R. Koche

Interferon response and epigenetic modulation by SMARCA4 mutations drive ovarian tumor immunogenicity

This study shows that SMARCA4 mutations in ovarian cancer increase immunogenicity through interferon response and epigenetic changes, enhancing T cell and NK cell activity in the tumor microenvironment.

Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance

This study identifies a quiescent label-retaining cell population in human AML that drives disease and therapy resistance through epigenetic mechanisms.

Amplicon structure creates collateral therapeutic vulnerability in cancer

The paper identifies DDX1 as a passenger gene co-amplified with MYCN in cancer, showing that its aberrant expression creates a therapeutic vulnerability through mTORC1 dependency.

Oncogenic IDH mutations increase heterochromatin-related replication stress without impacting tumor mutation burden

This study shows that IDH mutations cause replication stress through heterochromatin, affecting DNA repair and PARP inhibitor response without increasing mutation burden.

Epigenetic plasticity cooperates with emergent cell-cell interactions to drive neoplastic tissue remodeling in the pancreas

The paper uses single-cell analysis to show that epigenetic plasticity and cell-cell interactions drive tissue remodeling in early pancreatic cancer.

An integrated approach to study chromatin and transcriptional dynamics throughout the cell cycle without pharmacological inhibition

The paper compares chromatin and transcriptional dynamics across cell cycle phases in mESCs using different synchronization methods, finding that CDK1 inhibitor synchronization best mimics G2/M phase.

Jak2V617F Reversible Activation Shows an Essential Requirement for Jak2V617F in Myeloproliferative Neoplasms

This study shows that reversible activation of Jak2V617F in a mouse model demonstrates its essential role in myeloproliferative neoplasms and highlights the therapeutic potential of mutant-specific JAK2 inhibition.

CXCL8/CXCR2 signaling mediates bone marrow fibrosis and represents a therapeutic target in myelofibrosis

This study identifies CXCL8/CXCR2 signaling as a driver of bone marrow fibrosis in myelofibrosis and shows its therapeutic potential through genetic and pharmacologic inhibition.

An epigenetic memory of inflammation controls context-dependent lineage plasticity in the pancreas

This study shows that inflammation leaves an epigenetic memory in pancreatic acinar cells, affecting their lineage plasticity and tumorigenesis in response to subsequent stress.

Plasmacytoid dendritic cell expansion defines a distinct subset of RUNX1 mutated acute myeloid leukemia

This study identifies pDC-AML as a distinct AML subset with high RUNX1 mutations and pDC transcriptional features, suggesting CD123 targeting as a therapeutic strategy.

Anatomic position determines oncogenic specificity in melanoma

The paper shows that anatomic position influences oncogenic specificity in melanoma by identifying position-specific gene programs that interact with oncogenes like CRKL.

Developmental chromatin programs determine oncogenic competence in melanoma

The paper shows that BRAFV600E transforming ability depends on the cell of origin's transcriptional program, with neural crest and melanoblasts being more susceptible due to higher chromatin modifying enzyme expression and ATAD2-SOX10 complex formation.

Stag1 and Stag2 regulate cell fate decisions in hematopoiesis through non-redundant topological control

The paper shows Stag2 loss in HSPCs impairs B-cell lineage commitment by reducing chromatin accessibility, while Stag1 cannot restore this function despite rescuing topological domains.

Peptidomimetic blockade of MYB in acute myeloid leukemia

This study develops a peptidomimetic inhibitor, MYBMIM, that blocks MYB:CBP/P300 complex assembly in AML cells, leading to apoptosis and reduced tumor growth in mice.

Human PGBD5 DNA transposase promotes site-specific oncogenic mutations in rhabdoid tumors

This study identifies PGBD5 as an oncogenic DNA transposase in rhabdoid tumors, causing site-specific genomic rearrangements through PSS sequences and end-joining repair.

MEF2C phosphorylation is required for chemotherapy resistance in acute myeloid leukemia

This study identifies MEF2C phosphorylation as a marker of chemotherapy resistance in AML and shows that inhibiting this phosphorylation can overcome resistance in MEF2C-activated cells.