A5079183709- Renal cell carcinoma treatment
- Prostate Cancer Treatment and Research
- Cancer Genomics and Diagnostics
- Pharmacogenetics and Drug Metabolism
- Renal Transplantation Outcomes and Treatments
- Lung Cancer Treatments and Mutations
- Radiopharmaceutical Chemistry and Applications
- Quinazolinone synthesis and applications
- Renal and related cancers
- Acute Lymphoblastic Leukemia research
- Pharmaceutical studies and practices
- Pharmacological Effects and Toxicity Studies
- Cancer therapeutics and mechanisms
- Bladder and Urothelial Cancer Treatments
- Colorectal Cancer Treatments and Studies
- Pulmonary Hypertension Research and Treatments
- Epigenetics and DNA Methylation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Histone Deacetylase Inhibitors Research
- Angiogenesis and VEGF in Cancer
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Protein Degradation and Inhibitors
- Hematopoietic Stem Cell Transplantation
- Renal Diseases and Glomerulopathies
University of North Carolina at Chapel Hill
2016-2025
UNC Lineberger Comprehensive Cancer Center
2016-2024
University of North Carolina Health Care
2020-2024
University of North Carolina Hospitals
2017-2022
St. Jude Children's Research Hospital
2015
University of Colorado Health
2009-2011
Familial pulmonary arterial hypertension (PAH) is associated with mutations in bone morphogenetic protein type II receptor (BMPR2). Many of these occur the BMPR2 tail domain, leaving SMAD functions intact. To determine vivo consequences domain mutation, we created a smooth muscle-specific doxycycline-inducible mutation an arginine to termination at amino acid 899. When SM22-rtTA x TetO 7 -BMPR2 R899X mice had transgene induced for 9 wk, starting 4 wk age, they universally developed vascular...
We describe SGC-GAK-1 (11), a potent, selective, and cell-active inhibitor of cyclin G-associated kinase (GAK), together with structurally related negative control SGC-GAK-1N (14). 11 was highly selective in an vitro kinome-wide screen, but cellular engagement assays defined RIPK2 as collateral target. identified 18 potent lacking GAK activity. Together, this chemical probe set can be used to interrogate biology.
Pulmonary arterial hypertension (PAH) is thought to be driven by dysfunction of pulmonary vascular microendothelial cells (PMVEC). Most hereditary PAH associated with BMPR2 mutations. However, the physiologic and molecular consequences expression mutations in PMVEC are unknown.In vivo experiments were performed on adult mice conditional endothelial-specific truncation mutation Bmpr2delx4+, age-matched transactivator-only as controls. Phenotype was assessed RVSP, counts muscularized vessels...
Idiopathic pulmonary arterial hypertension (IPAH) in human patients is associated with mutations type 2 receptor for the bone morphogenic protein pathway (BMPR2). Mice expressing an inducible dominant negative form of BMPR2 smooth muscle develop elevated right ventricular pressures when transgene activated. We hypothesized that transcriptional changes these mice may allow insight into early molecular events leading to IPAH. Microarray analysis was used examine induced whole lung by loss...
Extreme obesity—also referred to as severe, grade III, or morbid obesity—is defined a body mass index (BMI) > 40 kg/m2, and occurs in 7.7% of the adult US population.1.Hales C.M. Fryar C.D. Carroll M.D. Freedman D.S. Ogden C.L. Trends obesity severe prevalence us youth adults by sex age, 2007‐2008 2015‐2016.JAMA. 2018; 319: 1723-5Crossref PubMed Scopus (1043) Google Scholar This translates nearly 20 million extremely obese living US.2.Data Statistics about U.S. [Accessed 2018 November 23]...
Statins may potentiate the effects of anti-hormonal agents for metastatic castration-resistant prostate cancer (mCRPC) through further disruption essential steroidogenic processes. We investigated statin use on clinical outcomes in patients with mCRPC receiving abiraterone or enzalutamide.This was a retrospective multicenter study including that received enzalutamide mCRPC. The effect concurrent evaluated. associations statins early (≤12 weeks) prostate-specific antigen (PSA) declines (>...
Quinoline- and quinazoline-based kinase inhibitors of the epidermal growth factor receptor (EGFR) have been used to target non-small cell lung cancer (NSCLC) chordomas with varying amounts success. We designed prepared compounds probe several key structural features including an interaction Asp855 within EGFR DGF motif interactions active site water network. engagement was then evaluated in a cellular assay, profiled representative models NSCLC chordomas. In addition, structure-activity...
Abstract Molecular markers of sorafenib efficacy in patients with metastatic renal cell carcinoma (mRCC) are not available. The purpose this study was to discover genetic survival mRCC treated sorafenib. Germline variants from 56 genes were genotyped 295 mRCC. Variant-overall (OS) associations tested multivariate regression models. Mechanistic studies conducted validate clinical associations. VEGFA rs1885657, ITGAV rs3816375, and WWOX rs8047917 (sorafenib arm), FLT4 rs307826 rs3024987...
Background : Altered concentrations of ghrelin, motilin, and cholecystokinin (CCK) may contribute to gastric hypomotility. The aims this study were evaluate the these hormones in patients tolerant intolerant nutrition, assess influence prokinetic therapy on hormone concentrations, determine associations between mediators emptying, whether inflammation influences their concentrations. Methods Post hoc analyses 2 prospective studies that enrolled 20 critically ill with an aspirated residual...
Tacrolimus exhibits high inter-patient pharmacokinetics (PK) variability, as well a narrow therapeutic index, and therefore requires drug monitoring. Germline mutations in cytochrome P450 isoforms 4 5 genes (CYP3A4/5) the ATP-binding cassette B1 gene (ABCB1) may contribute to interindividual tacrolimus PK which impact clinical outcomes among allogeneic hematopoietic stem cell transplantation (HSCT) patients. In this study, 252 adult patients who received for acute graft versus host disease...