A5101552475- Parathyroid Disorders and Treatments
- Genetic Syndromes and Imprinting
- Cell Adhesion Molecules Research
- Bone health and treatments
- Renal and related cancers
- Magnesium in Health and Disease
- Fibroblast Growth Factor Research
- Advanced Glycation End Products research
- Bone and Dental Protein Studies
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Renal Diseases and Glomerulopathies
- Platelet Disorders and Treatments
- Vitamin D Research Studies
- Bone Metabolism and Diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Connective tissue disorders research
- Biomedical Research and Pathophysiology
- Protein Kinase Regulation and GTPase Signaling
- Erythrocyte Function and Pathophysiology
- Pancreatitis Pathology and Treatment
- TGF-β signaling in diseases
- Liver Disease Diagnosis and Treatment
- Advanced biosensing and bioanalysis techniques
- Medical Imaging and Pathology Studies
Florida College
2022-2024
University of Florida
2022-2024
AVEO Oncology (United States)
2024
Sanofi (United States)
2018-2024
University College London
2024
Genesys (United States)
2012-2022
Sanofi (United Kingdom)
2022
Shanghai Jiao Tong University
2020
Ruijin Hospital
2020
Temple University Hospital
2014-2018
The regulation of the phosphaturic factor fibroblast growth 23 (FGF23) is not well understood. It was found that administration 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) to mice rapidly increased serum FGF23 concentrations from a basal level 90.6 ± 8.1 213.8 14.6 pg/ml at 8 h (mean SEM; P < 0.01) and resulted in four-fold increase transcripts bone, predominate site expression. In Hyp-mouse homologue X-linked hypophosphatemic rickets, 1,25(OH)2D3 further circulating levels. Gcm2 null mice, low...
Inactivating mutations of Phex cause X-linked hypophosphatemia (XLH) by increasing levels a circulating phosphaturic factor. FGF23 is candidate for this Elevated serum correlate with the degree in XLH, suggesting that loss function disorder results either diminished degradation and/or increased biosynthesis FGF23. To establish mechanisms whereby regulates FGF23, we assessed Phex-dependent hydrolysis recombinant vitro and measured fgf23 message Hyp mouse homologue XLH. In COS-7 cells,...
Inactivating mutations of the PHEX (phosphate-regulating gene with homologies to endopeptidases on X chromosome) endopeptidase, disease-causing in X-linked hypophosphatemia (XLH), results increased circulating levels fibroblastic growth factor-23 (FGF23), a bone-derived phosphaturic factor. To determine causal role FGF23 XLH, we generated combined Fgf23-deficient enhanced green fluorescent protein (eGFP) reporter and Phex-deficient Hyp mouse model (Fgf23(+/-)/Hyp). eGFP expression was...
Obesity increases the risk of adverse outcomes during acute critical illnesses such as burns, severe trauma, and pancreatitis. Although individuals with more body fat higher serum cytokines lipase are likely to experience problems, roles that these characteristics play not clear. We used pancreatitis a representative disease investigate effects obesity on local organ function systemic processes. In obese humans, we found an increase in volume intrapancreatic adipocytes was associated...
MicroRNA-21 (miR-21) contributes to the pathogenesis of fibrogenic diseases in multiple organs, including kidneys, potentially by silencing metabolic pathways that are critical for cellular ATP generation, ROS production, and inflammatory signaling. Here, we developed highly specific oligonucleotides distribute kidney inhibit miR-21 function when administered subcutaneously evaluated therapeutic potential these anti-miR-21 chronic disease. In a murine model Alport nephropathy, did not...
Abstract Chronic kidney disease–mineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features CKD-MBD may occur early disease progression are associated with changes osteocyte function. To identify bone, we utilized jck mouse, a genetic model polycystic exhibits progressive renal disease. At 6 weeks age, mice have normal function no but...
Fibroblastic growth factor 23 (FGF23) is a circulating phosphaturic hormone. Inactivating mutations of the endopeptidase PHEX or SIBLING protein DMP1 result in equivalent intrinsic bone mineralization defects and increased Fgf23 expression osteocytes. The mechanisms whereby regulate are unknown. We examined possibility that through common pathway by analyzing phenotype compound Phex Dmp1 mutant mice (Hyp/Dmp1–/–). Compared to single-mutant littermates, compound-mutant Hyp/Dmp1–/– displayed...
We investigated if the circulating levels of phosphaturic factor FGF23 are elevated in subjects with XLH. Although we failed to find a statistically significant increase, were significantly correlated degree hypophosphatemia In contrast, markedly increased ESRD and inversely hyperphosphatemia.Inactivating mutations PHEX cause renal phosphate wasting X-linked hypophosphatemic rickets (XLH) because accumulation hormone called phosphatonin. The recent discovery that is autosomal dominant raises...
Fibroblastic growth factor 23 (FGF23) regulates renal phosphate reabsorption and 1alpha-hydroxylase activity. Ablation of FGF23 results in elevated serum phosphate, calcium, 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D] levels; vascular calcifications; early death. For determination the independent roles hyperphosphatemia excess vitamin D activity on observed phenotypic abnormalities, null mice were fed a phosphate- or D-deficient diet. The phosphate-deficient diet corrected hyperphosphatemia,...
High-mobility group box 1 (HMGB1) is a 30-kDa DNA-binding protein that displays proinflammatory cytokine-like properties. HMGB1-dependent inflammatory processes have been demonstrated in models of sterile injury, including ischemia-reperfusion injury and hemorrhagic shock. Here, we tested the hypothesis systemic response associated remote organ occur after peripheral tissue are highly dependent on HMGB1. Toll-like receptor 4 (TLR4) wild-type (WT) mice subjected to bilateral femur fracture...
The treatment for X-linked hypophosphatemia (XLH) with phosphate and calcitriol can be complicated by secondary hyperparathyroidism nephrocalcinosis. Furthermore, vitamin D stimulate FGF23 production, the pathogenic factor causing XLH. We investigated in XLH patients: 1) whether calcimimetic agent, cinacalcet, will block rise parathyroid hormone (PTH) caused administration; 2) oral increases levels.Eight subjects were given a single dose of phosphate, followed next day combined cinacalcet....
Fibroblast growth factor-23 (FGF23) levels are elevated in ESRD and have been associated with adverse outcomes. The effects of various treatments for secondary hyperparathyroidism on FGF23 not examined a clinical trial.We assessed intact 91 subjects over the course ACHIEVE trial, which was designed to compare escalating doses Cinacalcet plus fixed low-dose calcitriol analogs (Cinaclcet-D) titration alone (Flex-D) suppress parathyroid hormone. Between-group within-group changes...
Fibroblast growth factor 23 (FGF23) is a phosphaturic that suppresses both sodium-dependent phosphate transport and production of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] in the proximal tubule. In vitro studies suggest FGFR3 physiologically relevant receptor for FGF23 kidney, but this has not been established vivo. Here, immunohistochemical analysis mouse kidney revealed tubule expresses FGF 3 (FGFR3) FGFR1, FGFR2, or FGFR4. Compared with wild-type mice, Hyp which have elevated circulating...
Star polymers with poly(ethylene glycol) (PEG) arms and a degradable cationic core were synthesized by the atom transfer radical copolymerization (ATRP) of methyl ether methacrylate macromonomer (PEGMA), 2-(dimethylamino)ethyl (DMAEMA), disulfide dimethacrylate (cross-linker, SS) via an "arm-first" approach. The star had diameter ∼15 nm degraded under redox conditions glutathione treatment into individual polymeric chains due to cleavage cross-linker, as confirmed dynamic light scattering....
To understand the role of calcium-sensing receptor (CasR) in skeleton, we used a genetic approach to ablate parathyroid glands and remove confounding effects elevated hormone (PTH) CasR-deficient mice. CasR deficiency was transferred onto glial cells missing 2–deficient (Gcm2-deficient) background by intercrossing CasR- Gcm2-deficient Superimposed Gcm2 rescued perinatal lethality mice association with ablation correction severe hyperparathyroidism. In addition, double homozygous demonstrated...
High-mobility group box 1 (HMGB1), a cytokine-like proinflammatory protein, is secreted by activated macrophages and released necrotic cells. We hypothesized that immunostimulated enterocytes might be another source for this mediator. Accordingly, Caco-2 cells or primary mouse intestinal epithelial (IECs) were incubated with "cytomix" (a mixture of TNF, IL-1beta, IFN-gamma) various periods. HMGB1 in cell culture supernatants was detected Western blot analysis visualized the use fluorescence...
To understand the role of calcium-sensing receptor (CasR) in skeleton, we used a genetic approach to ablate parathyroid glands and remove confounding effects elevated hormone (PTH) CasR-deficient mice. CasR deficiency was transferred onto glial cells missing 2–deficient (Gcm2-deficient) background by intercrossing CasR- Gcm2-deficient Superimposed Gcm2 rescued perinatal lethality mice association with ablation correction severe hyperparathyroidism. In addition, double homozygous demonstrated...
Autosomal recessive hypophosphatemic rickets (ARHR), which is characterized by renal phosphate wasting, aberrant regulation of 1alpha-hydroxylase activity, and rickets/osteomalacia, caused inactivating mutations dentin matrix protein 1 (DMP1). ARHR resembles autosomal dominant (ADHR) X-linked hypophosphatemia (XLH), hereditary disorders respectively cleavage-resistant the phosphaturic factor FGF23 PHEX that lead to increased production osteocytes in bone. Circulating levels are its Dmp1-null...
We used gene array analysis of cortical bone to identify Phex-dependent transcripts associated with abnormal Fgf23 production and mineralization in Hyp mice. found evidence that elevation expression osteocytes is increments Fgf1, Fgf7, Egr2 decrements Sost, an inhibitor the Wnt-signaling pathway, were observed bone. beta-Catenin levels increased bone, TOPflash luciferase reporter assay showed transcriptional activity Hyp-derived osteoblasts, consistent Wnt activation. Moreover, activation...