Ruben Dries

Ruben Dries
Dana-Farber Cancer Institute | DFCI · Department of Biostatistics and Computational Biology

PhD

About

71
Publications
11,494
Reads
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2,606
Citations
Additional affiliations
September 2013 - January 2016
Erasmus MC
Position
  • PhD Student
September 2009 - October 2013
KU Leuven
Position
  • PhD Student

Publications

Publications (71)
Article
Full-text available
Apart from the anti-GD2 antibody, immunotherapy for neuroblastoma has had limited success due to immune evasion mechanisms, coupled with an incomplete understanding of predictors of response. Here, from bulk and single-cell transcriptomic analyses, we identify a subset of neuroblastomas enriched for transcripts associated with immune activation and...
Article
Spatial transcriptomic technologies have been developed rapidly in recent years. The addition of spatial context to expression data holds the potential to revolutionize many fields in biology. However, the lack of computational tools remains a bottleneck that is preventing the broader utilization of these technologies. Recently, we have developed G...
Article
Full-text available
The human hematopoietic stem cell harbors remarkable regenerative potential that can be harnessed therapeutically. During early development, hematopoietic stem cells in the fetal liver undergo active expansion while simultaneously retaining robust engraftment capacity, yet the underlying molecular program responsible for their efficient engraftment...
Article
Spatial transcriptomics is a rapidly growing field that promises to comprehensively characterize tissue organization and architecture at the single-cell or subcellular resolution. Such information provides a solid foundation for mechanistic understanding of many biological processes in both health and disease that cannot be obtained by using tradit...
Article
Full-text available
http://deepblue.lib.umich.edu/bitstream/2027.42/173869/1/13059_2021_Article_2468.pdf
Article
Full-text available
http://deepblue.lib.umich.edu/bitstream/2027.42/173868/1/13059_2021_Article_2433.pdf
Article
Insights into the remarkable engraftment potential of fetal liver (FL) hematopoietic stem cells (HSCs) could be harnessed to improve ex vivo HSC expansion, increase engraftment efficiency, and enable in vitro HSC generation. Using CITE-seq, a technique that combines single cell RNA sequencing with oligo-tagged antibodies, we profiled 26,407 FL cell...
Article
Full-text available
Although activating mutations of the anaplastic lymphoma kinase (ALK) membrane receptor occur in ∼10% of neuroblastoma (NB) tumors, the role of the wild-type (WT) receptor, which is aberrantly expressed in most non-mutated cases, is unclear. Both WT and mutant proteins undergo extracellular domain (ECD) cleavage. Here, we map the cleavage site to A...
Article
Full-text available
Cyclin-dependent kinase 12 (CDK12) is an emerging therapeutic target due to its role in regulating transcription of DNA-damage response (DDR) genes. However, development of selective small molecules targeting CDK12 has been challenging due to the high degree of homology between kinase domains of CDK12 and other transcriptional CDKs, most notably CD...
Article
Full-text available
Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive and open-source toolbox for spatial data analysis and visualization. The analysis module provides end-to-end analysis by implementing a wide range of algorithms for characte...
Preprint
Full-text available
Immunotherapy for patients with neuroblastoma has met with limited success, partly due to an incomplete understanding of the mechanisms underlying immune responsiveness in this clinically and genetically heterogenic tumor. Here, we undertook an unbiased analysis using dimension reduction and UMAP visualization of transcriptional signatures derived...
Preprint
Full-text available
The rapid development of novel spatial transcriptomic and proteomic technologies has provided new opportunities to investigate the interactions between cells and their native microenvironment. However, effective use of such technologies requires the development of innovative computational tools that are easily accessible and intuitive to use. Here...
Preprint
Full-text available
The human hematopoietic stem cell (HSC) harbors remarkable regenerative potential that can be harnessed therapeutically. During early development, HSCs in the fetal liver (FL) undergo active expansion while simultaneously retaining robust engraftment capacity, yet the underlying molecular program responsible for their efficient engraftment remains...
Article
Intro: The complex and tightly regulated process of human hematopoietic development culminates in the production of hematopoietic stem cells (HSCs), which subsequently acquire functional competence and undergo expansion in the fetal liver (FL). The establishment of a high-resolution molecular signature of FL HSCs provides insights into HSC biology...
Article
The transcription factor Zeb2 controls fate specification and subsequent differentiation and maturation of multiple cell types in various embryonic tissues. It binds many protein partners, including activated Smad proteins and the NuRD co-repressor complex. How Zeb2 subdomains support cell differentiation in various contexts has remained elusive. H...
Article
Cyclin-dependent kinase 7 (CDK7) is a central regulator of the cell cycle and gene transcription. However, little is known about its impact on genomic instability and cancer immunity. Using a selective CDK7 inhibitor, YKL-5-124, we demonstrated that CDK7 inhibition predominately disrupts cell-cycle progression and induces DNA replication stress and...
Article
Full-text available
Cooperative actions of extrinsic signals and cell-intrinsic transcription factors alter gene regulatory networks enabling cells to respond appropriately to environmental cues. Signaling by Transforming Growth Factor type β (TGFβ) family ligands (eg, bone morphogenetic proteins [BMPs] and Activin/Nodal) exerts cell-type specific and context-dependen...
Article
Full-text available
Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolu...
Article
Full-text available
Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolu...
Article
Full-text available
The CCCTC-binding factor (CTCF), which anchors DNA loops that organize the genome into structural domains, has a central role in gene control by facilitating or constraining interactions between genes and their regulatory elements1,2. In cancer cells, the disruption of CTCF binding at specific loci by somatic mutation3,4 or DNA hypermethylation⁵ re...
Preprint
Full-text available
The rapid development of novel spatial transcriptomics technologies has provided new opportunities to investigate the interactions between cells and their native microenvironment. However, effective use of such technologies requires the development of innovative computational algorithms and pipelines. Here we present Giotto, a comprehensive, flexib...
Article
The rapid development of novel spatial transcriptomics technologies has provided new opportunities to investigate the interactions between cells and their native microenvironment. However, effective use of such technologies requires the development of innovative computational algorithms and pipelines. Here we present Giotto, a comprehensive, flexib...
Article
Full-text available
Background: Single-cell RNA-sequencing technologies provide a powerful tool for systematic dissection of cellular heterogeneity. However, the prevalence of dropout events imposes complications during data analysis and, despite numerous efforts from the community, this challenge has yet to be solved. Results: Here we present a computational metho...
Article
Full-text available
Cyclin-dependent kinase 12 (CDK12) modulates transcription elongation by phosphorylating the carboxy-terminal domain of RNA polymerase II and selectively affects the expression of genes involved in the DNA damage response (DDR) and mRNA processing. Yet, the mechanisms underlying such selectivity remain unclear. Here we show that CDK12 inhibition in...
Article
Full-text available
Imaging the transcriptome in situ with high accuracy has been a major challenge in single-cell biology, which is particularly hindered by the limits of optical resolution and the density of transcripts in single cells1–5. Here we demonstrate an evolution of sequential fluorescence in situ hybridization (seqFISH+). We show that seqFISH+ can image mR...
Article
Full-text available
How intrinsic gene-regulatory networks interact with a cell's spatial environment to define its identity remains poorly understood. We developed an approach to distinguish between intrinsic and extrinsic effects on global gene expression by integrating analysis of sequencing-based and imaging-based single-cell transcriptomic profiles, using cross-p...
Preprint
Full-text available
The cyclin-dependent kinase 12 (CDK12) modulates transcription elongation by phosphorylating the carboxy-terminal domain of RNA polymerase II and appears to selectively affect the expression of DNA damage response (DDR) and mRNA processing genes. Yet, the mechanism(s) by which it achieves this selectivity remains unclear. Using a highly selective C...
Preprint
Both the intrinsic regulatory network and spatial environment are contributors of cellular identity and result in cell state variations. However, their individual contributions remain poorly understood. Here we present a systematic approach to integrate both sequencing-and imaging-based single-cell transcriptomic profiles, thereby combining whole-t...
Article
Introduction: Small cell lung cancer (SCLC) is a common and rapidly fatal malignancy for which no biomarker-targeted therapies have been developed. Despite a critical need, progress suffers from (1) scarcity of cutting-edge laboratory models and (2) absence of promising targets. Patient-derived xenografts (PDX) may faithfully model the clinical dis...
Article
Small cell lung cancer (SCLC) has the highest malignancy among all lung cancers, exhibiting aggressive growth and early metastasis to distant sites. For 30 years, treatment options for SCLC have been limited to chemotherapy, warranting the need for more effective treatments. Frequent inactivation of TP53 and RB1 as well as histone dysmodifications...
Article
Full-text available
Both the intrinsic regulatory network and spatial environment are contributors of cellular identity and result in cell state variations. However, their individual contributions remain poorly understood. Here we present a systematic approach to integrate both sequencing- and imaging-based single-cell transcriptomic profiles, thereby combining whole-...
Article
Full-text available
Small cell lung cancer (SCLC) patient-derived xenografts (PDX) can be generated from biopsies or circulating tumor cells (CTC), though scarcity of tissue and low efficiency of tumor growth have previously limited these approaches. Applying an established clinical–translational pipeline for tissue collection and an automated microfluidic platform fo...
Article
Full-text available
Immune checkpoint blockade, exemplified by antibodies targeting the programmed death-1 (PD-1) receptor, can induce durable tumor regressions in some patients. To enhance the efficacy of existing immunotherapies, we screened for small molecules capable of increasing the activity of T cells suppressed by PD-1. Here, we show that short-term exposure t...
Article
Full-text available
Hypothesis: Proinflammatory cytokine Interleukin (IL)-17A (IL-17A) is overexpressed in a subset of patients with lung cancer. We hypothesized that IL-17A promotes a pro-tumorigenic inflammatory phenotype, and inhibits anti-tumor immune responses. Experimental design: We generated bi-transgenic mice expressing a conditional IL-17A allele along wi...
Article
Full-text available
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the im...
Article
Full-text available
In human ESCs the transcription factor Zeb2 regulates neuroectoderm versus mesendoderm formation, but it is unclear how Zeb2 affects the global transcriptional regulatory network in these cell-fate decisions. We generated Zeb2 knockout (KO) mouse ESCs, subjected them as embryoid bodies (EBs) to neural and general differentiation and carried out tem...
Article
Full-text available
BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive...
Article
Full-text available
Naive mouse embryonic stem cells (mESCs) are in a metastable state and fluctuate between inner cell mass- and epiblast-like phenotypes. Here, we show transient activation of the BMP-SMAD signaling pathway in mESCs containing a BMP-SMAD responsive reporter transgene. Activation of the BMP-SMAD reporter transgene in naive mESCs correlated with lower...
Data
Table S1. Differentially Expressed Genes between GFP++ and GFP− BRE:gfp mESCs and between S1fl/flS5fl/fl and S1−/−S5−/− mESCs
Data
Table S2. Differential DNA Methylation between GFP++ and GFP− BRE:gfp mESCs and between S1fl/flS5fl/fl and S1−/−S5−/− mESCs