At the 10th Annual RNA Symposium hosted by the Harvard Initiative for RNA Medicine (HiRM), Dr. Zhaoji Liu presented new findings from Drs. Gerburg Wulf and Jan Heng’s research group at Beth Israel Deaconess Medical Center. They discovered that elevated microRNA 362-3p in plasma was associated with cisplatin response in BRCA-mutated, HER2-negative breast cancer patients. Their findings utilized data from the INFORM phase II clinical trial (NCT01670500; PI: Dr Nadine Tung), which focused on predicting treatment response in this challenging breast cancer subtype.

 

The INFORM trial included 118 patients with BRCA1/2 mutations and HER2-negative tumors across 13 U.S. hospitals. Participants were randomized to receive either cisplatin or standard anthracycline-based chemotherapy. Pre-treatment plasma samples were screened for over 350 microRNAs using the ID3EAL™ Cancer miRNA Panel. Notably, miR-362-3p emerged as a key biomarker, with its elevated plasma levels significantly correlating with improved outcomes (complete pathological response and minimal residual disease) only in patients treated with cisplatin.

 

As researchers continue to validate these findings in vivo, miR-362-3p is a promising target for both prognostic testing and personalized treatment in BRCA-driven breast cancer. This study not only suggests that miRNA levels can influence a tumor’s response to chemotherapy but also offers hope for more personalized and effective treatments.

 

Download a copy of the poster:

Heng HiRM 2024 RNASym Poster INFORM miRNA – 04172025

 

Keywords: miRNA, cyclophosphamide (AC), neoadjuvant cisplatin monotherapy, estrogen receptor (ER), complete pathological response (pCR; i.e., cancer-free), residual cancer burden (RCB), platinum-containing neoadjuvant regimen (cisplatin), tumor biopsies, triple-negative breast tumors, The Cancer Genome Atlas (TCGA), cancer, BRCA-related breast cancer, MiRXES, ID3EAL™ Cancer miRNA Panel.

 

Poster presented at the 2025 AACR meeting in Chicago

“Circulating Epstein-Barr Virus microRNAs Associated with Hodgkin Lymphoma Prognosis”

At the 2025 AACR Annual Meeting in Chicago, we presented findings on the potential of Epstein-Barr Virus (EBV) microRNAs as non-invasive biomarkers for Hodgkin Lymphoma (HL) prognosis. This research was conducted through a collaborative effort between Estelle Verburgh (University of Cape Town), Katherine Antel (Medical University of South Carolina), and the Initiative for RNA Medicine at Harvard Medical School. Plasma samples were collected from HL patients in Cape Town, South Africa, a region with a high prevalence of HIV and tuberculosis. From these samples, 42 EBV-encoded microRNAs were profiled using the ID3EAL™ qPCR EBV miRNA panel.

Surprisingly, miRNA expression correlated with disease severity but not with EBV or HIV status. Notable associations included miR-BART17-3p with disease stage and miR-BART2-5p with the International Prognostic Score. Four miRNAs were identified as key indicators of B-symptoms, which correlated with HL progression.

These results highlight the potential of EBV miRNAs as prognostic markers, though larger cohorts are needed for validation. Continued exploration could yield valuable insights into Hodgkin lymphoma biology and therapeutic strategies.

Keywords: AACR, RNA Medicine, Epstein-Barr Virus (EBV), International Prognostic Score, Hodgkin Lymphoma (HL)

 

Download it here:

Lee EBV Poster AACR 2025 FINAL

 

Poster Summary:

AACR2025_Mirxes_Speaker_Slides EBV-HL

 

 

Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is the leading cause of dementia globally, affecting over 32 million people as of 2023. Characterized by cognitive decline, memory deficits, and behavioral changes, AD is marked by the accumulation of amyloid-β plaques and neurofibrillary tangles in the brain’s gray matter. Aging is a significant risk factor, particularly in the prefrontal cortex (PFC), a region critical for higher cognitive functions. Despite years of research, the molecular mechanisms distinguishing AD from normal aging remain elusive. In a recently published study titled “Stereo-seq of the prefrontal cortex in aging and Alzheimer’s disease,” researchers at Tulane University in the Deming Department of Medicine performed the first subcellular-resolution spatial transcriptome atlas of the PFC from Alzheimer’s disease patients. The researchers published their findings in the January 8th, 2025, issue of Nature Communications.

Background and Objectives

The researchers aimed to uncover the molecular mechanisms underlying aging-related susceptibility to AD by comparing transcriptomes from the PFC of six male AD patients and six age-matched controls. Previous studies, such as those using 10X Visium, revealed AD-associated gene expression changes but lacked the spatial resolution to dissect single-cell interactions. By employing Stereo-seq, this study sought to:

  1. Identify transcriptional differences across PFC layers.
  2. Characterize cell-cell interactions influencing AD pathology.
  3. Highlight potential therapeutic targets.

Methodology

Using Stereo-seq, the team analyzed cryosections of PFC tissue, focusing on seven predominant cell types: astrocytes (Ast), excitatory neurons (Ex), inhibitory neurons (Inh), microglia (Mic), endothelial cells (End), oligodendrocyte progenitor cells (Opc), and oligodendrocytes (Oli). By aligning transcriptional data with spatial maps, they generated a detailed atlas revealing layer-specific and cell-type-specific alterations in AD.

 

From Gong Y. et al. Nature Communications 2025

Key Findings

  1. Disruption of Laminar Structure The study identified significant structural changes in PFC layers, particularly in advanced AD cases. Layers II-VI showed marked thinning and transcriptional disruptions, highlighting the vulnerability of these regions to neurodegeneration.
  2. Gene Modules Linked to Neuroprotection
    • Immune Response and Inflammation Regulation: Genes regulating immune activity were upregulated in stressed neurons and glial cells, emphasizing the role of inflammation in AD progression.
    • Protein Homeostasis: Modules governing protein degradation—crucial for clearing amyloid-β and tau aggregates—were significantly downregulated.
    • Synaptic Function: Genes involved in synaptic transmission and plasticity showed decreased expression, correlating with cognitive decline in AD.
  3. ZNF460: A Potential Therapeutic Target The transcription factor ZNF460 was identified as a regulator of the aforementioned gene modules. Its downregulation in AD suggests it could be a promising therapeutic target for restoring neuroprotective pathways.
  4. Spatial Patterns of Stress Response Stressed neurons exhibited elevated mitochondrial gene expression, correlating with neuroinflammation and oxidative stress. Adjacent glial cells—particularly astrocytes—showed transcriptional changes supporting neuronal survival and amyloid-β clearance.
  5. Altered Cell-Cell Communication Communication networks between cortical layers, mediated by ligand-receptor interactions, deteriorated with AD progression. Notably, the loss of glutamate signaling in excitatory neurons underscored synaptic dysfunction as a hallmark of AD.

 

Implications for Alzheimer’s Research

This study provides critical insights into the spatial and molecular dynamics of AD in the PFC:

  • High-Resolution Mapping: By identifying transcriptional changes at single-cell resolution, researchers can pinpoint early markers of AD pathology.
  • Targeted Therapies: Discovering regulators like ZNF460 opens avenues for precision medicine aimed at restoring neuronal health.
  • Enhanced Understanding of Disease Progression: The spatial context of gene expression reveals how cellular interactions evolve in response to AD pathology, offering a more holistic view of the disease.

Expanding Access to Stereo-seq Technology

The accessibility of Stereo-seq services is crucial for advancing research. MiRXES, a leading genomics and bioinformatics service provider, was the first independent U.S.-based organization to offer Stereo-seq. In January 2025, MiRXES expanded its capabilities to include formalin-fixed, paraffin-embedded (FFPE) tissue, a common medium used for archived samples. This advancement significantly broadens the scope of AD research by enabling the study of historical tissue collections.

Conclusion

Integrating Stereo-seq into Alzheimer’s research marks a new era of discovery, offering unprecedented clarity into the disease’s cellular and spatial dynamics. By bridging the gap between molecular profiling and spatial context, this technology holds the potential to unravel the complexities of neurodegeneration and pave the way for innovative therapies. As accessibility to Stereo-seq services grows, the scientific community stands on the cusp of breakthroughs that could redefine our understanding and treatment of Alzheimer’s disease.

Keywords and abbreviations: Stereo-seq, spatial transcriptomics, Alzheimer’s Disease (AD), prefrontal Cortex (PFC), neurodegeneration, astrocytes (Ast), excitatory neurons (Ex), inhibitory neurons (Inh), microglia (Mic), endothelial cells (End), oligodendrocyte progenitor cells (Opc), oligodendrocytes (Oli), formalin-fixed paraffin-embedded (FFPE) tissue, Visium, dementia, genomics

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