A5009896247- Cancer Research and Treatments
- Metal-Catalyzed Oxygenation Mechanisms
- Amino Acid Enzymes and Metabolism
- RNA modifications and cancer
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- RNA regulation and disease
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Telomeres, Telomerase, and Senescence
- Enzyme Structure and Function
- Genetics, Aging, and Longevity in Model Organisms
- Cytomegalovirus and herpesvirus research
- Genomics and Chromatin Dynamics
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Biosimilars and Bioanalytical Methods
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Transgenic Plants and Applications
- Trace Elements in Health
St. Jude Children's Research Hospital
2024-2025
Agency for Science, Technology and Research
2018-2024
Institute of Molecular and Cell Biology
2022-2024
Genome Institute of Singapore
2018-2019
Nanyang Technological University
2017-2018
University of Stuttgart
2014-2015
Constructor University
2012
While CRISPR-Cas systems hold tremendous potential for engineering the human genome, it is unclear how well each system performs against one another in both non-homologous end joining (NHEJ)-mediated and homology-directed repair (HDR)-mediated genome editing.
Abstract The Dnmt2 RNA methyltransferase catalyses the methylation of C38 in anticodon loop tRNA-Asp, but molecular role this is unknown. Here, we report that mouse aspartyl-tRNA synthetase shows a four to fivefold preference for C38-methylated tRNA-Asp. Consistently, 30% reduced charging level tRNA-Asp was observed knockout (KO) murine embryonic fibroblast cells. Gene expression analysis with fluorescent reporter proteins fused an N-terminal poly-Asp sequence showed protein synthesis...
Abstract Mammalian host cell lines are the preferred expression systems for manufacture of complex therapeutics and recombinant proteins. However, most utilized mammalian systems, namely Chinese hamster ovary (CHO), Sp2/0 NS0 mouse myeloma cells, can produce glycoproteins with non-human glycans that may potentially illicit immunogenic responses. Hence, we developed a fully human system based on HEK293 cells stable high titer production proteins by first knocking out GLUL (encoding glutamine...
Over-consumption of iron-rich red meat and hereditary or genetic iron overload are associated with increased risk colorectal carcinogenesis, yet the mechanistic basis how metal-mediated signaling leads to oncogenesis remains enigmatic. Using fresh cancer (CRC) samples we identify Pirin, an sensor, that overcomes a rate-limiting step in oncogenesis, by re-activating dormant human-reverse-transcriptase (hTERT) subunit telomerase holoenzyme iron-(Fe3+)-dependent-manner thereby drives CRCs....
Background Oncofetal splice variants of extracellular matrix (ECM) proteins present a unique group target antigens for the immunotherapy pediatric cancers. However, limited data is available if these can be targeted with T cells expressing chimeric antigen receptors (CARs). Methods To determine expression oncofetal version tenascin C (TNC) encoding domain (C.TNC) in brain and solid tumors, we used quantitative reverse transcription PCR immunohistochemistry. Genetically modified were...
Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is the expansion a hematopoietic stem cell clone with an acquired leukemia-associated mutation in individuals without any evident hematological disease. CHIP age-related phenomenon associated increased risk death from cardiovascular disease or hematologic malignancy. Mutations DNA Methyltransferase 3a (DNMT3A) are present >50% age-associated CHIP. In setting allogeneic bone marrow transplantation, clones transmitted 20%...
Dnmt2 enzymes are conserved in eukaryotes, where they methylate C38 of tRNA-Asp with high activity. Here, the activity one very few prokaryotic homologs from Geobacter species (GsDnmt2) was investigated. GsDnmt2 observed to flies and mice. Unexpectedly, it had only a weak toward its matching tRNA-Asp, but methylated tRNA-Glu good In agreement this result, we show that is while methylation absent tRNA-Asp. The activities Homo sapiens, Drosophila melanogaster, Schizosaccharomyces pombe...
Adenosine-to-inosine (A-to-I) RNA editing displays diverse spatial patterns across different tissues. However, the human genome encodes only two catalytically active enzymes (ADAR1 and ADAR2), suggesting that other regulatory factors help shape landscape. Here, we show splicing factor SRSF9 selectively controls of many brain-specific sites in primates. is more lowly expressed brain than non-brain Gene perturbation experiments minigene analysis candidate demonstrated could robustly repress...
Significance Mutations in hTERT promoter are seen over 19% of human cancers, irrespective the cancer type. Understanding molecular players that regulate Mut- promoters may help design effective targeting strategies to inhibit telomerase reactivation specifically cells. Our work uses genome-wide functional screens identify 30 specific regulators promoters. These candidates identified from screening serve as an excellent resource understand how is reactivated and targets for making inhibitors...
The DNMT2 enzyme methylates tRNA-Asp at position C38. Because there is no tRNA–Dnmt2 cocrystal structure available, we have mapped the tRNA binding site of by systematically mutating surface-exposed lysine and arginine residues to alanine studying methylation activity corresponding variants. After 20 residues, identified eight them that caused large (>4-fold) decreases in catalytic activity. These cluster within next a surface cleft protein, which enough accommodate anticodon loop stem. This...
<div>Abstract<p>Over-consumption of iron-rich red meat and hereditary or genetic iron overload are associated with an increased risk colorectal carcinogenesis, yet the mechanistic basis how metal-mediated signaling leads to oncogenesis remains enigmatic. Using fresh cancer samples we identify Pirin, sensor, that overcomes a rate-limiting step in oncogenesis, by reactivating dormant human telomerase reverse transcriptase (hTERT) subunit holoenzyme...
<p>ITDRF-CETSA method identifying SP2509’s target.</p>
<p>SP2509 competes with Iron-(Fe<sup>3+</sup>) bound to Pirin</p>
<p>Role of Iron-(Fe<sup>3+</sup>) and Pirin in CRC</p>
<p>Effect of LSD1 on hTERT expression and telomerase activity.</p>
<p>Role of Iron-(Fe<sup>3+</sup>) and Pirin in CRC</p>
<p>Regulation of Sp1 and FBXW7 levels by Pirin SP2509</p>
<p>Iron-(Fe3+) bound to Pirin positively regulates hTERT</p>
<p>Validation of reporter cell lines for small molecule screens.</p>
<p>Iron-(Fe<sup>3+</sup>) regulates hTERT via Pirin-mediated control of FBXW7, the Sp1 targeting E3 ligase</p>