Kevin A. Janssen
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View article: Hepatocyte mitochondrial NAD+ content is limiting for liver regeneration
Hepatocyte mitochondrial NAD+ content is limiting for liver regeneration Open
Nicotinamide adenine dinucleotide (NAD + ) precursor supplementation shows metabolic and functional benefits in rodent models of disease and is being explored as potential therapeutic strategy in humans. However, the wide range of processe…
View article: A mouse model of MEPAN demonstrates a role for mitochondrial fatty acid synthesis in iron–sulfur cluster and supercomplex formation
A mouse model of MEPAN demonstrates a role for mitochondrial fatty acid synthesis in iron–sulfur cluster and supercomplex formation Open
MEPAN ( M itochondrial E noyl CoA Reductase P rotein- A ssociated N eurodegeneration) is an early-onset movement disorder characterized by ataxia, dysarthria, and optic atrophy. Here, we report the creation of a mouse model of MEPAN with p…
View article: Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes.
Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes. Open
Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are…
View article: Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes
Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes Open
Lethal COVID-19 outcomes are attributed to classic cytokine storm. We revisit this using RNA sequencing of nasopharyngeal and 40 autopsy samples from patients dying of SARS-CoV-2. Subsets of the 100 top-upregulated genes in nasal swabs are…
View article: A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies
A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies Open
Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2P95H/+ mutation disrupts the splicing of mitochondr…
View article: Lethal COVID-19 Associates With RAAS-Induced Inflammation For Multiple Organ Damage Including Mediastinal Lymph Nodes
Lethal COVID-19 Associates With RAAS-Induced Inflammation For Multiple Organ Damage Including Mediastinal Lymph Nodes Open
Lethal COVID-19 outcomes are most often attributed to classic cytokine storm and attendant excessive immune signaling. We re-visit this question using RNA sequencing in nasopharyngeal and 40 autopsy samples from COVID-19-positive and negat…
View article: A mitochondrial surveillance mechanism activated by<i>SRSF2</i>mutations in hematologic malignancies
A mitochondrial surveillance mechanism activated by<i>SRSF2</i>mutations in hematologic malignancies Open
Splicing factor mutations are common in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but how they alter cellular functions is unclear. We show that the pathogenic SRSF2 P95H/+ mutation disrupts the splicing of mitochond…
View article: Combination of common mtDNA variants results in mitochondrial dysfunction and a connective tissue dysregulation
Combination of common mtDNA variants results in mitochondrial dysfunction and a connective tissue dysregulation Open
Mitochondrial dysfunction can be associated with a range of clinical manifestations. Here, we report a family with a complex phenotype including combinations of connective tissue, neurological, and metabolic symptoms that were passed on to…
View article: Permethylation of Ribonucleosides Provides Enhanced Mass Spectrometry Quantification of Post-Transcriptional RNA Modifications
Permethylation of Ribonucleosides Provides Enhanced Mass Spectrometry Quantification of Post-Transcriptional RNA Modifications Open
Chemical modifications of RNA are associated with fundamental biological processes such as RNA splicing, export, translation, and degradation, as well as human disease states, such as cancer. However, the analysis of ribonucleoside modific…
View article: Data-Independent Acquisition for the Detection of Mononucleoside RNA Modifications by Mass Spectrometry
Data-Independent Acquisition for the Detection of Mononucleoside RNA Modifications by Mass Spectrometry Open
RNA is dynamically modified in cells by a plethora of chemical moieties to modulate molecular functions and processes. Over 140 modifications have been identified across species and RNA types, with the highest density and diversity of modi…
View article: Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree
Novel mtDNA Imparts the Connective Tissue Disorder of a Tourette Pedigree Open
Mitochondrial dysfunction is associated with a range of clinical manifestations including neuropsychiatric and metabolic disorder. Here, we reanalyzed a family with an L-Histidine Decarboxylase (HDC) variant previously linked to Tourette s…
View article: Permethylation of ribonucleosides provides enhanced mass spectrometry quantification of post-transcriptional modifications
Permethylation of ribonucleosides provides enhanced mass spectrometry quantification of post-transcriptional modifications Open
Chemical modifications of RNA are associated with fundamental biological processes such as RNA splicing, export, translation, degradation, as well as human disease states such as cancer. However, the analysis of ribonucleoside modification…
View article: Dynamic changes in RNA–protein interactions and RNA secondary structure in mammalian erythropoiesis
Dynamic changes in RNA–protein interactions and RNA secondary structure in mammalian erythropoiesis Open
Two features of eukaryotic RNA molecules that regulate their post-transcriptional fates are RNA secondary structure and RNA-binding protein (RBP) interaction sites. However, a comprehensive global overview of the dynamic nature of these se…
View article: Combinatorial Histone H3 Modifications Are Dynamically Altered in Distinct Cell Cycle Phases
Combinatorial Histone H3 Modifications Are Dynamically Altered in Distinct Cell Cycle Phases Open
The cell cycle is a highly regulated and evolutionary conserved process that results in the duplication of cell content and the equal distribution of the duplicated chromosomes into a pair of daughter cells. Histones are fundamental struct…
View article: Histone H3.3 beyond cancer: Germline mutations in <i>Histone 3 Family 3A and 3B</i> cause a previously unidentified neurodegenerative disorder in 46 patients
Histone H3.3 beyond cancer: Germline mutations in <i>Histone 3 Family 3A and 3B</i> cause a previously unidentified neurodegenerative disorder in 46 patients Open
Germ line mutations in H3F3A and H3F3B cause a previously unidentified neurodevelopmental syndrome.
View article: TET2 chemically modifies tRNAs and regulates tRNA fragment levels
TET2 chemically modifies tRNAs and regulates tRNA fragment levels Open
View article: N<sup>6</sup>‐methyladenosine and RNA secondary structure affect transcript stability and protein abundance during systemic salt stress in Arabidopsis
N<sup>6</sup>‐methyladenosine and RNA secondary structure affect transcript stability and protein abundance during systemic salt stress in Arabidopsis Open
After transcription, a messenger RNA (mRNA) is further post‐transcriptionally regulated by several features including RNA secondary structure and covalent RNA modifications (specifically N 6 ‐methyladenosine, m 6 A). Both RNA secondary str…
View article: Mass Spectrometry Methods For Enhanced Analysis Of Epigenetic And Epitranscriptomic Modifications
Mass Spectrometry Methods For Enhanced Analysis Of Epigenetic And Epitranscriptomic Modifications Open
Epigenetic and epitranscriptomic mechanisms play critical roles in regulating transcription and translation, among other cellular functions. One of the most important ways this is performed is through chemical modification of proteins, suc…
View article: RNA mass spectrometry on WT, Tet2 KO, and Tet1/2/3 tKO mouse embryonic stem cells
RNA mass spectrometry on WT, Tet2 KO, and Tet1/2/3 tKO mouse embryonic stem cells Open
Mass spectrometry for total, size selected small RNAs (< 200 nts), and gel-purified tRNAs in wild type, Tet2 single KO, and Tet1/2/3 triple KO mouse embryonic stem cells. As shown in Fig. 4A–B and Extended Data Fig. 4D of "TET2 chemical…
View article: Mass spectrometry on tRNAs from Tet1/2/3 tKO mESCs rescued with TET2 WT or catalytic mutant (HxD) and control (GFP)
Mass spectrometry on tRNAs from Tet1/2/3 tKO mESCs rescued with TET2 WT or catalytic mutant (HxD) and control (GFP) Open
Mass spectrometry analysis on tRNAs gel purified from Tet1/2/3 triple KO mouse embryonic stem cells after transient transfection of TET2 catalytic fragment wild type (WT), catalytic mutant (HxD), or a GFP as a negative control. As shown in…
View article: RNA mass spectrometry of tRNAs after incubation with recombinant TET2
RNA mass spectrometry of tRNAs after incubation with recombinant TET2 Open
Mass spectrometry on purified tRNA after incubation with recombinant TET2 catalytic fragment or control reactions. As shown in Fig. 4F of "TET2 chemically modifies tRNAs and regulates tRNA fragment levels" by He et al.
View article: Regulation of nuclear epigenome by mitochondrial DNA heteroplasmy
Regulation of nuclear epigenome by mitochondrial DNA heteroplasmy Open
Diseases associated with mitochondrial DNA (mtDNA) mutations are highly variable in phenotype, in large part because of differences in the percentage of normal and mutant mtDNAs (heteroplasmy) present within the cell. For example, increasi…
View article: One minute analysis of 200 histone posttranslational modifications by direct injection mass spectrometry
One minute analysis of 200 histone posttranslational modifications by direct injection mass spectrometry Open
DNA and histone proteins define the structure and composition of chromatin. Histone posttranslational modifications (PTMs) are covalent chemical groups capable of modeling chromatin accessibility, mostly due to their ability in recruiting …
View article: EpiProfile 2.0: A Computational Platform for Processing Epi-Proteomics Mass Spectrometry Data
EpiProfile 2.0: A Computational Platform for Processing Epi-Proteomics Mass Spectrometry Data Open
Epigenetics has become a fundamental scientific discipline with various implications for biology and medicine. Epigenetic marks, mostly DNA methylation and histone post-translational modifications (PTMs), play important roles in chromatin …
View article: Recent Achievements in Characterizing the Histone Code and Approaches to Integrating Epigenomics and Systems Biology
Recent Achievements in Characterizing the Histone Code and Approaches to Integrating Epigenomics and Systems Biology Open