A5012417738- HER2/EGFR in Cancer Research
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- DNA Repair Mechanisms
- Radiation Therapy and Dosimetry
- Carcinogens and Genotoxicity Assessment
- Genomics and Chromatin Dynamics
- RNA and protein synthesis mechanisms
- Effects of Radiation Exposure
- Bacterial Genetics and Biotechnology
- Microtubule and mitosis dynamics
- Radioactivity and Radon Measurements
- CRISPR and Genetic Engineering
- Radioactive contamination and transfer
- Fungal and yeast genetics research
- Genetic factors in colorectal cancer
- Prenatal Screening and Diagnostics
- Bacteriophages and microbial interactions
- Chemical Reactions and Isotopes
- PARP inhibition in cancer therapy
- Bacterial Infections and Vaccines
- Chemical Analysis and Environmental Impact
- Vibrio bacteria research studies
- Peptidase Inhibition and Analysis
- Fish biology, ecology, and behavior
Canadian Nuclear Laboratories
2015-2024
University of Ottawa
2018
Jackson Laboratory
2004-2011
Cornell University
2007-2011
New York State College of Veterinary Medicine
2011
University of British Columbia
1994-2007
University of South Carolina Sumter
2004-2007
University of South Carolina
2007
University of New Brunswick
1997
Abstract A novel mutation, mei8 , was isolated in a forward genetic screen for infertility mutations induced by chemical mutagenesis of ES cells. Homozygous mutant mice are sterile. Mutant females exhibit ovarian dysgenesis and lack follicles at reproductive maturity. Affected males have small testes due to arrest spermatogenesis during meiotic prophase I. Genetic mapping positional cloning led the identification mutation Rec8 homolog yeast meiosis‐specific cohesin gene REC8. Analysis...
The transcriptional regulation of mammalian meiosis is poorly characterized, owing to few genetic and ex vivo models. From a screen, we identify the transcription factor MYBL1 as male-specific master regulator several crucial meiotic processes. Spermatocytes bearing novel separation-of-function allele (Mybl1repro9) had subtle defects in autosome synapsis pachynema, high incidence unsynapsed sex chromosomes, incomplete double-strand break repair on synapsed pachytene chromosomes lack crossing...
DMC1 is a meiosis-specific homolog of bacterial RecA and eukaryotic RAD51 that can catalyze homologous DNA strand invasion D-loop formation in vitro. DMC1-deficient mice yeast are sterile due to defective meiotic recombination chromosome synapsis. The authors identified male dominant allele Dmc1, Dmc1(Mei11), encoding missense mutation the L2 binding domain abolishes activity. Meiosis heterozygotes arrests pachynema, characterized by incomplete synapsis no crossing-over. Young heterozygous...
<p>Supplementary Fig. S5: Chemical structure of trastuzumab-antibody-drug radioconjugate (T-ADR). The naked trastuzumab was first conjugated with the drug linker, then p-SCN-Macropa prior to [<sup>225</sup>Ac]Ac-labeling.</p>
<p>Supplementary Fig. S4: Internalization of immunoconjugates into the lysosomes and endosomes. (A) In HCC1954 JIMT-1 cell lines, rapid time-dependent increase in red fluorescence for trastuzumab respective conjugates was observed from 2 hours (h) to 48 hours. Experiments were done triplicate. (B) Representative phase contrast images with constructs</p>
<p>Supplementary Fig. S1: MALDI-TOF- matrix-assisted laser desorption ionization-time of flight mass spectrometry trastuzumab, T-PEG<sub>6</sub>-DM1, and macropa-T-PEG<sub>6</sub>-DM1 was used to determine the drug-to-antibody ratio (DAR) chelator-to-antibody (CAR) for Macropa.</p>
<p>Supplementary Fig. S7: <i>In vitro</i> stability of [<sup>225</sup>Ac]Ac-Macropa-T-PEG<sub>6</sub>-DM1 and radioligand binding assay. (A) Stability was studied in human serum (HS) PBS for up to 10-d duplicate (n = 2). (B) Saturation assay carried out HER2-positive HCC1954 cell line triplicate 3).</p>
<p>Supplementary Fig. S6: Instant thin layer chromatography (left) and radio-SEC-HPLC (right) of [<sup>225</sup>Ac]Ac-Macropa-T-PEG<sub>6</sub>-DM1. The was obtained by collecting fractions the ADR at different time points running them using gamma counter. results were plotted on excel.</p>
<p>Supplementary Fig. S8: H&E staining of some major organs. Micrographs show no microscopic differences between control (saline) and treatment groups. T: trastuzumab; T-PEG<sub>6</sub>-DM1: trastuzumab-PEG<sub>6</sub>-DM1; [<sup>225</sup>Ac]Ac-T-PEG<sub>6</sub>-DM1 = [<sup>225</sup>Ac]Ac-Macropa-trastuzumab-PEG<sub>6</sub>-DM1.</p>
<p>Supplementary Fig. S3: Sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE) in non-reduced conditions for trastuzumab and its conjugates showing good chemical purity structural integrity of the antibody.</p>
<div>AbstractPurpose:<p>There is overwhelming interest to use actinium-225 ([<sup>225</sup>Ac]Ac) develop targeted α therapies. Antibody–drug conjugates (ADC) are highly cytotoxic. Combining [<sup>225</sup>Ac]Ac with an ADC antibody–drug radioconjugate [<sup>225</sup>Ac]Ac–macropa–trastuzumab(T)–PEG<sub>6</sub>–emtansine (DM1), expected be more effective than its (T–PEG<sub>6</sub>–DM1) against breast...
<p>Supplementary Fig. S2: Size exclusion high performance liquid chromatography (SEC-HPLC) analysis with ultraviolet (uv) detection at 280 nM showing chromatograms of trastuzumab and its conjugates. The confirmed the chemical purity constructs was >95%.</p>
<p>Supplementary Fig. S5: Chemical structure of trastuzumab-antibody-drug radioconjugate (T-ADR). The naked trastuzumab was first conjugated with the drug linker, then p-SCN-Macropa prior to [<sup>225</sup>Ac]Ac-labeling.</p>
<p>Supplementary Fig. S2: Size exclusion high performance liquid chromatography (SEC-HPLC) analysis with ultraviolet (uv) detection at 280 nM showing chromatograms of trastuzumab and its conjugates. The confirmed the chemical purity constructs was >95%.</p>
<p>Supplementary Fig. S7: <i>In vitro</i> stability of [<sup>225</sup>Ac]Ac-Macropa-T-PEG<sub>6</sub>-DM1 and radioligand binding assay. (A) Stability was studied in human serum (HS) PBS for up to 10-d duplicate (n = 2). (B) Saturation assay carried out HER2-positive HCC1954 cell line triplicate 3).</p>
<p>Supplementary Fig. S6: Instant thin layer chromatography (left) and radio-SEC-HPLC (right) of [<sup>225</sup>Ac]Ac-Macropa-T-PEG<sub>6</sub>-DM1. The was obtained by collecting fractions the ADR at different time points running them using gamma counter. results were plotted on excel.</p>
<p>Supplementary Fig. S4: Internalization of immunoconjugates into the lysosomes and endosomes. (A) In HCC1954 JIMT-1 cell lines, rapid time-dependent increase in red fluorescence for trastuzumab respective conjugates was observed from 2 hours (h) to 48 hours. Experiments were done triplicate. (B) Representative phase contrast images with constructs</p>