Haematologica: IGF2BP3 inhibition: another home run for RNA-binding protein targeting in hematological malignancies (Penalva)

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Luiz O.F. Penalva

RNA-binding proteins (RBPs) are critical regulators of gene expression, aNecting RNA
processing till translation. More than 1,500 proteins have been catalogued as RBPs in the
human genome. 1 RBPs are very diverse in respect to structure, characteristic of RNA
binding domain and function. In fact, RBPs are notoriously multi-functional with some of
them showing great target diversity and ability to bind both mRNA and diNerent types of
ncRNAs. By orchestrating the expression of gene networks, RBPs modulate complex
biological processes such as diNerentiation and cell fate decisions. 2 In cancer, aberrant
expression of RBPs has been reported over the years in multiple tumor solid tumors and
hematological malignancies. Their subsequent molecular characterization and genomic
analysis led to the identification of “oncogenic” RBPs and provided maps of their target
genes. Despite their relevance and established role in tumorigenesis, RBPs have not been
fully explored as candidate targets in cancer therapy.

 

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GCCRI &10x Genomics Presents: Spatial GEX Sample Prep Seminar (Xenium & Visium Applications)

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The Genome Sequencing Facility (GSF) at the Greehey Children’s Cancer Research Institute (GCCRI), serving as the Next Generation Sequencing Shared Resource (NGSSR) of the Mays Cancer Center, is pleased to invite you to a Spatial Transcriptomics Sample Preparation Seminar hosted in collaboration with 10x Genomics.

Spatial transcriptomics (ST) enables measurement of gene expression within the precise spatial context of tissue architecture. By preserving spatial information, ST provides powerful insight into cellular heterogeneity, cell–cell interactions, molecular gradients, and gene signatures associated with pathological features.

Current ST technologies generally fall into two categories:

  • Sequencing-based ST (sST), such as Visium HD, where tissue sections are placed on spatially barcoded substrates. Transcripts are captured, sequenced, and computationally mapped back to their original locations to generate whole-transcriptome spatial maps.
  • Imaging-based ST (iST), such as Xenium, which uses multiplexed fluorescence in situ hybridization (FISH) approaches to visualize and identify transcripts directly in tissue with single-molecule resolution across iterative imaging cycles.

These complementary platforms often serve different experimental goals. Visium HD is commonly used as a discovery tool due to its whole-transcriptome coverage, while Xenium is well suited for hypothesis-driven studies when specific targets or pathways—such as those in the tumor microenvironment—are already defined.

A critical determinant of success in any spatial transcriptomics project is high-quality tissue slide preparation. Recognizing this challenge, we have organized this seminar to provide practical guidance and support for optimal sample preparation.

During the seminar, Dr. Micah Castillo from 10x Genomics will present best practices for tissue slide preparation for both Visium HD and Xenium platforms. This session offers a valuable opportunity to learn how to effectively incorporate advanced spatial transcriptomics technologies into your research.

We warmly encourage investigators, postdoctoral fellows, graduate students, and research staff to attend. Please click the attache flyer to register seminar.

SIOP 2026: Where Global Collaboration Meets Texas Hospitality

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Cure for more. Care for all. Together in San Antonio. 🌍🤠

The journey to SIOP 2026 (Sept 15-18) is officially underway, and we are preparing a welcome as big as Texas itself! As the only global multidisciplinary society dedicated entirely to pediatric and adolescent cancer, our mission is driven by one core belief: No child should die of cancer.

A Bridge Across the Americas & Beyond 🤝

Collaboration is the heartbeat of SIOP. We are thrilled to highlight the unique, welcoming spirit of this year’s meeting, which begins even before the main Congress:

  • The SIOP North America-SLAOP Pre-meeting: A powerful collaboration between North and Latin American experts to bridge gaps in care and research.
  • Affiliated Excellence: We are proud to host our partners from IPSO (Surgeons), PROS (Radiation Oncologists), and Childhood Cancer International (CCI), ensuring the voices of survivors and parents are central to our work.

Innovating for the Future: SIOP NEXT & More 🌟

The legacy of our society lives in our growth. We are continuing the successful SIOP NEXT program—a dedicated platform for networking, education, and excellence for the next generation of basic and translational scientific leaders.

One Mission, Every Discipline

Whether you are a seasoned expert or a first-time attendee, there is a community waiting for you in San Antonio:

🔬 Basic Scientists & Translational Researchers

👩‍⚕️ Nurses & Allied Health Professionals

🩺 Clinicians & Young SIOP members

🎗️ Advocates, Parents, & Survivors

It happens at the intersection of surgery and science, nursing and nutrition, advocacy and advanced therapeutics, and medicine and mentorship.

Join us in San Antonio!

Experience the world-famous River Walk, the deep history of the Alamo, and the collaborative energy of a global community united for a cure.

📅 Abstract Submission Deadline: March 17, 2026

🔗 Submit your work and join the community: SIOP 2026 Link

Who is joining us in the Lone Star State? Share with a colleague or a mentee who needs to be part of this mission!

Learn More @  siop-congress.org/

BioRxiv: High-throughput mapping of 6,888 RAD51D variants identifies distinct biochemical functions needed for homologous recombination and olaparib response (Sung)

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Kristie E. Darrah, Shelby L. Hemker, Yashpal Rawal, Noah J. Goff, Phoebe Parker, Gayatri Ganesan, Caleb M. Stratton, Katherine Oppenheimer, Ella Roberts, Elena Glick, Nicole Banks, Arjun Kumar, Silvia Casadei, Matthew W. Snyder, Katherine Nathanson, Susan M. Domchek, Lea M. Starita, Shaun K. Olsen, Patrick Sung, Jacob O. Kitzman, Kara A. Bernstein

Summary

The tumor suppressor RAD51D is essential for homologous recombination (HR). Pathogenic variants in RAD51D are associated with breast and ovarian cancers. However, most clinical missense variants are of unknown significance. We performed a multiplex assay of variant effect to test 6,888 RAD51D coding variants for loss-of-function. The resulting variant-to-function map perfectly separates known pathogenic and benign variants and is validated by orthogonal HR and biochemical assays across 70 clinical variants. Our screen shows that variants in the DNA-binding or ATPase core most severely compromise HR, and we identify the RAD51D-RAD51C interface within the BCDX2 complex as essential for regulating its ATPase activity. We hypothesize that, paradoxically, the primary function of RAD51D is to slow the ATPase activity of BCDX2, thereby allowing sufficient time and space for RAD51 filament assembly. Together, we identify hotspots of deleterious RAD51D variants and uncover the mechanisms by which variants compromise its biochemical functions.

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🚴‍♀️ Register Early & Save—Gear Up Against Kids Cancer Ride

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Don’t miss your chance to save on the Gear Up Against Kids Cancer Bike Ride!
Early‑bird registration is just $50—but only for a limited time. After the early‑bird period ends, the registration fee increases by $20, about the cost of a new pair of cycling gloves.
Register now to:
✅ Lock in the $50 early‑bird rate
✅ Guarantee your Gear Up ’26 event shirt
✅ Support vital childhood cancer research at Greehey CCRI
Time passes quickly — don’t wait—register early and ride for a great cause!
👉 Register today: GearUpAgainstKidsCancer.org
See you on the ride!

Journal of Biological Chemistry: Phosphoregulation of RAD51AP1 function in homology-directed repair (Sung Lab)

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ABSTRACT

Homology-directed DNA repair (HDR) is critical for genome stability and tumor suppression. HDR is initiated by the RAD51 single-stranded (ss)DNA nucleoprotein filament, which conducts a homology search and invades a homologous DNA template, forming a displacement loop (D-loop). The RAD51 filament is assisted in these processes by several proteins. One such protein is RAD51-Associated-Protein 1 (RAD51AP1), which binds DNA and RNA and directly interacts with RAD51. Of note, RAD51AP1 overexpression is associated with poor prognosis in several different cancer types.
Here, we show that RAD51AP1 activity is regulated by phosphorylation. RAD51AP1 bearing S277/282A mutations is more proficient in the stimulation of D-loop formation than wild-type RAD51AP1 or phosphomimetic RAD51AP1-S277/282D. In EMSAs, RAD51AP1 with S277/282A mutations more avidly binds ssDNA, double-stranded (ds)DNA, and the nucleosome core particle than wild-type RAD51AP1 or RAD51AP1-S277/282D. In cells, RAD51AP1-S277/282A confers no rescue of RAD51AP1 deficiency in toxicity tests and DNA replication assays. In contrast, RAD51AP1-S277/282D fully rescues RAD51AP1 deficiency. We provide evidence that RAD51AP1-S277 is a CDK2 target and propose a model in which RAD51AP1-S277/282 phosphorylation ensures RAD51AP1 flexibility for dynamic engagement in consecutive steps of the HDR reaction. Our results provide new mechanistic insights into RAD51AP1 regulation by a CDK.
Keywords
Homology-directed repairRAD51AP1

CDK1/2

cell cycle

DNA binding

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BioMolecules: The PELP1 Pathway and Its Importance in Cancer Treatment (Rao Lab)

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 Ratna K. Vadlamudi

Abstract

Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a proto-oncogene that serves as a nuclear and cytoplasmic scaffolding protein. PELP1 plays a critical role in nuclear receptor signaling, ribosome biogenesis, chromatin modifications, cell cycle progression, non-genomic signaling, and DNA damage response. PELP1 expression is upregulated in a variety of cancers, including breast, ovarian, endometrial, prostate, and liver cancers, and serves as a prognostic factor for poor survival. PELP1’s structural motifs, unique scaffolding function, and oncogenic activity make it a potential target for a range of therapeutic approaches. This review summarizes the most recent advances in PELP1 biology, with a particular focus on the emergent oncogenic functions of PELP1 and its inhibitors for cancer treatment.

Frontiers: Editorial -Antioxidants in Mitigating Oxidative Stress-Induced Damage (Aune Lab)

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  • Marisol Fernandez-Ortiz 1*
  • Ramy K. A. Sayed 2
  • Russel J. Reiter 3

Editorial on the Research Topic: Antioxidants in mitigating oxidative stress-induced damage

Oxidative stress arises from an imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defenses that normally maintain redox homeostasis. When ROS accumulate in excess, they damage lipids, proteins, and nucleic acids, impair mitochondrial function, disrupt signaling networks, and compromise cell viability. Because this redox imbalance contributes to aging and to the pathophysiology of neurodegeneration, organ toxicity, reproductive decline, cancer, and metabolic disorders, there is a pressing need to understand how antioxidant strategies can counteract ROS-induced injury. The Research Topic Antioxidants in Mitigating Oxidative Stress-Induced Damage was established to gather studies that illuminate mechanisms of oxidative damage and explore the protective effects of antioxidants across diverse biological systems. With the full set of contributions now published, this Editorial highlights central findings, thematic insights, and future directions that emerge from this Research Topic.

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Dr. Raushan Kurmasheva’s laboratory has been awarded a $400K NCI SBIR Phase II grant titled “Enhanced overall survival in high-risk pediatric tumors using a novel oral small molecule.”

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Federal Awarding Agency: NIH/NCI

Project Title: Enhanced overall survival in high-risk pediatric tumors using a novel oral small molecule.

Sub PI: Raushan Kurmasheva, PhD

Start: 9/15/25 End: 9/14/27 Amount: $401,844

Project Summary: The research in this NCI-SBIR phase 2 contract focuses on developing a therapeutic for rare pediatric cancers. The original phase 1 contract was for the development of a novel therapy for rhabdomyosarcoma, a rare, aggressive pediatric cancer with poor outcomes. This contract will allow us to complete IND-enabling studies for our drug candidate and to identify additional pediatric cancers that could be included in a Phase 2 clinical trial.

Star Protocols: Transformer and graph variational autoencoder to identify microenvironments: A deep learning protocol for spatial transcriptomics (Chen)

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Highlights

  • Workflow to build spatial objects linking stitched images with transcriptomics data
  • Steps to apply the transformer and GraphVAE for spatial and contextual tissue modeling
  • Guide to merge gene expression and histology data into one spatial framework.
  • Instructions for clustering and deconvolution to map tumor niches at the single-cell level
Summary
We present a transformer and a graph variational autoencoder to identify microenvironments (TG-ME). This computational framework integrates transformer and graph variational autoencoders to dissect spatial niches using spatial transcriptomics and morphological images. This protocol outlines data normalization, spatial transcriptomics integration, morphological feature extraction, and niche profiling. Using deep learning, TG-ME enables robust niche clustering applicable to healthy, tumor, and infected tissues.