A5084331990- Protein Degradation and Inhibitors
- Muscle Physiology and Disorders
- Receptor Mechanisms and Signaling
- Phagocytosis and Immune Regulation
- Pancreatic and Hepatic Oncology Research
- Congenital heart defects research
- Computational Drug Discovery Methods
- Malaria Research and Control
- Parasitic Infections and Diagnostics
- Cardiomyopathy and Myosin Studies
- Pancreatitis Pathology and Treatment
- Endometriosis Research and Treatment
- Lysosomal Storage Disorders Research
- RNA Research and Splicing
- Galectins and Cancer Biology
- HIV/AIDS drug development and treatment
- Uterine Myomas and Treatments
- Neurogenetic and Muscular Disorders Research
- Endometrial and Cervical Cancer Treatments
- Peptidase Inhibition and Analysis
- Helicobacter pylori-related gastroenterology studies
- Electroconvulsive Therapy Studies
- Trypanosoma species research and implications
- Pneumocystis jirovecii pneumonia detection and treatment
- Telomeres, Telomerase, and Senescence
Saint Louis University
2013-2024
University of Rochester Medical Center
2019
Ultragenyx Pharmaceutical (United States)
2019
University of Washington
2019
Fred Hutch Cancer Center
2019
Walter Reed National Military Medical Center
2014
Facioscapulohumeral muscular dystrophy (FSHD) is characterized by misexpression of the double homeobox 4 (DUX4) developmental transcription factor in mature skeletal muscle, where it responsible for muscle degeneration. Preventing expression DUX4 mRNA a disease-modifying therapeutic strategy with potential to halt or reverse course disease. We previously reported that agonists
Facioscapulohumeral dystrophy (FSHD) is a progressive muscle disease caused by mutations that lead to epigenetic derepression and inappropriate transcription of the double homeobox 4 (DUX4) gene in skeletal muscle. Drugs enhance repression DUX4 prevent its expression cells therefore represent candidate therapies for FSHD.We screened an aggregated chemical library enriched compounds with activities Pharmakon 1600 composed have reached clinical testing identify molecules decrease as monitored...
Apolipoprotein L1 (ApoL1) is a human serum protein conferring resistance to African trypanosomes, and certain ApoL1 variants increase susceptibility some progressive kidney diseases. has been hypothesized function like pore-forming colicin reported have permeability effects on both intracellular plasma membranes. Here, gain insight into how may in vivo, we used vesicle-based ion permeability, direct membrane association, intrinsic fluorescence study the activities of purified recombinant...
Given the threat of drug resistance, there is an acute need for new classes antimalarial agents that act via a unique mechanism action relative to currently used drugs. We have identified set druglike compounds within Tres Cantos Anti-Malarial Set (TCAMS) which likely inhibition Plasmodium aspartic protease. Structure–activity relationship analysis and optimization these aminohydantoins demonstrate are potent nanomolar inhibitors proteases PM-II PM-IV one or more other proteases....
Background & AimsPancreatic stellate cells (PSCs) regulate the development of chronic pancreatitis (CP) and are activated by cytokine transforming growth factor β (TGFB). Integrins αv family promote TGFB signaling in mice, probably interacting with Arg-Gly-Asp (RGD) sequence latency-associated peptide, which frees to bind its cellular receptors. However, little is known about role integrins CP. We investigated effects small-molecule integrin inhibitors a mouse model CP.MethodsWe induced CP...
Our previous work identified compound
Facioscapulohumeral muscular dystrophy (FSHD) is a degenerative muscle disease caused by loss of epigenetic silencing and ectopic reactivation the embryonic double homeobox protein 4 gene (DUX4) in skeletal muscle. The p38 MAP kinase inhibitor losmapimod currently being tested FSHD clinical trials due to finding that inhibition suppresses DUX4 expression preclinical models. However, role regulating at different myogenic stages has not been investigated. We used genetic pharmacologic tools...
Abstract Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle wasting disease caused by misexpression of the Double Homeobox 4 (DUX4) transcription factor in skeletal muscle. While epigenetic derepression D4Z4 macrosatellite repeats recognized to cause DUX4 FSHD, factors promoting are unknown. Here, we show that SIX ( sine oculis ) factors, critical during embryonic development, differentiation, regeneration and homeostasis, key regulators expression FSHD cells. In this...
Facioscapulohumeral muscular dystrophy (FSHD) is a common and progressive muscle wasting disease that characterized by weakness often first noticed in the face, shoulder girdle upper arms before progressing to lower limb muscles. FSHD caused misexpression of Double Homeobox 4 (DUX4) transcription factor skeletal muscle. While epigenetic derepression D4Z4 macrosatellite repeats underlies DUX4 misexpression, our understanding complex transcriptional activation incomplete. To identify potential...
Cryptosporidiosis is a diarrheal disease caused by the parasite Cryptosporidium resulting in over 100,000 deaths annually. Here, we present structure–activity relationship study of benzoic acid position (R6) pyrazolo[3,4-d]pyrimidine lead SLU-2815 (1), an inhibitor phosphodiesterase CpPDE1, discovery benzoxaborole SLU-10906 (63) as bioisostere. Benzoxaborole 63 10-fold more potent than 1 against cell-based infection model (EC50 = 0.19 μM) and non-cytotoxic. Furthermore, has fast rate...
Edwards, John C.; Winkler, Rebecca L.; Bruno, Jonathan M.; Oliva, Author Information