A5048068162- Growth Hormone and Insulin-like Growth Factors
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Pancreatic function and diabetes
- Platelet Disorders and Treatments
- Colorectal Cancer Screening and Detection
- Monoclonal and Polyclonal Antibodies Research
- Histone Deacetylase Inhibitors Research
- Protease and Inhibitor Mechanisms
- Heparin-Induced Thrombocytopenia and Thrombosis
- Radiomics and Machine Learning in Medical Imaging
- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- Cancer, Lipids, and Metabolism
- Blood groups and transfusion
- Mass Spectrometry Techniques and Applications
- Digestive system and related health
- Nutrition, Genetics, and Disease
- Antiplatelet Therapy and Cardiovascular Diseases
- Polyamine Metabolism and Applications
- Cancer, Stress, Anesthesia, and Immune Response
- Peptidase Inhibition and Analysis
- Erythrocyte Function and Pathophysiology
- Pharmacological Effects and Toxicity Studies
University of Oxford
2023
University of Massachusetts Boston
2016-2023
CSIRO Health and Biosecurity
2008-2018
Commonwealth Scientific and Industrial Research Organisation
2005-2016
Cambridge Health Alliance
2016
Tufts University
2016
York University
2016
Harvard University
2015
Health Sciences and Nutrition
2000-2012
Animal, Food and Health Sciences
2012
Abstract The insulin receptor (IR) lacking the alternatively spliced exon 11 (IR-A) is preferentially expressed in fetal and cancer cells. IR-A has been identified as a high-affinity for IGF-II but not IGF-I, which it binds with substantially lower affinity. Several cell types that express also overexpress IGF-II, suggesting possible autocrine proliferative loop. To determine regions of IGF-I responsible this differential affinity, chimeras were made where C D domains exchanged between...
The insulin receptor (IR) and the type-1 insulin-like growth factor (IGF1R) are homologous multidomain proteins that bind IGF with differing specificity. Here we report crystal structure of first three domains (L1-CR-L2) human IR at 2.3 A resolution compare it previously determined corresponding fragment IGF1R. most important differences seen between two receptors in regions governing ligand is corner ligand-binding surface L1 domain, where side chain F39 forms part binding involving second...
The majority of colorectal cancer (CRC) cases are preventable by early detection and removal precancerous polyps. Even though CRC is the second most common internal in Australia, only 30 per cent population considered to have risk factors participate stool-based test screening programs. Evidence indicates a robust, blood-based, diagnostic assay would increase compliance. A number potential blood-based protein biomarkers for been reported, but all lack sensitivity or specificity use as...
The insulin-like growth factors (insulin-like factor I [IGF-I] and IGF-II) exert important effects on growth, development, differentiation through the IGF-I receptor (IGF-IR) transmembrane tyrosine kinase. insulin (IR) is structurally related to IGF-IR, at high concentrations, IGFs can also activate IR, in spite of their generally low affinity for latter. Two mechanisms that facilitate cross talk between IGF ligands IR physiological concentrations have been described. first these existence...
Short chain fatty acids (SCFA), principally butyrate, propionate, and acetate, are produced in the gut through fermentation of dietary fiber by colonic microbiotica. Butyrate particular is preferred energy source for cells mucosa has been demonstrated to induce apoptosis colorectal cancer cell lines. We have used proteomics, specifically 2D-DIGE mass spectrometry, identify proteins involved butyrate-induced HCT116 also development butyrate insensitivity its derivative, HCT116-BR cells. The...
We measured the complement-dependent cytotoxic activity of serum in 60 patients with pernicious anemia. Canine gastric mucosal cells served as indicator cytotoxicity, which was expressed a percentage maximal effect produced by cytolytic agent (Triton X-100). Serum from anemia showed higher average (11.8 +/- 10.3 per cent, P less than 0.001) 29 systemic lupus erythematosus (1.0 1.8 cent), 10 scleroderma (0.1 0.1 rheumatoid arthritis (0.6 0.6 22 multiple sclerosis (0.4 1.2 and 23 chronic...
Insulin-like growth factor (IGF) binding to the type 1 IGF receptor (IGF1R) elicits mitogenic effects, promotion of differentiation and protection from apoptosis. This study has systematically measured IGF1R affinities IGF-I, IGF-II 14 analogues a recombinant high-affinity form using BIAcore technology. The assessed could be divided into two groups: (a) those designed investigate IGF-binding protein, which exhibited IGF1R-binding similar IGF-I or IGF-II; (b) generated probe interactions with...
Elevated expression of insulin-like growth factor-II (IGF-II) is frequently observed in a variety human malignancies, including breast, colon, and liver cancer. As IGF-II can deliver mitogenic signal through both IGF-IR an alternately spliced form the insulin receptor (IR-A), neutralizing biological activity this factor directly potential alternative option to IGF-IR-directed agents. Using Fab-displaying phage library biotinylated precursor (1-104 amino acids) as target, we isolated Fabs...
To determine the usefulness of brain-derived neurotrophic factor (BDNF) as a diagnostic biomarker for colorectal cancer (CRC).ELISA immunoassay was used to examine BDNF concentrations in sera two different retrospective cohorts consisting CRC patients and age/gender matched controls. Cohort 1 consisted 99 controls 97 patients, whereas cohort 2 47 91 patients.In 1, median concentration significantly (p< 0.0001) lower patient samples (18.8 ng/mL, range 4.0-56.5 ng/mL) than control (23.4...
Clinical practice guidelines abound. The recommendations contained in these are used not only to make decisions about the care of individual patients but also as standards rate physician "quality." Physicians' confidence is based on supposition that there a rigorous, objective process for developing best available evidence. Though voluntary development exist, guideline unregulated and quality many low. In addition, few tools assess time consuming designed researchers, clinicians. Few...
To investigate the interaction of insulin-like growth factor (IGF) ligands with type 1 receptor (IGF-1R), we have generated two soluble variants IGF-1R. We recombinantly expressed ectodomain IGF-1R or fused this domain to constant from Fc fragment mouse immunoglobulin. The ligand binding properties these IGF-1Rs for IGF-I and IGF-II were investigated using conventional competition assays BIAcore biosensor technology. In assays, both bound similar affinities a 5-fold lower affinity than that...
S ummary . Platelet‐associated IgG (PA IgG) of washed platelets 20 normal controls and 45 thrombocytopenic patients was measured by radioimmunoassay related to total platelet protein content. Mean values (±2 SD) for normals were 4.4 ± 3.5 fg per (fg IgG/pl), 2.1 1.0 pg (pg protein/pl) a ratio g 1.8 mg IgG/g protein. Patients could be divided into two groups: Group I (31) with ratios either (16) or raised (15) IgG/pl, II (14) both IgG/pl raised. Of the 21 idiopathic thrombocytopenia (ITP), 13...
Sessile serrated adenomas/polyps (SSA/P) are now recognised precursors of colorectal cancer (CRC) including cancers harbouring somatic BRAF (V600E) mutations. While the morphological diagnostic criteria SSA/P have been established, distinguishing between small/early and microvesicular hyperplastic polyps (MVHP) is challenging may not be possible in routine practice.Gene expression profiling MVHP (n=5, all V600E wild-type) mutant) samples was performed. Quantitative reverse...
Site-directed mutagenesis has been used to remove 15 of the 18 potential N-linked glycosylation sites, in 16 combinations, from human exon 11-minus receptor isoform. The three sites not mutated were asparagine residues 25, 397 and 894, which are known be important biosynthesis or function. effects these mutations on proreceptor processing into alpha beta subunits, cell-surface expression, insulin binding autophosphorylation assessed Chinese hamster ovary cells. double mutants 16+78, 16+111,...
LFA-1, an antigen involved in cytolytic T lymphocyte-mediated killing, and Mac-1, the receptor for complement component C3bi, constitute a family of structurally functionally related cell surface glycoproteins cellular interactions. In both mouse man, Mac-1 (OKM1) LFA-1 share common 95-kDa beta subunit but are distinguished by their alpha chains, which have different distributions, apparent molecular masses (165 177 kDa, respectively), peptide maps. We report isolation genomic clone from...