A5101915515- RNA modifications and cancer
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Multiple Myeloma Research and Treatments
- Cancer-related gene regulation
- Protein Degradation and Inhibitors
- Amino Acid Enzymes and Metabolism
- Silymarin and Mushroom Poisoning
- Lymphoma Diagnosis and Treatment
- DNA Repair Mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Ubiquitin and proteasome pathways
- Toxin Mechanisms and Immunotoxins
- Genomics and Phylogenetic Studies
- Chemical Synthesis and Analysis
- Fibroblast Growth Factor Research
- Circular RNAs in diseases
- Biopolymer Synthesis and Applications
- Immunotherapy and Immune Responses
- Medicinal Plant Pharmacodynamics Research
- Renal Diseases and Glomerulopathies
- Biomarkers in Disease Mechanisms
- Genomics and Chromatin Dynamics
- Monoclonal and Polyclonal Antibodies Research
The University of Texas MD Anderson Cancer Center
2018-2024
The University of Texas Health Science Center at Houston
2022
Emory University
2010-2020
California State University, Fullerton
2017
Wayne State University
2012
The mammalian thymine DNA glycosylase (TDG) is implicated in active demethylation via the base excision repair pathway. TDG excises mismatched from G:X mismatches, where X uracil, or 5-hydroxymethyluracil (5hmU). These are, respectively, deamination products of cytosine, 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). In addition, Tet protein 5-formylcytosine (5fC) 5-carboxylcytosine (5caC) but not 5hmC 5mC, when paired with a guanine. Here we present post-reactive complex...
Background A devastating late injury caused by radiation is pulmonary fibrosis. This risk may limit the volume of irradiation and compromise potentially curative therapy. Therefore, development a therapy to prevent this toxicity can be great benefit for patient population. Activation chemokine receptor CXCR4 its ligand stromal cell-derived factor 1 (SDF-1/CXCL12) important in radiation-induced Here, we tested whether MSX-122, novel small molecule partial antagonist, block fibrotic process....
KRAS, NRAS, and BRAF mutations which activate p44/42 mitogen-activated protein kinase (MAPK) signaling are found in half of myeloma patients contribute to proteasome inhibitor (PI) resistance, but the underlying mechanisms not fully understood. We established cell lines expressing wild-type (WT), constitutively active (CA) (G12V/G13D/Q61H), or dominant-negative (DN) (S17N)-KRAS -NRAS, BRAF-V600E. Cells CA mutants showed increased maturation (POMP) nuclear factor (erythroid-derived 2)-like 2...
Significance Accurate gene expression is essential in all organisms. During protein synthesis, transfer RNAs (tRNAs) decode the genetic information contained messenger RNA (mRNA) on ribosome into amino acids using a defined 3-nt code. A fundamental question biology how maintains this code, or mRNA frame, during dynamic processes that move mRNA-tRNA pairs through different tRNA-binding sites. We solved structures of frameshift-prone tRNA bound to bacterial after decoding. find undergoes...
Activator protein 1 (AP-1) is a transcription factor that recognizes two versions of 7-base pair response element, either 5΄- GAG CA-3΄ or (where M = 5-methylcytosine). These elements share the feature 5-methylcytosine and thymine both have methyl group in same position, 5-carbon pyrimidine, so each them has groups at nucleotide positions 5 from 5΄ end, resulting four symmetrically positioned duplex DNA. Epstein-Barr Virus Zta key transcriptional regulator viral lytic cycle homologous to...
Modifications in the tRNA anticodon loop, adjacent to three-nucleotide anticodon, influence translation fidelity by stabilizing allow for accurate reading of mRNA genetic code. One example is N1-methylguanosine modification at guanine nucleotide 37 (m 1 G37) located loop andimmediately nucleotides 34, 35, 36. The absence m G37 Pro causes +1 frameshifting on polynucleotide, slippery codons. Here, we report structures bacterial ribosome containing bound either cognate or codons determine how...
Abstract Inflammatory processes play a key role in pathophysiology of many neurologic diseases/trauma, but the effect immune cells and factors on neurotransplantation strategies remains unclear. We hypothesized that cellular humoral components innate immunity alter fate migration human neural stem (hNSC). In these experiments, conditioned media collected from polymorphonuclear leukocytes (PMN) selectively increased hNSC astrogliogenesis promoted cell vitro. PMN were shown to generate C1q...
Highlights•Cryo-EM structures of the 70S bound to an mRNA stem loop reveal interactions with uS3•E-site tRNA shows a unique conformation in presence loop•E-site forms 30S head domain•Structured mRNAs regulate tRNAs affect translationSummaryStructured positioned downstream ribosomal decoding center alter gene expression by slowing protein synthesis. Here, we solved cryo-EM structure bacterial ribosome containing 3′ that regulates translation. Unexpectedly, E-site adopts two distinct...
Glioblastoma is the most common primary brain tumor and uniformly fatal despite aggressive surgical adjuvant therapy. As survival short, it critical to determine value of therapy early on in treatment. Improved predictive assessment would allow neuro‐oncologists personalize adjust or change treatment sooner maximize use efficacious During carcinogenesis, suppressor genes can be silenced by aberrant histone deacetylation. This epigenetic modification has become an important target for...
Abstract The interaction of CXCR4 with CXCL12 (SDF‐1) plays a critical role in cancer metastasis by facilitating the homing tumor cells to metastatic sites. Based on our previously published work antagonists, we have synthesized series aryl sulfonamides that inhibit CXCR4/CXCL12 interaction. Analogue bioactivities were assessed binding affinity and Matrigel invasion assays. Computer modeling was employed evaluate selection new analogues docked into X‐ray structure rationalize discrepancies...
Abstract B-cell maturation antigen (BCMA) plays a pathobiologic role in myeloma and is validated target with five BCMA-specific therapeutics having been approved for relapsed/refractory disease. However, these drugs are not curative, responses inferior patients molecularly-defined high-risk disease, including those deletion 17p (del17p) involving the tumor suppressor TP53 , supporting need further drug development. Del17p has associated reduced copy number gene expression of RNA polymerase...
Abstract Background Interleukin 4 (IL-4), increased in tuberculosis infection, may impair bacterial killing. Blocking IL-4 confers benefit animal models. We evaluated safety and efficacy of pascolizumab (humanized anti–IL-4 monoclonal antibody) as adjunctive treatment. Methods Participants with rifampicin-susceptible pulmonary received a single intravenous infusion or placebo, standard 6-month Pascolizumab dose successive cohorts: (1) nonrandomized 0.05 mg/kg (n = 4); (2) 0.5 (3) randomized...
ABSTRACT Modifications in the tRNA anticodon, adjacent to three-nucleotide influence translation fidelity by stabilizing allow for accurate reading of mRNA genetic code. One example is N1-methylguaonosine modification at guanine nucleotide 37 (m 1 G37) located anticodon loop, immediately nucleotides 34-36. The absence m G37 Pro causes +1 frameshifting on polynucleotide, slippery codons. Here, we report structures bacterial ribosome containing bound either cognate or codons determine how...
Ribosome dysregulation is the underlying cause for multiple disease states and primary mechanism by which many bacterial antibiotics function.My laboratory currently studies three aspects of translation regulation: mRNA frame maintenance fidelity protein synthesis, cell stress toxin-mediated decay, antibiotic resistance mediated RNA modifications.Since ribosome one critical cellular macromolecular complexes numerous are attributed to mutations in factors, tRNAs or mRNAs, understanding...
Abstract DNA methylation is generally known to inhibit transcription factor binding. However, this notion has been challenged with identifications of several factors that preferentially activate methylated promoters in specific sequences. AP-1 (c-Jun/c-Fos heterodimer), a master regulator wide range cancer-related genes, shown bind novel consensus sequence (5'-TGACTCG-3') CpG methylation-dependent manner. In the fluorescence polarization-based binding assay, both c-Jun/c-Fos heterodimer and...
During the development, mammalian germ line cells and brains undergo a series of cellular molecular events that lead to erasure re-establishment epigenetic programs. It is possible active 5-methylcytosine (5mC) marks during differentiation brain development from fetus young adult involve dynamic changes 5mC into oxidative marks, these modified cytosine residues in DNA are recognized by specific protein readers with distinct roles maintenance memory. Here we report our on-going biochemical...