- Mass Spectrometry Techniques and Applications
- Analytical Chemistry and Chromatography
- Microfluidic and Capillary Electrophoresis Applications
- DNA and Nucleic Acid Chemistry
- Metabolomics and Mass Spectrometry Studies
- Carcinogens and Genotoxicity Assessment
- DNA Repair Mechanisms
- Molecular Biology Techniques and Applications
- Advanced Chemical Sensor Technologies
- Health, Environment, Cognitive Aging
- Luminescence and Fluorescent Materials
- Ion-surface interactions and analysis
- Molecular Sensors and Ion Detection
- Analytical Chemistry and Sensors
- melanin and skin pigmentation
- Metal complexes synthesis and properties
- Analytical chemistry methods development
- Mast cells and histamine
- Microfluidic and Bio-sensing Technologies
- Effects and risks of endocrine disrupting chemicals
- Electrochemical Analysis and Applications
- Melanoma and MAPK Pathways
- Advanced Chemical Physics Studies
- bioluminescence and chemiluminescence research
- interferon and immune responses
Northeastern University
2014-2024
Institute for Scientific Interchange
2010
University of Turin
2010
Howard Hughes Medical Institute
1997
Harvard University
1997
Formaldehyde is an ubiquitous pollutant to which humans are exposed. Pathologists can experience high formaldehyde exposure levels. Formaldehyde—among other properties—induce oxidative stress and free radicals, react with DNA lipids, leading damage lipid peroxidation, respectively. We measured the levels of air-formaldehyde in a group Italian pathologists controls. analyzed effect on leukocyte malondialdehyde−deoxyguanosine adducts (M1-dG), biomarker peroxidation. studied relationship...
Using a method in which DNA adducts are discovered based on their conversion nucleotide form to phosphorimidazolides with isotopologue benzoylhistamines (or p-bromobenzoylhistamine) prior detection by MALDI-TOF-MS, we have profiled the that when calf thymus is reacted vitro p-benzoquinone (BQ). We find, as relative values normalized 100% of observed, 79% BQ-dCMP, 21% BQ-methyl-dCMP (a new adduct), and trace amounts BQ-dAMP BQ-dGMP. Because mC 5% C this DNA, reaction BQ about five times...
Two derivatives of fluorescein, termed "xanthamides," were prepared from an inexpensive dye. Relative to which contains a 6-phenolic OH and 2'-carboxyl, the first derivative (5) carboxymethyl ether at 6-position secondary amide dimethylamine 2'-position. The second (8) corresponding 6-methyl isonipecotic acid Thus, both contain single carboxyl group, making them monofunctional. Especially 8 is much more photostable (about 10 times) than either fluorescein or BODIPY FL dye when exposed...
A method for nontargeted analysis of modified nucleotides in DNA (and RNA) is reported based on labeling with benzoylhistamine (BH) followed by MALDI-MS. The provides deoxynucleotide-specific detection, accurate measurement molecular ions, high sensitivity, semiquantitation, and, to the extent studied date, normalization response within a factor <3.
N-(2-(Bromomethyl)benzyl)-N,N-diethylethanaminium bromide, that we designate as CAX-B (cationic xylyl-bromide), is presented a derivatization reagent for increasing sensitivity in mass spectrometry. Because of its aryl bromomethyl moiety, readily labels compounds having an active hydrogen. In part, CAX-tagged analyte (CAX-analyte) can be very sensitive especially tandem spectrometer (both ESI and MALDI). This because facile formation analyte-characteristic first product ion (as xylyl-based...
Testing the urine nonpolar sulfateome can enable discovery of xenobiotics that are most likely to be bioactive. This is based on fact more enter cells where they tend undergo metabolism, in part, sulfates then largely excreted into urine.The following sequence steps, with conditions achieve high reproducibility, was applied large human samples: (1) competitive extraction a porous paddle; (2) weak anion-exchange strong organic washing; and (3) ultrahigh-performance liquid chromatography...
We investigate the limit of detection for obtaining NMR data a DNA adduct using modern microscale instrumentation, once has been isolated at picomole level. Eighty nanograms (130 pmol) standard, N-(2'-deoxyguanosin-8-yl)-2-acetylaminofluorene 5'-monophosphate (AAF-dGMP), in 1.5 μL D₂O with 10% methanol-d₄, vial, was completely picked up as droplet suspended fluorocarbon liquid and loaded efficiently into microcoil probe. This work demonstrates practical manual method microfluidic sample...
Rationale As a new approach to DNA adductomics, we directly reacted intact, double‐stranded (ds)‐DNA under warm conditions with an alkylating mass tag followed by analysis liquid chromatography/mass spectrometry. This method is based on the tendency of adducted nucleobases locally disrupt structure (forming “DNA bubble”) potentially increasing exposure their nucleophilic (including active hydrogen) sites for preferential alkylation. Also encouraging this strategy that scope nucleotide...
While MALDI-MS of intact genomic DNA is unheard of, actually many adducts can be detected in this way under certain MALDI conditions: relatively high molar ratio nucleobases to matrix (0.01 0.3), hot (CCA), and laser fluence. This because create "bubbles" on dsDNA (disruption base pairing), making it easier for these as modified jettisoned by the laser-derived energy (jettison mass spectrometry or JeMS). The method also works other nucleic acid species, namely nucleobases, nucleosides,...
Phenols are an important class of analytes, for example as bioactive environmental contaminants. Towards a goal improving their detection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) or MALDI-tandem (TOF/TOF)-MS, we studied derivatization with 2-sulfobenzoic anhydride (SBA). We chose SBA this purpose since it is commercially available, inexpensive, and forms anionic derivative.Under the selected conditions developed here phenols, reaction...
Toward a goal of dideoxy sequencing DNA utilizing electrophore labels, we prepared four electrophore-labeled oligonucleotide primers. Each primer has different and sequence but common glycol keto (α,β-dihydroxyketo) release group. Cleavage this latter group by either periodate oxidation or thermal retroaldol reaction releases the electrophores for detection mass spectrometry. Successful data with these primers was obtained capillary electrophoresis on an ABI Model 310 after fluorescence...
Microphthalmia-associated transcription factor (MITF) plays pivotal roles in melanocyte development, function, and melanoma pathogenesis. MITF amplification occurs has been associated with resistance to targeted therapies. Here, we show that regulates a global antioxidant program increases survival of cell lines by protecting the cells from reactive oxygen species (ROS)-induced damage. In addition, this redox is correlated expression human patient-derived samples. Using zebrafish model,...
The four major deoxynucleotides of DNA, and adduct mixtures resulting from separate reactions 5'-dAMP 5'-dGMP with benzo[a]pyrene diolepoxide (BPDE), were analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) after labeling their phosphate group an IMI dye. latter reagent comprises imidazole functional attached to a BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene+ ++) fluorophore. Good sensitivity was observed in the detection IMI-labeled...
Two techniques are reported for detection of electrophorederivatized compounds by laser-induced electron capture time-of-flight mass spectrometry (LI-EC-TOF-MS). In both cases, a nitrogen laser is used to induce the capture. The analyte deposited in matrix consisting compound with low ionization potential such as benzo[ghi]perylene first technique, where apparently comes from this matrix. second on silver surface absence It seems that "monoenergetic" ions instantly desorb target latter case,...
Background: For MM and AL patients undergoing AHCT, high-dose melphalan is given at a fixed dose based on body surface area with five-fold inter-patient variability in exposure by under the curve (AUC). Pts higher than median AUC have prolonged survival, but increased toxicity (Shaw et al., BBMT 2012). Pharmacokinetic (PK)-directed dosing can determine optimal concentration for each pt. We prospectively evaluated feasibility of PK-directed PGF-MEL, more stable possibly less toxic intravenous...
Albumin was reacted with a mixture of six electrophore N-hydroxysuccinimide esters, each which possessed an interior glycolketo linkage. The purpose this linkage is to release the attached as ketone when heated, due thermal retro-aldol reaction. multiplex electrophore-labeled albumin detected dried spot deposited on polyimide membrane by laser desorption/capillary collection (of released electrophores)/off-line gas chromatography/electron caputre-mass spectrometry. This encourages further...