A5079817220- Acute Myeloid Leukemia Research
- Zebrafish Biomedical Research Applications
- Mass Spectrometry Techniques and Applications
- Erythrocyte Function and Pathophysiology
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Analytical Chemistry and Chromatography
- Autophagy in Disease and Therapy
- Sperm and Testicular Function
- DNA Repair Mechanisms
- Pesticide Exposure and Toxicity
- Hematopoietic Stem Cell Transplantation
- Cancer, Hypoxia, and Metabolism
- Selenium in Biological Systems
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Environmental Toxicology and Ecotoxicology
- PARP inhibition in cancer therapy
- Genomics and Chromatin Dynamics
- Effects and risks of endocrine disrupting chemicals
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Ion-surface interactions and analysis
- Cancer Genomics and Diagnostics
Pennsylvania State University
2024-2025
Baylor College of Medicine
2018-2025
Penn State Milton S. Hershey Medical Center
2024
University of Hong Kong
2013-2020
GlaxoSmithKline (United States)
2017
Chinese University of Hong Kong
2013-2014
Aileron (United States)
2013
Reproductive Medicine Institute
2011
State Key Laboratory of Reproductive Medicine
2011
Nanjing Medical University
2010-2011
Significance Stapled α−helical peptides have emerged as a promising new modality for wide range of therapeutic targets. Here, we describe the development stapled peptide lead molecule treatment cancers that possess intact p53 tumor suppressor protein but are resistant to drug therapy because overexpression inhibitory proteins MDM2 and MDMX. The ATSP-7041 is highly potent dual inhibitor both MDMX shown effectively reactivate pathway in mechanism-dependent manner p53-positive vitro vivo.
A DNA-encoded macrocyclic peptide library was designed and synthesized with 2.4 × 1012 members composed of 4-20 natural non-natural amino acids. Affinity-based selection performed against two therapeutic targets, VHL RSV N protein. On the basis data, some peptides were selected for resynthesis without a DNA tag, their activity confirmed.
Targeting the dependency of MLL-rearranged (MLLr) leukemias on menin with small molecule inhibitors has opened new therapeutic strategies for these poor-prognosis diseases. However, rapid development inhibitor resistance calls combinatory to improve responses and prevent resistance. Here we show that leukemia stem cells (LSCs) MLLr acute myeloid (AML) exhibit enhanced guanine nucleotide biosynthesis, inhibition which leads differentiation sensitization inhibitors. Mechanistically, targeting...
Nuclear NAD + homeostasis governed by NMNAT1 prevents apoptosis in AML stem cells suppressing p53.
Human telomeric repeat binding factor 2 (hTRF2) is a protein that plays an important role in capping human telomeres to protect them from DNA damage repair systems. The ineffectiveness of hTRF2 may be linked aging and cancer. We report the use PLIMSTEX (protein−ligand interactions by mass spectrometry, titration, H/D exchange) selective acetylation lysine residues study interaction DNA-binding domain double-stranded (repeats TTAGGG). By increasing resolution peptide level, we localized...
Background Nucleotide excision repair (NER) and base (BER) are the primary mechanisms for of bulky adducts caused by chemical agents, such as PAHs. It is expected that polymorphisms in NER or BER genes may modulate individual susceptibility to PAHs exposure. Here, we evaluate effects exposure pathway, alone combined, on polycyclic aromatic hydrocarbon-DNA (PAH–DNA) human sperm. Methodology/Principal Findings Sperm PAH-DNA were measured immunofluorescent assay using flow cytometry a sample...
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of variety environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs) and dioxins. We hypothesized polymorphisms AHR may result in significant differences sensitivity to toxic effects PAHs or dioxins contribute susceptibility male infertility. To address this possibility, we conducted study including 580 idiopathic infertile subjects fertile controls assess associations...
Time-resolved measurements were conducted to relate the fluorescence lifetimes of dye-derivatized polypeptides local conformational dynamics in trapped, unsolvated peptide ions. This research was performed better understand intramolecular interactions leading observed increase quenching with temperature and, particular, how this is related fluctuations. Dye-derivatized polyproline ions, Dye-[Pro] n -Arg (+)-Trp, are formed by electrospray ionization and trapped a variable-temperature...
Peptide drugs have traditionally suffered from poor pharmacokinetic properties due to their conformational flexibility and the interaction of proteases with backbone amide bonds. "Stapled Peptides" are cyclized using an all-hydrocarbon cross-linking strategy reinforce α-helical conformation, yielding improved protease resistance drug-like properties. Here we demonstrate that hydrogen exchange-mass spectrometry (HX-MS) effectively probes dynamics Stapled Peptides derived survivin-borealin...
Histone variants contribute to the complexity of chromatin landscape and play an integral role in defining DNA domains regulating gene expression. The histone H3 variant H3.3 is incorporated into genic elements independent replication by its chaperone HIRA. Here we demonstrate that Hira required for self-renewal adult hematopoietic stem cells (HSCs) restrain erythroid differentiation. Deletion led rapid depletion HSCs while differentiated remained largely unaffected. Depletion after deletion...
Methods have been developed to measure the fluorescence lifetime versus temperature of trapped biomolecular ions derivatized with a fluorescent dye. Previous measurements for different sequences polyproline peptides demonstrated that quenching rates are related conformations and their spatial fluctuations. This paper presents results extending these methods study conformational dynamics larger biomolecules. Vancomycin-peptide noncovalent complexes in 1+ charge state were studied as function...
Abstract Laser spray, which is a newly developed ionization technique, can characterize the stability of noncovalent complexes in solution phase. By using this advantage, laser spray has been applied to probe intrinsic double‐stranded DNA (dsDNA) sequences and their binding affinities with various drugs Systematic experiments were carried out six 16‐mer three 22‐mer dsDNA oligomers, together minor groove binders: berenil, Hoechst 33342, DAPI, netropsin. Dissociation curves for each or...
Abstract The stability and conformational changes of cytochrome c (cyt c) at different temperatures pH have been well examined so far by using various analytical methods. We found that laser spray mass spectrometry enables much faster more convenient monitoring those cyt compared with other results correlated circular dichroism (CD) experiments under relatively acidic conditions, which destabilize the protein. Laser spectra were obtained levels power. Bimodal charge‐state distributions...