Lars M. Steinmetz
Stanford University
GeneMolecular biologyTranscription (biology)GeneticsBiology
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Publications 190
#1Qing Liu (Stanford University)H-Index: 3
#2Haodi Wu (Stanford University)H-Index: 20
Last. David Marciano (Stanford University)H-Index: 18
view all 27 authors...
Maternal drug exposure during pregnancy increases the risks of developmental cardiotoxicity, leading to congenital heart defects (CHDs). In this study, we used human stem cells as an in-vitro system to interrogate the mechanisms underlying drug-induced toxicity during cardiomyocyte differentiation, including anticancer tyrosine kinase inhibitor (TKI) drugs (imatinib, sunitinib, and vandetanib). H1-ESCs were treated with these drugs at sublethal levels during cardiomyocyte differentiation. We fou...
#1William F. MuellerH-Index: 2
#2Petra JakobH-Index: 4
Last. Bettina HaaseH-Index: 7
view all 16 authors...
N-Glycanase 1 (NGLY1) deficiency is an ultra-rare, complex and devastating neuromuscular disease, with multi-organ symptoms. NGLY1 is a deglycosylating protein involved in the degradation of misfolded proteins retrotranslocated from the endoplasmic reticulum (ER). We show that the loss of NGLY1 causes substantial changes in the RNA and protein landscape of K562 cells. We employed the CMap database to predict compounds that can modulate NGLY1 activity. Utilizing our robust K562 screening system, ...
#1Haruhiko Fujihira (Juntendo University)H-Index: 4
Last. Tadashi SuzukiH-Index: 26
view all 16 authors...
Abstract The cytoplasmic peptide:N-glycanase (Ngly1) is a de-N-glycosylating enzyme that cleaves N-glycans from misfolded glycoproteins and is involved in endoplasmic reticulum-associated degradation. The recent discovery of NGLY1-deficiency, which causes severe systemic symptoms, drew attention to the physiological function of Ngly1 in mammals. While several studies have been carried out to reveal the physiological necessity of Ngly1, the semi-lethal nature of Ngly1-deficient animals made it di...
#1Andreas Trumpp (DKFZ: German Cancer Research Center)H-Index: 56
#2L Becker (DKFZ: German Cancer Research Center)H-Index: 1
Last. Sarah Jauch (DKFZ: German Cancer Research Center)
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Although the survival of patients diagnosed with breast cancer has greatly improved over the last decades, the metastatic stage of the disease still remains incurable. Blood circulating tumor cells (CTCs) are assumed to be the source for metastatic onset and the enumeration of CTCs has already proven its prognostic value for survival in metastatic breast cancer (mBC) patients. However, the biological profiles of CTCs are so far not considered in therapy selection, but hold the potential to displ...
#1Semih Calamak (Stanford University)H-Index: 10
#2Menekse Ermis (Stanford University)H-Index: 3
Last. Utkan Demirci (Stanford University)H-Index: 56
view all 9 authors...
1 CitationsSource
#1Chiara Baccin (Heidelberg University)H-Index: 1
#2Jude Al-SabahH-Index: 1
Last. Simon HaasH-Index: 13
view all 10 authors...
The bone marrow constitutes the primary site for life-long blood production and skeletal regeneration. However, its cellular and spatial organization remains controversial. Here, we combine single-cell and spatially resolved transcriptomics to systematically map the molecular, cellular and spatial composition of distinct bone marrow niches. This allowed us to transcriptionally profile all major bone-marrow-resident cell types, determine their localization and clarify sources of pro-haematopoieti...
8 CitationsSource
#1Cristina Vieitez (EMBL-EBI: European Bioinformatics Institute)H-Index: 3
#2Bede P. Busby (EMBL-EBI: European Bioinformatics Institute)H-Index: 3
Last. Pedro Beltrao (EMBL-EBI: European Bioinformatics Institute)H-Index: 24
view all 16 authors...
Phosphorylation is a critical post-translational modification involved in the regulation of almost all cellular processes. However, less than 5% of thousands of recently discovered phosphorylation sites have a known function. Here, we devised a chemical genetic approach to study the functional relevance of phosphorylation in S. cerevisiae. We generated 474 phospho-deficient mutants that, along with the gene deletion library, were screened for fitness in 102 conditions. Of these, 42% exhibited gr...
1 CitationsSource
#1Jingwen Wang (KI: Karolinska Institutet)
#2Bingnan Li (KI: Karolinska Institutet)H-Index: 1
Last. Vicent Pelechano (KI: Karolinska Institutet)H-Index: 22
view all 6 authors...
Eukaryotic transcriptomes are complex involving thousands of overlapping transcripts. The interleaved nature of the transcriptome complicates its annotation, limits our ability to identify regulatory regions and, in some cases, can lead to misinterpretation of gene expression. To improve the annotation of complex genomes, we have developed an optimized method, TIF-Seq2, able to sequence simultaneously the 5′ and 3′ end of individual mRNA molecules at single-nucleotide resolution. We investigate ...
#1Wu WeiH-Index: 17
#2Bianca P. HennigH-Index: 2
Last. Vicent PelechanoH-Index: 22
view all 10 authors...
Cryptic transcription is widespread and generates a heterogeneous group of RNA molecules of unknown function. To improve our understanding of cryptic transcription, we investigated their transcription start site (TSS) usage, chromatin organization, and posttranscriptional consequences in Saccharomyces cerevisiae We show that TSSs of chromatin-sensitive internal cryptic transcripts retain comparable features of canonical TSSs in terms of DNA sequence, directionality, and chromatin accessibility. ...
2 CitationsSource
#1Arne H. SmitsH-Index: 16
Last. Wolfgang HuberH-Index: 76
view all 18 authors...
Gene knock outs (KOs) are efficiently engineered through CRISPR–Cas9-induced frameshift mutations. While the efficiency of DNA editing is readily verified by DNA sequencing, a systematic understanding of the efficiency of protein elimination has been lacking. Here we devised an experimental strategy combining RNA sequencing and triple-stage mass spectrometry to characterize 193 genetically verified deletions targeting 136 distinct genes generated by CRISPR-induced frameshifts in HAP1 cells. We o...
12 CitationsSource