A5036003228- Antimicrobial Peptides and Activities
- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Fungal and yeast genetics research
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Heparin-Induced Thrombocytopenia and Thrombosis
- Pancreatic function and diabetes
- Adenosine and Purinergic Signaling
- CAR-T cell therapy research
- Neuropeptides and Animal Physiology
- Pediatric health and respiratory diseases
- Biochemical and Structural Characterization
- Mast cells and histamine
- Malaria Research and Control
- Pneumocystis jirovecii pneumonia detection and treatment
- Neurological diseases and metabolism
- Cholesterol and Lipid Metabolism
- Blood Coagulation and Thrombosis Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Intramuscular injections and effects
- Neuroscience and Neuropharmacology Research
- Carbohydrate Chemistry and Synthesis
- RNA regulation and disease
- Lipid Membrane Structure and Behavior
Fox Chase Chemical Diversity Center
2014-2023
Poly Med (United States)
2012-2014
Fox Chase Cancer Center
2014
GlaxoSmithKline (United States)
2003-2007
Providence College
2005
GlaxoSmithKline (United Kingdom)
2001
New Frontier
1996-2000
Columbia University
1996
Brown University
1995
Hasbro Children's Hospital
1995
The amyloidogenic pathway leading to the production and deposition of Abeta peptides, major constituents Alzheimer disease senile plaques, is linked neuronal metal homeostasis. amyloid precursor protein binds copper zinc in its extracellular domain, peptides also bind copper, zinc, iron. first step generation cleavage by aspartic protease BACE1. Here we show that BACE1 interacts with CCS (the chaperone for superoxide dismutase-1 (SOD1)) through domain I proteins co-immunoprecipitate from rat...
Rap1p is a transcriptional regulator of Saccharomyces cerevisiae, which plays roles in both activation and silencing. To identify proteins involved Rap1p-dependent regulation transcription, we used the two-hybrid system to screen for Rap1p-interacting proteins. Two clones isolated from this encode truncated protein with homology small heat shock (HSPs). Here present an analysis novel S. cerevisiae HSP, name Hsp42p. Expression HSP42 regulated by range stress conditions similar HSP26, Hsp42p...
A series of self-associating foldamers have been designed as heparin reversal agents, antidotes to prevent bleeding due this potent antithrombotic agent. The a repeating sequence Lys-Sal, in which Sal is 5-amino-2-methoxy-benzoic acid. These are self-associate along one face an extended chain β-sheet-like interaction. methoxy groups were included form intramolecular hydrogen bonds that preclude the formation very large amyloid-like aggregates, while positively charged Lys side chains...
Lethal systemic fungal infections of Candida species are increasingly common, especially in immune compromised patients. By vitro screening small molecule mimics naturally occurring host defense peptides (HDP), we have identified several active antifungal molecules, which also exhibited potent activity two mouse models oral candidiasis. Here show that one such compound, C4, exhibits a mechanism action is similar to the parent HDP upon it was designed. Specifically, its initial interaction...
GABA(B) receptors are heterodimeric G protein-coupled that mediate slow synaptic inhibition in the central nervous system. Whereas heterodimerization between receptor GABA(B)R1 and GABA(B)R2 subunits is essential for functional expression, how neurons coordinate assembly of these critical remains to be established. Here we have identified Marlin-1, a novel receptor-binding protein associates specifically with subunit yeast, tissue culture cells, neurons. Marlin-1 expressed brain exhibits...
ABSTRACT There is a strong need for new broadly active antifungal agents the treatment of oral candidiasis that not only are against many species Candida , including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide foundation development such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics HDPs improve safety and other pharmaceutical properties. Here describe...
Host-defense peptides (HDPs) have an important therapeutic potential against microbial infections but their metabolic instability and cellular cytotoxicity limited utility. To overcome these limitations, we utilized five small-molecule, nonpeptide HDP mimetics (smHDPMs) tested effects on cytotoxicity, antimicrobial activity, mast cell (MC) degranulation. None of the smHDPMs displayed mouse 3T3 fibroblasts or human transformed liver HepG2 cells. However, one compound had both antifungal...
Invasive candidiasis caused by Candida albicans and non-albicans (NAC) present a serious disease threat. Although the echinocandins are recommended as first line of antifungal drug class, resistance to these agents is beginning emerge, demonstrating need for new agents. Host defense peptides (HDP) exhibit potent activity, but drugs they difficult manufacture efficiently, often inactivated serum proteins. HDP mimetics low molecular weight non-peptide compounds that can alleviate problems were...
The promoters of the Saccharomyces cerevisiae histone H3 and H4 genes were examined for cis-acting DNA sequence elements regulating transcription cell division cycle control. Deletion linker disruption mutations identified two classes regulatory elements: multiple activation (CCA) sites a negative site (NRS). Duplicate 19-bp CCA are present in both copy I II H3-H4 arranged as inverted repeats separated by 45 68 bp. necessary sufficient to activate under A single provides control but is weak...
Previous work done by our laboratory described the use of an immunocompetent spontaneous melanoma-prone mouse model, TGS (TG-3/SKH-1), to evaluate treatment outcomes using inhibitors glutamatergic signaling and immune checkpoint for 18 weeks. We showed a significant therapeutic efficacy with notable sex-biased response in male mice. In this follow-up 18-week study, dose inhibitor was increased (from 1.7 mg/kg 25 mg/kg), which resulted improved responses female mice but not The greatest...
Disseminated infection by
Systemic fungal infections are increasingly common, especially in immune compromised patients. Even with newly developed drugs, there remain issues of limited spectrum, side effects, and the development resistance. Host defense peptides (HDPs) have been examined recently for their utility as therapeutic antifungals, due to low levels resistance that develop. Unfortunately, exhibit poor pharmacologic properties vivo. We demonstrated potent activity nonpeptidic compounds mimic HDPs both...