A5078393068- Immune Cell Function and Interaction
- Advanced biosensing and bioanalysis techniques
- T-cell and B-cell Immunology
- Histone Deacetylase Inhibitors Research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Amino Acid Enzymes and Metabolism
- Immunotherapy and Immune Responses
- Diabetes Treatment and Management
- Biosensors and Analytical Detection
- Ubiquitin and proteasome pathways
- Congenital heart defects research
- Biochemical and Molecular Research
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Signaling Pathways in Disease
- Epigenetics and DNA Methylation
- DNA and Nucleic Acid Chemistry
- HIV Research and Treatment
- Aldose Reductase and Taurine
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Spondyloarthritis Studies and Treatments
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
University of Colorado Boulder
2003-2024
Amgen (United States)
2018-2020
Stanford University
2011-2012
Stratford University
2011
University of South Australia
2010
University of California, San Francisco
2009
University of Southern California
2007-2009
University of Hong Kong
1986
Royal Victoria Infirmary
1986
Birmingham and Midland Eye Centre
1986
Genes are not simply turned on or off, but instead their expression is fine-tuned to meet the needs of a cell. How genes modulated so precisely well understood. The glucocorticoid receptor (GR) regulates target by associating with specific DNA binding sites, sequences which differ between genes. Traditionally, these sites have been viewed only as docking sites. Using structural, biochemical, and cell-based assays, we show that GR sequences, differing little single base pair, differentially...
Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) has been identified in multiple genome-wide association studies (GWAS) as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). On the basis of this genetic evidence, we developed anti-GIPR antagonistic antibodies potential therapeutic strategy for treatment observed that mouse anti-murine antibody (muGIPR-Ab) body weight gain, improved metabolic parameters, was associated with...
GATA transcription factors regulate during development and differentiation by recognizing distinct sites with a tandem of two conserved zinc fingers, mediating long-range DNA looping. However, the molecular basis these processes is not well understood. Here, we determined three crystal structures full DNA-binding domain (DBD) human GATA3 protein, which contains both in complex different sites. In one structure, fingers wrap around palindromic site, cooperatively enhancing binding affinity...
Among all T and NK cell subsets, regulatory (Treg) cells typically respond to the lowest concentrations of IL-2 due elevated surface expression IL-2R alpha chain (CD25) high affinity receptor (IL-2R) complex. This enhanced sensitivity forms basis for low-dose (LD) therapy treatment inflammatory diseases, where efficacy correlates with increased Treg number functional markers. Despite strong preclinical support this approach, moderate variable clinical has raised concerns that adequate...
Glutamine-rich sequences exist in a wide range of proteins across multiple species. A subset glutamine-rich has been shown to form amyloid fibers implicated human diseases. The physiological functions these sequence motifs are not well understood, partly because the lack structural information. Here we have determined high-resolution structure domain from histone deacetylase 4 (HDAC4) by x-ray crystallography. HDAC4 (19 glutamines 68 residues) folds into straight α-helix that assembles as...
Two sisters had primary biliary disease and associated autoimmune thyroiditis with high titres of mitochondrial other autoantibodies. Their deceased mother possibly suffered from similar disorders. In the same family two brothers multiple reactions, including antibodies, but liver function tests gave normal results. Ten close relatives were investigated. Australia antigen was not found in proband or her relatives.
Abstract Class IIa Histone deacetylases (HDACs), including HDAC4, 5, 7 and 9, play key roles in multiple important developmental differentiation processes. Recent studies have shown that class HDACs exert their transcriptional repressive function by interacting with tissue-specific transcription factors, such as members of the myocyte enhancer factor 2 (MEF2) family factors. However, molecular mechanism is not well understood. In this study, we determined crystal structure an HDAC4–MEF2A–DNA...
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in regulating glucose and lipid metabolism. GIP receptor (GIPR) antagonism believed to offer therapeutic potential for various metabolic diseases. Pharmacological intervention of GIPR, however, has limited success due lack effective antagonistic reagents. Previously we reported the discovery two mouse anti-murine GIPR monoclonal antibodies (mAbs) with distinctive properties rodent models. Here, report detailed...
Histocompatibility antigen (HLA A, B and DR) serotyping was performed on 65 patients with motor neuron disease in the northern region of England compared to a large control population from Newcastle upon Tyne area. Thirty two had amyotrophic lateral sclerosis, 17 progressive bulbar palsy 16 muscular atrophy. Ten more slowly course. No significant HLA associations were observed patients. Subdivision by clinical course their did not reveal any associations. Forty six area reduced frequency DR4...
Abstract IL-4 supports the differentiation and function of B T cells, but also induces a response in virtually all cell types. Lymphocytes express mostly type I receptor (IL-4Ra common gamma (CG) chains), non-hematopoietic cells primarily II IL-13Ra1 chains; for IL-13), while other leukocytes both. We have engineered human variants with up to 3-logs higher affinity CG, or 2-logs increased binding IL-13Ra1. Binding these did not perturb orientation. Selected were tested on various lines...