A5010111304- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- Bacterial Genetics and Biotechnology
- CRISPR and Genetic Engineering
- Cancer-related gene regulation
- Enzyme Structure and Function
- Protein Kinase Regulation and GTPase Signaling
- Signaling Pathways in Disease
- Protein Structure and Dynamics
- Genomics and Chromatin Dynamics
- Mycobacterium research and diagnosis
- Cancer, Hypoxia, and Metabolism
- Mass Spectrometry Techniques and Applications
- Glycosylation and Glycoproteins Research
- Melanoma and MAPK Pathways
- Peroxisome Proliferator-Activated Receptors
- Hemoglobinopathies and Related Disorders
- Lipid metabolism and biosynthesis
- 14-3-3 protein interactions
- Amino Acid Enzymes and Metabolism
- Cell death mechanisms and regulation
- Biochemical and Molecular Research
The University of Texas MD Anderson Cancer Center
2018-2024
Scripps MD Anderson Cancer Center
2022
Institute for Applied Science
2022
Rice University
2013-2016
University of North Carolina at Chapel Hill
2002-2014
Hauptman-Woodward Medical Research Institute
2012-2014
University at Buffalo, State University of New York
2012-2014
Woodward (United States)
2012
Institute of Molecular Biology and Biophysics
2006
UNC Lineberger Comprehensive Cancer Center
2005
An emerging molecular understanding of RNA alkylation and its removal is transforming our knowledge biology interplay with cancer chemotherapy responses. DNA modifications are known to perform critical functions depending on the genome template, including gene expression, replication timing, damage protection, yet current results suggest that chemical diversity pales in comparison those RNA. More than 150 have been identified date, their complete functional implications still being unveiled....
Mechanistic studies in DNA repair have focused on roles of multi-protein complexes, so how long non-coding RNAs (lncRNAs) regulate is less well understood. Yet, lncRNA LINP1 over-expressed multiple cancers and confers resistance to ionizing radiation chemotherapeutic drugs. Here, we unveil structural mechanistic insights into LINP1's ability facilitate non-homologous end joining (NHEJ). We characterized structure flexibility analyzed interactions with the NHEJ factor Ku70/Ku80 (Ku) Ku...
Hydrogen-deuterium exchange (HDX) combined with mass spectrometry (MS) is a powerful technique for studying changes in protein structure and dynamics upon ligand binding. Protein-ligand complexes can result increased protection of peptide-bond amides HDX indicating stabilization. We have characterized the interaction lead inhibitor candidates towards KRas G12D oncoprotein by intact bottom-up HDX-MS combination molecular (MD) simulations. Significant differences were detected binding flexible...
An important step in screening small molecule libraries for drug discovery is hit prioritization and validation to rule out false positives, which usually performed using biochemical biophysical assays. The development of orthogonal assays that are highly sensitive can accelerate the hit-to-lead process valuable. Limited proteolysis combined with mass spectrometry (LiP-MS) a technique used study changes protein structure upon ligand binding. In LiP-MS, proteins exposed low concentrations...
Histone mRNAs are rapidly degraded at the end of S phase, and a 26-nucleotide stem-loop in 3' untranslated region is key determinant histone mRNA stability. This sequence binding site for protein (SLBP), which helps to recruit components RNA degradation machinery end. SLBP only whose expression cell cycle regulated during phase temporally correlated with degradation. Here we report that chemical inhibition prolyl isomerase Pin1 or downregulation by small interfering (siRNA) increases...
Activating signal co-integrator complex 1 (ASCC1) acts with ASCC-ALKBH3 in alkylation damage responses. ASCC1 uniquely combines two evolutionarily ancient domains: nucleotide-binding K-Homology (KH) (associated regulating splicing, transcriptional, and translation) two-histidine phosphodiesterase (PDE) hydrolysis of cyclic nucleotide phosphate bonds). Germline mutations link loss function to spinal muscular atrophy congenital bone fractures 2 (SMABF2). Herein analysis The Cancer Genome Atlas...
The stem–loop-binding protein (SLBP) is involved in multiple aspects of histone mRNA metabolism. To characterize the modification status and sites SLBP, we combined mass spectrometric bottom-up (analysis peptides) top-down intact proteins) proteomic approaches. Drosophilia SLBP heavily phosphorylated, containing up to seven phosphoryl groups. Accurate M r determination by Fourier transform ion cyclotron resonance (FTICR)-MS FTICR-MS experiments using a variety dissociation techniques show...
Abstract The Anfinsen hypothesis, the demonstration of which led to Nobel prize in Chemistry, posits that all information required determine a proteins’ three dimensional structure is contained within its amino acid sequence. This suggests it should be possible, theory, fold any protein vitro . In practice, however, production by refolding challenging because suitable conditions must empirically determined for each and can painstaking. Here we demonstrate, using variety proteins,...
Vav proteins are Rho GTPase-specific guanine nucleotide exchange factors (GEFs) that distinguished by the tandem arrangement of Dbl homology (DH), Pleckstrin (PH), and cysteine rich domains (CRD). Whereas DH−PH is conserved among GEFs, presence CRD unique to family members required for efficient exchange. We provide evidence Vav2-mediated GTPases follows Theorell−Chance mechanism in which Vav2·Rho GTPase complex major species during process Vav2·GDP-Mg2+·Rho ternary present only transiently....
Phosphopeptides can be difficult to detect and sequence by mass spectrometry (MS) due low ionization efficiency suppression effects in the MS mode, insufficient fragmentation tandem (MS/MS) respectively. To address this problem, we have developed a technique called Phosphatase-directed Phosphorylation-site Determination (PPD), which combines on-target phosphatase reactions, MALDI MS/MS of IMAC beads on target, hypothesis-driven (HD−MS). In method, dephosphorylation experiments are conducted...
In metazoans, the majority of histone proteins are generated from replication-dependent mRNAs. These mRNAs unique in that they not polyadenylated but have a stem-loop structure their 3' untranslated region. An early event end formation is binding protein (SLBP) to structure. Here we provide insight into mechanism by which SLBP contacts mRNA. There two sites RNA domain for mRNA hairpin. The first site (Glu129-Val158) consists helix-turn-helix motif likely recognizes unpaired uridines loop...
Cancer is a metabolic disease. cells, being highly proliferative, show significant alterations in pathways such as glycolysis, respiration, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, lipid metabolism, and amino metabolism. Metabolites like peptides, nucleotides, products of TCA fatty acids, steroids can be an important read out disease when characterized biological samples tissues body fluids urine, serum, etc. The cancer metabolome has been studied since 1960s by...
The peptidyl-prolyl isomerase Pin1 is over-expressed in several cancer tissues a potential prognostic marker prostate cancer, and ablation can suppress tumorigenesis breast cancers. co-operate with activated ErbB2 or Ras to enhance tumorigenesis. It does so by regulating the activity of proteins that are essential for gene expression cell proliferation. Several targets such as c-Myc, Androgen Receptor, Estrogen Receptor-alpha, Cyclin D1, E, p53, RAF kinase NCOA3 deregulated cancer. At...
The DnaQ-H family exonuclease Snipper (Snp) is a 33-kDa Drosophila melanogaster homolog of 3′hExo and ERI-1, exoribonucleases implicated in the degradation histone mRNA mammals negative regulation RNA interference (RNAi) Caenorhabditis elegans , respectively. In metazoans, Snp, Exod1, 3′hExo, prpip nucleases define new subclass structure-specific 3′-5′ exonucleases that bind degrade double-stranded and/or DNA substrates with 3′ overhangs 2–5 nucleotides (nt) presence Mg 2+ no apparent...
A 13 amino acid insertion that forms a short 310 helix between β-strand 5 and α-helix 4 is distinguishing feature among most members of the Rho family GTPases, yet precise role this region in signal transduction poorly understood. Previous vivo functional studies have implicated insert RhoA, Rac1, Cdc42 to be important for cell transformation, regulation actin cytoskeleton, controlling DNA synthesis, activation downstream targets. In our recent biological suggested SRF formation lamellipodia...