–2086Publication Date (Print):April 9, 1985Publication History Published online1 May 2002Published inissue 9 April 1985https://pubs.acs.org/doi/10.1021/bi00329a041https://doi.org/10.1021/bi00329a041research-articleACS PublicationsRequest reuse permissionsArticle Views83Altmetric-Citations36LEARN...
Abstract Background Overexpression or administration of interleukin 31 ( IL ‐31) has been shown to induce a profound itch response in mice and dogs. The chronic pruritus observed mouse ‐31 transgenic results the development skin lesions alopecia through excoriation from excessive scratching, condition similar that patients with atopic dermatitis AD ). Objective To test whether induces non‐human primates and, if so, treatment an anti‐ neutralizing monoclonal antibody mA b) can block response....
Despite the recent clinical success of T cell checkpoint inhibition targeting CTLA-4 and PD-1 pathways, many patients either fail to achieve objective responses or they develop resistance therapy. In some cases, poor blockade have been linked suboptimal CD28 costimulation inability generate maintain a productive adaptive anti-tumor immune response. To address this, here we utilize directed evolution engineer CD80 IgV domain with increased PD-L1 affinity fuse this an immunoglobulin Fc domain,...
Recombinant plasmids containing bovine cDNA have been screened with a radiolabeled enriched for fibrinogen. A number of cDNAs fibrinogen were identified by this assay. One plasmid, designated pBI beta 1, was found to contain insert 1372 base pairs. The sequence the plasmid then determined. It shown code 424 amino acids chain fibrinogen, starting residue 44. This and other data made it possible construct complete acid protein. Comparison corresponding human molecule indicated that two chains...
Single base substitutions have been identified in the promoter regions of A gamma-globin genes from individuals with certain types nondeletion gamma hereditary persistence fetal hemoglobin (HPFH). The presence these mutations is closely associated HPFH phenotype, but proof that they are determinants lacking. To test directly whether can result an increase gene transcription, we studied cosmid clones containing G gamma- through beta-globin Greek-type (G-to-A substitution at -117) and...
Binding of immune complexes to cellular FcgammaRs can promote cell activation and inflammation. In previous studies, a recombinant human (rh) soluble FcgammaR, rh-FcgammaRIA (CD64A), was shown block inflammation in passive transfer models complex-mediated disease. To assess whether could T cell- B cell-dependent model disease, the efficacy collagen-induced arthritis evaluated. Mice with established were treated single s.c. injection (0.2-2.0 mg/dose) given every other day for 11 days....
CD28 and inducible T cell costimulator (ICOS) appear to have nonredundant roles in activation adaptive immunity. We undertook this study characterize vitro vivo the therapeutic potential of acazicolcept (ALPN-101), an Fc fusion protein a human variant ICOS ligand (ICOSL) domain designed inhibit both costimulation, inflammatory arthritis.Acazicolcept was compared with inhibitors either or pathways (abatacept belatacept [CTLA-4Ig], prezalumab [anti-ICOSL monoclonal antibody]) receptor binding...
Cross-species hybridizations have enabled us to isolate and clone the gene for beta chain of human fibrinogen. Highlights revealed by nucleotide sequence analyses, particularly in areas that a direct bearing on defining overall organization gene, been presented. Nucleotide determination has confirmed presence seven intervening sequences. The positions where several these sequences interrupt coding region appear be related functional domains polypeptide. A putative signal peptide identified....
Increased levels of serum IgE are associated with greater asthma prevalence and disease severity. depletion using an anti-IgE monoclonal antibody has met success in the treatment moderate-to-severe severe persistent allergic asthma.To test whether B cell-targeted therapy is a more effective for airway hyperresponsiveness (AHR) murine model compared IgE-depletion.We delivered soluble mTACI-Ig, receptor cell survival factors BLyS (B Lymphocyte Stimulator) APRIL (A PRoliferation-Inducing...
Interleukin-21 (IL-21) is a type I four-helical bundle cytokine that exerts variety of significant effects on many hematopoietic cells, including T and B lymphocytes natural killer cells. IL-21 produced predominantly by CD4+ cells and, when aberrantly overexpressed, appears to play important roles in wide autoimmune disorders. To generate potential therapeutic reagents capable inhibiting for clinical use, we immunized human immunoglobulin transgenic mice with then identified cloned panel...
Immunoglobulin superfamily member (IgSF) proteins play a significant role in regulating immune responses with surface expression on all cell subsets, making the IgSF an attractive family of for therapeutic targeting human diseases. We have developed directed evolution platform capable engineering domains to increase affinities cognate ligands and/or introduce binding non-cognate ligands. Using this scientific platform, ICOSL been derived enhanced ICOS and additional high-affinity receptor,...
Abstract The DNA sequence of the mouse H chain V regions from five hybridomas directed against human tumor Ag tumor-associated glycoprotein-72 (TAG-72) have been determined. This includes a previously determined VH gene first-generation anti-TAG-72 mAb, B72.3, and sequences four second-generation CC49, CC83, CC46, CC92. A comparison revealed high degree shared identity between productively rearranged genes, suggesting derivation common germ line region gene. In process cloning unrearranged...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExpression of the human .gamma.-globin gene after retroviral transfer to transformed erythroid cellsMark W. Rixon, Edith A. S. Harris, and Richard E. GelinasCite this: Biochemistry 1990, 29, 18, 4393–4400Publication Date (Print):May 8, 1990Publication History Published online1 May 2002Published inissue 8 1990https://doi.org/10.1021/bi00470a019RIGHTS & PERMISSIONSArticle Views36Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are...
A recombinant soluble version of the human high-affinity receptor for IgG, rh-FcγRIA or CD64A, was expressed in mammalian cells and purified from their conditioned media. As assessed by circular dichroism, size exclusion chromatography dynamic light scattering, incubation at 37°C resulted time-dependent formation aggregates caused protein unfolding loss native structure. Aggregate irreversible, temperature-dependent independent concentration. Aggregated lost its ability to inhibit immune...
Single base substitutions have been identified in the promoter regions of A gamma-globin genes from individuals with certain types nondeletion gamma hereditary persistence fetal hemoglobin (HPFH). The presence these mutations is closely associated HPFH phenotype, but proof that they are determinants lacking. To test directly whether can result an increase gene transcription, we studied cosmid clones containing G gamma- through beta-globin Greek-type (G-to-A substitution at -117) and...