A5078761451- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Tuberculosis Research and Epidemiology
- Immune Response and Inflammation
- Inflammatory Bowel Disease
- Photochromic and Fluorescence Chemistry
- Nanoplatforms for cancer theranostics
- Advanced biosensing and bioanalysis techniques
- Photodynamic Therapy Research Studies
- Microscopic Colitis
- Carcinogens and Genotoxicity Assessment
- Advanced Chemical Sensor Technologies
- Mycobacterium research and diagnosis
- Gut microbiota and health
- RNA regulation and disease
- Bacterial Infections and Vaccines
- RNA Interference and Gene Delivery
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related molecular mechanisms research
- RNA Research and Splicing
- Adipokines, Inflammation, and Metabolic Diseases
- Atherosclerosis and Cardiovascular Diseases
- Antimicrobial agents and applications
- Biosensors and Analytical Detection
University of Toledo
2022-2025
Massachusetts Institute of Technology
2007-2019
Biological E (India)
2012-2013
Center for Environmental Health
2013
Boston College
2003-2006
Simon Fraser University
2000
University of Utah
2000
Helicobacter hepaticus -infected Rag 2 -/- mice emulate many aspects of human inflammatory bowel disease, including the development colitis and colon cancer. To elucidate mechanisms inflammation-induced carcinogenesis, we undertook a comprehensive analysis histopathology, molecular damage, gene expression changes during disease progression in these mice. Infected developed severe hepatitis by 10 wk post-infection, progressing into carcinoma 20 with pronounced pathology cecum proximal marked...
DNA methylation regulates gene expression in many organisms. In eukaryotes, is associated with repression, while it exerts both activating and repressive effects the Proteobacteria through largely locus-specific mechanisms. Here, we identify a critical methyltransferase M. tuberculosis, which term MamA. MamA creates N6-methyladenine six base pair recognition sequence present approximately 2,000 copies on each strand of genome. Loss reduces number genes. Each has site located at conserved...
Significance Our study investigates chemical damage associated with chronic inflammation and relates these macromolecular products to inflammatory bowel disease activity. Using mice as a model system, we show that responses are common humans produce similar types quantities of in both species. Additional analysis signaling molecules the serum tissue diseased samples highlights role innate immune response overall pathology disease.
The gypsy moth, Lymantria dispar, uses (7R, 8S)-cis-2-methyl-7, 8-epoxyoctadecane, (+)-disparlure, as a sex pheromone. (−) enantiomer of the pheromone is strong behavioral antagonist. Specialized sensory hairs, sensillae, on antennae male moths detect Once enters sensillum, very abundant binding protein (PBP) transports odorant to neuron. We have expressed two PBPs found in moth antennae, PBP1 and PBP2, we studied affinity these recombinant for enantiomers disparlure. To study under...
Oxidative damage to DNA has many origins, including irradiation, inflammation, and oxidative stress, but the chemistries are not same. The most oxidizable base in is 2-deoxyguanosine (dG), primary oxidation products 8-oxodG 2-amino-imidazolone. latter rapidly converts 2,2-diamino-oxazolone (Ox), further oxidized spiroiminodihydantoin (Sp) guanidinohydantoin (Gh). In this study, we have examined dose-response relationship for formation of above four arising calf thymus exposed gamma...
Bacteria respond to environmental stresses using a variety of signaling and gene expression pathways, with translational mechanisms being the least well understood. Here, we identified tRNA methyltransferase in Pseudomonas aeruginosa PA14, trmJ, which confers resistance oxidative stress. Analysis from trmJ mutant revealed that TrmJ catalyzes formation Cm, Um, and, unexpectedly, Am. Defined vitro analyses tRNAMet(CAU) tRNATrp(CCA) are substrates for Cm formation, tRNAGln(UUG), tRNAPro(UGG),...
A renewed interest in non-coding RNA (ncRNA) has led to the discovery of novel species and post-transcriptional ribonucleoside modifications, an emerging appreciation for role ncRNA epigenetics.Although much can be learned by amplification-based analysis sequence quantity, there is a significant need direct RNA, which numerous methods purification specific molecules.However, no single method allows full range cellular species.To this end, we developed multidimensional chromatographic...
Oligosaccharides and glycoconjugates play essential roles in various biological processes such as cellular recognition signaling, thus have attracted tremendous attention the synthetic communities over past few decades. Contributing to this field, we achieved synthesis of aminoxyglycoside pentasaccharide subunit Pseudomonas aeruginosa polysaccharide locus (Psl) exopolysaccharide through an efficient 23 step process. This was designed with aminooxy derivative at reducing end, which used a...
Pseudomonas aeruginosa (PA) is a Gram-negative pathogen that the World Health Organization has ranked as priority 1 (critical) threat. One potential prophylactic approach to preventing or reducing incidence of PA would be development long sought-after vaccine. Both antibody and CD4+ T-cell responses have been noted playing key roles in protection against infection. In these studies, we designed prototype vaccine consisting several known linear B-cell epitopes derived from an outer membrane...
Abstract Upon recognition of a microbial pathogen, the innate and adaptive immune systems are linked to generate cell-mediated response against foreign invader. The culture filtrate Mycobacterium tuberculosis contains ligands, such as M. tRNA, that activate secreted Ags recognized by T cells drive responses. In this study, bioinformatics analysis gene-expression profiles derived from human PBMCs treated with distinct ligands identified mycobacterial tRNA-induced network resulting in robust...
Pseudomonas aeruginosa biofilms can cause chronic infections in burn wounds, grow on medical equipment, and proliferate the lungs of people with cystic fibrosis. These inherently antibiotic tolerant are difficult to eradicate largely due complexity biofilm environment.
The tRNA (m1G37) methyltransferase TrmD catalyzes m1G formation at position 37 in many isoacceptors and is essential most bacteria, which positions it as a target for antibiotic development. In spite of its crucial role, little known about Pseudomonas aeruginosa (PaTrmD), an important human pathogen. Here we present detailed structural, substrate, kinetic properties PaTrmD. mass spectrometric analysis confirmed the G36G37-containing tRNAs Leu(GAG), Leu(CAG), Leu(UAG), Pro(GGG), Pro(UGG),...
Cardiomyopathy is a diabetic comorbidity with few molecular targets. To address this, we evaluated transfer RNA (tRNA) modifications in the heart because tRNA have been implicated etiologies.
A novel class of DNA cleavage agents are reported that derive activity from amino acids tethered to a photoactive intercalator.
Working under oxidative stress: The DNA photocleavage activity of cell-permeable peptide conjugates depends on the nature amino acid side chains present. cellular localization these peptide-based compounds (see fluorescence image a conjugate in living cell) and their phototoxicity were studied human cells, results demonstrate that can be engineered through manipulation sequence composition. Supporting information for this article is available WWW...
Inflammation is now a proven cause of human diseases such as cancer and cardiovascular disease. One potential link between inflammation disease involves secretion reactive chemical species by immune cells, with chronic damage to host epithelial cells leading This suggests pathophysiologically that DNA RNA products are candidate biomarkers inflammation, both for mechanistic understanding the process risk assessment. Of current approaches quantifying products, mass spectrometry-based methods...
One possible mechanism linking inflammation with cancer involves the generation of reactive oxygen, nitrogen, and halogen species by activated macrophages neutrophils infiltrating sites infection or tissue damage, these chemical mediators causing damage that ultimately leads to cell death mutation. To determine most biologically deleterious chemistries inflammation, we previously assessed products across spectrum DNA arising in inflamed tissues SJL mouse model nitric oxide overproduction (...
Benzalkonium chloride (BZK), alkyldimethylbenzlamonium chloride, is a cationic surfactant that used as an antiseptic. BZK classified quaternary ammonium compound composed of molecules several alkyl chains differing lengths, dictate its effectiveness towards different microbes. As result, has become one the most preservatives in antibacterial solutions. Despite widespread use, it not clear whether penetrates human skin. To answer this question, treated skin was analyzed using matrix assisted...
Abstract The properties of a novel family peptide‐based DNA‐cleavage agents are described. Examination the activities systematic series peptide–intercalator conjugates revealed trends that show strong dependence on peptide sequence. Conjugates differing by single residue displayed reactivities varied over wide range. cleavage activity was modulated electrostatic or steric qualities individual amino acids. Isomeric differed in position tether also exhibited different reactivities. mechanism...
Different bacterial cell surface associated biomolecules can be analyzed by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and coupled with collision induced dissociation (CID) for identification. Pseudomonas aeruginosa is an opportunistic, Gram-negative bacterium that causes acute or chronic biofilm infections. Cells of P. communicate through a system signaling known as quorum sensing (QS). The QS result in the production biosurfactant rhamnolipids...
Arbeiten unter oxidativem Stress: Die Aktivität zellpermeabler Peptidkonjugate bei der Photospaltung von DNA hängt den vorhandenen Aminosäureseitenketten ab. Lokalisation dieser peptidbasierten Verbindungen in Zelle (siehe Fluoreszenzbild eines Konjugats einer lebenden Zelle) und ihre Phototoxizität wurden an menschlichen Zellen untersucht; die Ergebnisse belegen, dass über Sequenzfolge eingestellt werden kann. Supporting information for this article is available on the WWW under...
Abstract Inflammatory bowel disease (IBD) is a chronic and relapsing intestinal inflammatory that arises through unknown genetic, environmental, bacterial origins. Ulcerative colitis (UC) Crohn's (CD) are the two main forms of IBD, their incidence increasing in industrialized countries. Further, IBD significant risk factor for development colon cancer. Though specific determinants remain elusive, persistent inflammation believed to play role cancer carcinogenesis. To better define molecular...