Richard P. Koche

Timed binary WNT activity is sufficient to model the early human neural axis

This paper shows that timed WNT pulses can specify distinct neural domains in human pluripotent stem cells, enabling the generation of specific neuron and progenitor types.

Quantitative and sensitive neuroblastoma minimal residual disease detection using extrachromosomal DNA (ecDNA) breakpoints

This study develops a method to detect minimal residual disease in neuroblastoma using ecDNA breakpoints, achieving high sensitivity and specificity in bone marrow samples.

Extracellular matrix regulates lineage plasticity in prostate cancer through YAP/TEAD

Loss of extracellular matrix-integrin signaling switches off YAP/TEAD and lets prostate adenocarcinoma organoids turn neuroendocrine; LATS inhibition reverses it, and combined YAP, NOTCH and AR inhibition fully reprograms them.

Squamous-state excursions activate APOBEC3A in cancer

The paper identifies transient squamous-state excursions in cancer cells as a source of APOBEC3A mutagenesis, linking it to lineage-state plasticity rather than persistent inflammation.

MYC pathway reprogramming through a TIP60 coactivator switch in neuroendocrine lineage transition in prostate cancer

The paper identifies a TIP60 coactivator switch in neuroendocrine prostate cancer, revealing a therapeutic target for MYC-driven diseases.

Mitochondrial ATP production promotes T cell differentiation and function by regulating chromatin accessibility

This study shows that mitochondrial ATP production, induced by D-α-hydroxybutyrate, promotes T cell differentiation and function by regulating chromatin accessibility and gene expression.

TET2 and TP53 Mutations Cooperatively Modulate the Response to Inflammation to Promote Leukemic Transformation

This study shows that TET2 and TP53 mutations work together to promote leukemic transformation by altering inflammatory responses and chemotherapy tolerance in hematopoietic stem cells.

p53 enables phospholipid headgroup scavenging

This study shows p53 enables lipid headgroup recycling during senescence by increasing phosphoethanolamine supply through autophagy and lysosomal catabolism, revealing a metabolic vulnerability in p53-activated cells.

The regenerative potential of adult Nestin+ cerebellar astroglia is limited compared to in neonates

This study shows adult Nestin+ cerebellar astroglia have limited regenerative potential compared to neonatal cells, with ATAC-seq revealing developmental gene silencing as a key factor.

Transcription factors SP5 and SP8 drive primary cilia formation

This study identifies SP5 and SP8 as transcription factors that drive primary cilia formation through genetic and transcriptomic analyses in mouse embryos.

L1CAM signaling through planar cell polarity generates SOX2+ metastatic progenitors in lung adenocarcinoma

The paper identifies L1CAM-driven planar cell polarity signaling as a mechanism promoting SOX2+ metastatic progenitors in lung adenocarcinoma.

Loss of tumor cell MHC Class II drives insensitivity of BRAF-mutant anaplastic thyroid cancers to MAPK inhibitors

This study shows that loss of MHC Class II in BRAF-mutant anaplastic thyroid cancers leads to resistance to MAPK inhibitors by reducing CD4+ T-cell activation.

An increase in reactive oxygen species underlies neonatal cerebellum repair

This study shows that reactive oxygen species (ROS) increase in the neonatal cerebellum after injury, and reducing ROS impairs regenerative processes.

Chromatin architecture mapping by multiplex proximity tagging

This paper introduces a proximity-tagging method called PCP to map chromatin architecture in yeast, revealing nucleosome organization and long-range interactions.

TAD hierarchy restricts poised LTR activation and loss of TAD hierarchy promotes LTR co-option in cancer

The paper shows that TAD hierarchy restricts LTR activation, and its loss in cancer allows LTRs to act as alternative promoters, driving oncogene activation and transcriptional diversity.

Sequential transcriptional gates in the thalamo-cortical circuit coordinate memory stabilization

The paper identifies a sequential transcriptional cascade in the thalamo-cortical circuit that enables memory stabilization over time.

Extrachromosomal DNA micronucleation constrains tumour fitness andimproves patient survival

This study shows that ecDNA mis-segregation leads to micronuclei formation, reduced oncogene transcription, and improved patient survival in neuroblastoma.

Altered chromatin accessibility mediated by somatic cohesin mutations amplifies FLI1-Menin output to promote leukemogenesis

This study shows that cohesin mutations alter chromatin accessibility, enhancing FLI1-Menin interaction and promoting leukemogenesis through therapeutic vulnerabilities.

Genetic variation modulates susceptibility to aberrant DNA hypomethylation and imprint deregulation in naive pluripotent stem cells

The paper identifies genetic variants that influence DNA methylation stability and imprint deregulation in naive pluripotent stem cells across different mouse strains.

A nucleosome switch primes Hepatitis B Virus infection

This study identifies a nucleosome switch that primes Hepatitis B Virus infection by driving X gene transcription and shows that CBL137 inhibits this process.

Mitotic transcription ensures ecDNA inheritance through chromosomal tethering

The paper shows that ecDNA inheritance is ensured through mitotic transcription and chromosomal tethering via BRD4 and PVT1, preventing cytosolic mis-segregation and chromosomal integration.

A pathogenic subpopulation of human glioma associated macrophages linked to glioma progression

This study identifies a pathogenic subpopulation of glioma-associated macrophages (mGAMs) linked to glioma progression through GRN analysis and functional validation.

Aging limits stemness and tumorigenesis in the lung by reprogramming iron homeostasis

This study shows aging reduces lung stem cell function and suppresses lung cancer by inducing iron deficiency through the NUPR1-lipocalin-2 pathway.

Retinoid X Receptor Signaling Mediates Cancer Cell Lipid Metabolism in the Leptomeninges

This study identifies RXR signaling as a mediator of lipid metabolism in leptomeningeal metastatic cancer cells, revealing a potential therapeutic target.

Targetable Treatment Resistance in Thyroid Cancer with Clonal Hematopoiesis

This study identifies TET2-mutant clonal hematopoiesis in thyroid cancer microenvironments and shows that TGFβ signaling from these macrophages mediates resistance to BRAF/MEK inhibition, with TGFβ inhibition restoring sensitivity.

Mutant IDH uncouples p53 from target gene regulation to disable tumor suppression

This paper shows that mutant IDH disrupts p53 target gene regulation by altering chromatin states, disabling tumor suppression, and that this effect can be reversed with IDH inhibition.

A pluripotent stem cell platform for in vitro systems genetics studies of mouse development

This paper establishes a pluripotent stem cell platform using genetically diverse mouse lines to study the impact of natural genetic variation on development and gene regulation.

An epigenetic barrier sets the timing of human neuronal maturation

Chromatin regulators including EZH2, EHMT1/2, and DOT1L establish an epigenetic barrier in human neural progenitors that poises maturation genes and sets the protracted pace of cortical neuron maturation.

HiC-DC+: systematic 3D interaction calls and differential analysis for Hi-C and HiChIP

HiC-DC+ is a tool for Hi-C/HiChIP interaction calling and differential analysis, showing improved performance in HiChIP benchmarking and revealing 3D organization changes during cohesin perturbation and differentiation.