A5081805141- Scoliosis diagnosis and treatment
- Cardiac Arrhythmias and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Spinal Fractures and Fixation Techniques
- Cardiac pacing and defibrillation studies
- Cardiac electrophysiology and arrhythmias
- Congenital Heart Disease Studies
- Congenital Diaphragmatic Hernia Studies
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Cardiovascular Syncope and Autonomic Disorders
- Cancer-related gene regulation
- Chemical Synthesis and Analysis
- Reproductive Physiology in Livestock
- Melanoma and MAPK Pathways
- Cardiovascular Effects of Exercise
- Cancer Mechanisms and Therapy
- Pectus Deformity Diagnosis and Treatment
- Atrial Fibrillation Management and Outcomes
- 14-3-3 protein interactions
- Pelvic and Acetabular Injuries
- Peptidase Inhibition and Analysis
- Cardiac Arrest and Resuscitation
- Ultrasound in Clinical Applications
- Cerebrospinal fluid and hydrocephalus
Queensland Children’s Hospital
2016-2025
The University of Queensland
2019-2024
Mater Misericordiae Hospital
2024
Bendigo Health
2022-2024
Children's Hospital of Philadelphia
2013-2023
Abeona Therapeutics (United States)
2023
Pennsylvania State University
2023
University of Colorado Anschutz Medical Campus
2023
Constellation Pharmaceuticals (United States)
2012-2022
Queen's University
2022
Although several studies describe the 22q11.2 deletion, population-based data are scant. Such needed to evaluate properly impact, distribution, and clinical presentation of deletion in population. Our goals were assess birth prevalence its associated phenotype impact on occurrence heart defects.We evaluated infants who born from 1994 through 1999 women resided metropolitan Atlanta. We matched records Metropolitan Atlanta Congenital Defects Program (a registry with active case ascertainment),...
• Thoracic insufficiency syndrome is the inability of thorax to support normal respiration or lung growth. The rare condition fused ribs and congenital scoliosis may result in a three-dimensional thoracic deformity with adverse effects on growth function development syndrome. defined by two characteristics: normal, stable volume ability change that volume. Volume depends width depth rib cage, spine provides height. volume, termed function, provided diaphragm secondary muscles respiration. On...
Abstract Activation of protein kinase Cβ (PKCβ) has been repeatedly implicated in tumor-induced angiogenesis. The PKCβ-selective inhibitor, Enzastaurin (LY317615.HCl), suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. PKCβ now also tumor cell proliferation, apoptosis, invasiveness. Herein, we show that a direct effect on human cells, inducing apoptosis suppressing the proliferation cultured cells. treatment phosphorylation GSK3βser9,...
Protein arginine methyltransferases (PRMTs) play important roles in several cellular processes, including signaling, gene regulation, and transport of proteins nucleic acids, to impact growth, differentiation, proliferation, development. PRMT5 symmetrically di-methylates the two-terminal ω-guanidino nitrogens residues on substrate proteins. acts as part a multimeric complex concert with variety partner that regulate its function specificity. A core component these complexes is WD40 protein...
Polycomb repressive complex 2 (PRC2) has been shown to play a major role in transcriptional silencing part by installing methylation marks on lysine 27 of histone 3. Dysregulation PRC2 function correlates with certain malignancies and poor prognosis. EZH2 is the catalytic engine thus represents key candidate oncology target for pharmacological intervention. Here we report optimization our indole-based inhibitor series that led identification CPI-1205, highly potent (biochemical IC50 = 0.002...
In recent years, inhibition of the interaction between bromodomain and extra-terminal domain (BET) family chromatin adaptors acetyl-lysine residues on has emerged as a promising approach to regulate expression important disease-relevant genes, including MYC, BCL-2, NF-κB. Here we describe identification characterization potent selective benzoisoxazoloazepine BET inhibitor that attenuates BET-dependent gene in vivo, demonstrates antitumor efficacy an MV-4-11 mouse xenograft model, is...
Loss-of-function mutations in the retinoblastoma gene RB1 are common several treatment-refractory cancers such as small-cell lung cancer and triple-negative breast cancer. To identify drugs synthetic lethal with mutation (RB1 mut), we tested 36 cell-cycle inhibitors using a cell panel profiling approach optimized to discern cytotoxic from cytostatic effects. Inhibitors of Aurora kinases AURKA AURKB showed strongest association this assay. LY3295668, an inhibitor over 1,000-fold selectivity...
Background: Thoracic insufficiency syndrome is the inability of thorax to support normal respiration or lung growth and seen in patients who have severe congenital scoliosis with fused ribs. Traditional spinal surgery does not directly address this syndrome. Methods: Twenty-seven associated ribs concave hemithorax had an opening wedge thoracostomy primary longitudinal lengthening use a chest-wall distractor known as vertical, expandable prosthetic titanium rib. Repeat lengthenings prosthesis...
ABSTRACT To contribute to an understanding of the roles and mechanisms action Wnts in early vertebrate development, we have characterized normal expression Xenopus laevis Wnt-5A, investigated consequences misexpression this putative signalling factor. Xwnt-5A transcripts are expressed throughout enriched both anterior posterior regions embryos at late stages where they found primarily ectoderm, with lower levels mesoderm. Overexpression leads complex mal-formations distinct from those...
Background: Children with congenital thoracic scoliosis associated fused ribs a unilateral unsegmented bar adjacent to convex hemivertebrae will invariably have curve progression without treatment. Surgery has been thought negligible growth-inhibition effect on the spine in such patients because it assumed that concave side of and do not grow, but we are unaware any conclusive studies regarding this assumption. Methods: The changes length sides, anterior posterior vertebral edges, arch, bars...
Background The surgical treatment of severe early-onset scoliosis (EOS) is controversial. Obtaining and maintaining deformity correction, achieving adequate spinal growth, allowing lung development, the high complication rate make very challenging. Growing rods are most common method management. Methods Currently, there 3 systems being used for EOS: single growing rod, dual rods, vertical expandable titanium prosthetic rib implant. Each system has its advantages disadvantages. These...
The Mustard operation corrects the effects of congenital transposition great arteries by creating an intraarterial baffle to direct pulmonary venous blood tricuspid orifice and systemic mitral orifice. To identify long-term this procedure, we followed 372 patients with complete who survived for at least three months. mean follow-up period was 4.5 years (range, 0.4 15.9); age 2.0 years. Mean resting heart rates were consistently lower than those age-matched normal children. Seventy-six per...
Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination SAR in both enzyme- and cell-based vitro assays resulted emergence two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at active site has been established by successful cocrystallization X-ray analysis potent with TbetaR-I domain.
A novel cyclic GRF analog, cyclo(Asp 8 ‐Lys 12 )‐[Asp ,Ala 15 ]‐GRF(1‐29)‐ NH 2 , i.e. cyclo 8.12 [Asp was synthesized by the solid phase procedure and found to retain significant biological activity. Solid cyclization of Asp Lys proceeded rapidly (∼2h) using BOP reagent. Substitution Ala with d ‐Ala and/or ‐terminal replacement (des ‐Tyr 1 or N ‐MeTyr ) in system resulted highly potent analogs that were also active vivo. Conformational analysis (circular dichroism molecular dynamics...
To investigate the development of HLA-DR-associated autoimmune diseases, we generated transgenic (Tg) mice with HLA-DRA-IE alpha and HLA-DRB1*0401-IE beta chimeric genes. The transgene-encoded proteins consisted antigen-binding domains from HLA-DRA HLA-DRB1*0401 molecules remaining IE(d)-alpha IE(d)-beta chains. showed same specificity as molecules, were functional in presenting antigens to T cells. Tg backcrossed MHC class II-deficient (IA beta-, IE alpha-) eliminate any effect endogenous...