Van Andel Institute

Early metabolic rewiring precedes arsenic-induced carcinogenesis in human lung epithelial cells

Chronic, low-dose inorganic arsenic (iAs) exposure is a major environmental risk factor for lung cancer, yet the early cellular events that link low-dose exposure to carcinogenesis remain poorly understood. Because most people are exposed to iAs at low, chronic doses rather than...

Cryo-EM structures of autoinhibited and RNA-activated ZNFX1 helicase

Abstract ZNFX1 is an RNA helicase that plays a critical role in host defense against viral infections. Recent studies further revealed that ZNFX1 harbors an unexpected RNA-ubiquitinating E3 ligase activity, raising fundamental questions about how RNA-binding activates this multif...

Oral vitamin C supplementation in patients with clonal cytopenia of undetermined significance or lower‐risk myeloid malignancies: Results from EVITA, a phase 2 randomized, placebo‐controlled trial

BACKGROUND: Vitamin C (VitC) is a cofactor for TET enzymes involved in DNA demethylation and epigenetic regulation. Mutations in TET2 are common drivers of leukemia. Preclinical studies suggest that VitC may delay leukemia progression. This study aimed to evaluate the biological...

KDM6A loss enhances oxidative phosphorylation uncovering tissue-level convergent evolution

Abstract The tumor suppressor KDM6A / UTX , a histone demethylase and a 2-oxoglutarate-dependent dioxygenase, is frequently lost in many cancer types. We show that KDM6A loss pervasively activates oxidative phosphorylation in several solid tumors, generating a pseudo-hyperoxic en...

Cardiolipin deficiency disrupts electron transport chain and drives steatohepatitis

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive disorder marked by lipid accumulation, leading to metabolic dysfunction-associated steatohepatitis (MASH). A key feature of the transition to MASH involves oxidative stress resulting from defects in...

Starve-Feed Cycles Direct Quiescence to Proliferation Transitions in Drosophila Follicle Stem Cells via Transcriptional Regulation

Stem cell quiescence is a reversible state in which cells temporarily exit the cell cycle but remain poised to re-enter, on cue. Robust protection of the balance between stem cell quiescence and proliferation (Q->P) is critical for long-term tissue health. Proliferation without p...

Histone modification cross talk between a host and pathogen

ABSTRACT Bacterial pathogens modulate host cell physiology by secreting effector proteins that rewire host signaling pathways. A subset of these effectors directly modify host chromatin to reprogram gene expression and promote infection. While these enzymes are thought to functio...

Cardiac Implantable Electronic Device Infection: Nationwide Trends in Extraction Utilization and In‐Hospital Outcomes

INTRODUCTION: Contemporary, real-world adherence to guideline-directed transvenous cardiac implantable electronic device (CIED) extraction for patients with CIED infections in the US remains incompletely characterized. As such, we sought to evaluate national trends in CIED extrac...

A compendium of next-generation patient-derived models for diverse cancers

Abstract The development of new therapeutics and the validation of pathogenetic cancer mechanisms require representative laboratory models 1,2 . However, existing collections represent only a fraction of the diversity observed in human cancer 2–4 . Recent technologies have enable...