Publications by Year: 2026

Aberrant activation of NF-κB transcription factors is a hallmark of human lymphomas. Most lymphoma-intrinsic as well as microenvironment-induced NF-κB activation occurs upstream of the key kinase IKK2, therefore affecting additional pathways. Here, we show that canonical NF-κB signaling in mouse B cells, induced through the expression of one or two copies of a constitutively active IKK2 variant, dose-dependently drives lymphomagenesis. The observed phenotype and stereotypic B cell receptor clonality resemble human small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL). Stronger IKK2 signaling drives early B1a cell expansion and uniform SLL/CLL-like lymphomagenesis, while intermediate signals cause more heterogeneous malignancies. Mechanistically, constitutive IKK2 signals provide a profound cell-intrinsic competitive advantage to B1a cells and dose-dependently synergize with TCL1 overexpression in driving aggressive CLL. Further, strong constitutive NF-κB activation overcomes critical microenvironmental dependencies of TCL1-driven lymphomas. Our findings establish canonical NF-κB as an oncogenic driver in lymphoma and reveal reduced microenvironment dependency as a key NF-κB-mediated mechanism, thus highlighting its therapeutic relevance.

DNA origami holds great potential for advancing therapeutics, but the lack of methods for the precise assessment of structural integrity in vivo prevents its translation. Here we introduce proximity ligation assay for structural tracking and integrity quantification (PLASTIQ) for resolving origami structural integrity with only 1 µl of blood sample and with a detection limit of 0.01 fM. Through PLASTIQ, we could observe and quantify the dynamics of DNA origami degradation during blood circulation and evaluate the effectiveness of PEGylation for slowing this process in a murine model. Additionally, by using a double-layered barrel-like origami structure, we found distinct degradation kinetics of DNA helices depending on their specific location, revealing the slower degradation of internal helices compared with the outer ones. Our results suggest that PLASTIQ offers a quantitative approach for assessing DNA origami integrity in vivo by longitudinal sampling, providing dynamic pharmaceutical-level insights for accelerating the development of DNA-nanostructure-based therapeutic molecules and drugs.

Chronic inflammation promotes aging and age-associated diseases. While metabolic interventions can modulate inflammation, how metabolism and inflammation are connected remains unclear. Cytoplasmic chromatin fragments (CCFs) drive chronic inflammation through the cGAS-STING pathway in senescence and aging. However, CCFs are larger than nuclear pores, and how they translocate from the nucleus to the cytoplasm remains uncharacterized. Here we report that chromatin fragments exit the nucleus via nuclear egress, a membrane trafficking process that shuttles large complexes across the nuclear envelope. Inactivating critical nuclear egress proteins, the ESCRT-III or Torsin complex, traps chromatin fragments at the nuclear membrane and suppresses cGAS-STING activation and senescence-associated inflammation. Glucose limitation or metformin inhibits CCF formation through AMPK-dependent phosphorylation and autophagic degradation of ALIX, an ESCRT-III component. In aged mice, metformin reduces ALIX, CCFs, and cGAS-mediated inflammation in the intestine. Our study identifies a mechanism linking metabolism and inflammation and suggests targeting the nuclear egress of chromatin fragments as a strategy to suppress age-associated inflammation.

Adult, symptomatic Chiari malformation Type I (CMI) is a painful, often debilitating, neurological condition which is defined by the herniation, or extension, of the cerebellar tonsils below the skull. Research has shown that Chiari patients on average exhibit a number of anatomical variations, or morphometric differences, from healthy controls in the cranio-vertebral region; however the potential contribution of these differences to CMI's pathophysiology is not clear. This case-control study looked at nine representative morphometric measures (MM) in 432 adult, female CMI subjects and 148 adult, female controls. Each measure was dichotomized at three increasing distances from the control mean to represent exposures in an odds ratio analysis with CMI as the outcome. In addition, logistic regression modeling was used to determine the overall predictive ability of the MMs. Finally, disease severity was compared across three CMI subgroups with varying degrees of morphometric severity. We found that a reduced fastigium height demonstrated the largest increase in both crude and adjusted odds ratios at every level with an exposure-response pattern. Logistic regression correctly identified 87% of the CMI subjects as CMI based on the MMs. On average, CMI subjects had more than 3 MMs that were at least one standard deviation from the control mean, but there was no association between morphological and disease severity. These results suggest that further studies into anatomical variations such as fastigium height in CMI patients are warranted.

South Asians experience disproportionately elevated cardiometabolic disease risk yet remain underrepresented in genomic research. The OurHealth Study builds a digital biobank of US South Asian adults, integrating remote surveys, mailed biospecimens for sequencing, and electronic health record sharing to identify genetic and non-genetic drivers of cardiometabolic disease. By pairing remote participation with culturally tailored outreach, OurHealth enhances accessibility, supports granular phenotyping, and addresses logistical barriers to genomic research inclusion.

PURPOSE: Intimate partner violence is a pervasive issue deeply affecting public health, and its escalation during the COVID-19 pandemic has raised serious concerns. While the escalating impact of intimate partner violence during the COVID-19 pandemic has been widely acknowledged, there remains a need for a comprehensive systematic review that synthesizes existing literature. This review seeks to address this gap by providing an inclusive assessment of the global landscape of intimate partner violence during and after the pandemic, thereby informing more effective prevention and intervention strategies.

METHODS: A systematic literature search was conducted on PubMed, Google Scholar, and Scopus databases using different MeSH terms. A total of 445 relevant articles were identified initially, and after thorough screening, 54 articles were included in the review.

RESULTS: The lockdown had several negative consequences, including job losses, economic vulnerability, and health issues due to prolonged loneliness and uncertainty. An increase in emergency hotline or Women's Helpline calls was observed. Globally, intimate partner violence surged during the lockdown and persisted into 2023, causing severe and lasting health, psychological, and reproductive consequences for victims. Our results showed that COVID-19 increased the risk of partner violence: post-COVID intimate partner violence risk greater than pre-COVID risk (0.33 vs. 0.28, respectively).

CONCLUSION: Although COVID-19 increased the risk of intimate partner violence, this review also stresses a high global prevalence of intimate partner violence, not restricted to the pandemic and lockdowns. To prevent partner violence and reduce long-lasting severe health, psychological, and reproductive consequences of partner violence, broad cooperation between governments, communities, health professionals, and the media is necessary.

Visceral leishmaniasis (VL), caused by Leishmania infantum, is a major public health concern in Brazil, with domestic dogs as key reservoirs. Accurate diagnosis is crucial, but current tools like rK39 have limited sensitivity and regional variability. This study evaluated three recombinant kinase antigens-Repressor of Differentiation Kinase 2 (RDK2), Aurora I-related kinase (LdAIRK), and Activated C Kinase Receptor (LACK)derived from Leishmania donovani for their diagnostic potential in canine VL (CanL) and RDK2 in human VL. These antigens were selected based on amastigote-stage expression, conservation among virulent strains, and low homology with host proteins or co-endemic pathogens. Using computational prediction, and immunoproteomics, antigens were expressed and further validated via ELISA and dipstick assays. Serum samples from humans (VL, n = 40; controls, n = 19) and dogs (CanL, n = 36; controls, n = 36) were collected in Teresina, Brazil. RDK2 showed (90% sensitivity, 78.95% specificity) for human VL, while LdAIRK showed the highest diagnostic accuracy for CanL (88.89%, 97.22%), followed by LACK and RDK2. Dipstick tests confirmed these findings, offering rapid, field-friendly alternatives and demonstrating enhanced performance compared to two reference rK39 tests, pending broader comparative validation. LdAIRK emerged as a promising diagnostic marker for CanL, with the potential to enhance VL control in endemic regions.

Evidence suggests that cancer-related accelerated aging contributes to an earlier onset of chronic diseases; persistent symptoms; and decrements in patients' quality of life. This review presents the Multifactorial Model of Cancer-related Accelerated Aging (MMCRAA), a conceptual framework that is grounded in Life Course Theory and supported by empiric evidence. The model includes six inter-related concepts: person, behavioral, biological, treatment, symptom, and life course factors. The MMCRAA can be used by clinicians and researchers to identify patients at increased risk for cancer-related accelerated aging; guide personalized treatment planning; and inform the development of interventions and research.

Subdominant B-cell immune responses to conserved epitopes are major obstacles in eliciting broadly neutralizing antibodies (bnAbs) against HIV-1 through natural infection or vaccination. Although the sequence conserved membrane proximal external region (MPER) of HIV-1 gp41 is partially occluded on the virion surface, epitope-focused immunogens could mitigate access limitations. Here, we found that a MPER/liposome vaccine delivered with a single CD4 T cell helper epitope results in a post-priming response hierarchy, eliciting low-affinity MPER-specific B cells. Heterologous boosting, however, promotes MPER-specific B cell clonal expansion and enhances plasma antibody functionality. This improvement is associated with increased B-cell affinity for MPER and reduced competition from B cells targeting the helper epitope. While helper peptide co-delivery increases the affinity of serum antibodies, the outcome of subsequent MPER antibody responses is shaped by the priming antigen. Our results offer insights into heterologous immunization strategies to potentiate subdominant B cell responses against frequently mutating viruses.