Scientific Writer @ CENOS St. Jude Children's Research Hospital

A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies Pineoblastoma is an aggressive childhood brain cancer. Using single-cell transcriptomics of patient tumors, developing pineal gland, and engineered models, Gudenas et al. identify pinealocyte progenit...

Pineoblastoma is an aggressive brain tumor with few treatment options. Today in Cancer Cell, the Northcott lab defined its developmental origins, analyzed the largest cohort to date, and introduced 5 new models to uncover shared vulnerabilities across pediatric CNS tumors. tinyurl.com/mse9427s

M-PACT leverages cell-free DNA methylomes to achieve robust classification of pediatric brain tumors - Nature Cancer Smith et al. present M-PACT, a deep neural network leveraging low-input cell-free DNA methylation profiles to achieve robust classification of pediatric brain tumors and enable cellular deconvolution ...

⭐Technical Report out today at Nature Cancer

The deep neural network M-PACT uses low-input cell-free DNA methylation profiles to classify pediatric brain tumors
@doctorpauln77.bsky.social

www.nature.com/articles/s43...

Classifying pediatric brain tumors by liquid biopsy using artificial intelligence See how M-PACT, an AI-powered algorithm can sift through ctDNA in cerebrospinal fluid and molecularly classify tumors based on their DNA methylation pattern

The Northcott group introduced M-PACT, a next-generation AI classifier using DNA methylation from liquid biopsies.
M-PACT overcomes challenges arising from low levels of DNA for accurate classification and monitoring of tumor microenvironment and evolution. #NatureCancer
tinyurl.com/36duu9az

The MB-meta Portal--an online tool for exploring predicted survival based on clinical and molecular features--helps guide decisions and supports further research into new treatment strategies. Try it here: proteinpaint.stjude.org/mbportal/ #PediatricCancer #BrainTumorResearch

Data-driven risk stratification guides childhood brain tumor treatment, reducing side effects Find how St. Jude researchers discovered a new way to group patients with medulloblastoma, which could lead to major reduction in treatment-related toxicity.

Scientists at St. Jude published the largest analysis of #medulloblastoma treatment from ~900 patients. By harmonizing clinical & molecular data, they identified new risk groups—enabling more precise, less toxic therapies for kids. ow.ly/XtYs50Xn8cF 🧠✨

We are pleased to welcome Dr. Olivier Ayrault from Institut Curie as a guest speaker for the CENOS-NBTP seminar series presenting "Causal Multi-omics Integration Reveals Metabolic Dependencies in Human Medulloblastoma".

MOADE: a multimodal autoencoder for dissociating bulk multi-omics data - Genome Biology In single cell biology, the complexity of tissues may hinder lineage cell mapping or tumor microenvironment decomposition, requiring digital dissociation of bulk tissues. Many deconvolution methods focus on transcriptomic assay, not easily applicable to other omics due to ambiguous cell markers and reference-to-target difference. Here, we present MOADE, a multimodal autoencoder pipeline linking multi-dimensional features to jointly predict personalized multi-omic profiles and cellular compositions, using pseudo-bulk data constructed by internal non-transcriptomic reference and external scRNA-seq data. MOADE is evaluated through rigorous simulation experiments and real multi-omic data from multiple tissue types, outperforming nine deconvolution pipelines with superior generalizability and fidelity.

(2/2) Now published in Genome Biology, this tool demonstrated improved performance compared to 9 existing pipelines: tinyurl.com/munzep9x
MOADE is available on GitHub: github.com/jsuncompubio...

A new computational method to separate bulk multi-omics data has been developed in collaboration between Qian Li and Paul Northcott’s lab. MOADE can predict cell types and generate personalized molecular profiles for analyzing complex tissues and tumors. (1/2)

Alisha Kardian, graduate student in the Mack lab, is the 2025 recipient for the prestigious Schweisguth Prize awarded for the best scientific article by a trainee in pediatric oncology. Congratulations on this outstanding achievement! siop-online.org/schweisguth-...

Congratulations to co-first authors Dr. Amir Arabzade and Srinidhi Varadharajan, Dr. Stephan Mack in DNB/CENOS, and Dr. Richard Kriwacki in Structural Biology on the publication of your work!

Synthetic ZFTA fusions pinpoint disordered protein domain acquisition as a mechanism of brain tumorigenesis - Nature Cell Biology Arabzade, Shirnekhi, Varadharajan, Ippagunta and colleagues show that the zinc finger translocation-associated (ZFTA) fusion oncoproteins gain intrinsically disordered regions, inducing nuclear conden...

Droplet-like formation of nuclear condensates underlies how a fusion oncoprotein disrupts gene expression in a form of pediatric cancer. This study spanning disease biology, molecular genetics, and biophysics was published today in Nature Cell Biology. www.nature.com/articles/s41...

Research implicates biomolecular condensates in a type of childhood brain cancer Discover research showing that small disordered regions of a fusion protein creates droplets called condensates that are essential to ependymoma development.

Ependymoma, the third most common childhood brain tumor, has seen little therapeutic progress in 30+ years. New findings reveal how the ZFTA–RELA fusion protein drives tumor formation via condensates. ow.ly/fg4r50WMPZJ

The Mack lab congratulates Amelia Hancock, a student from the ‪@uniofbath.bsky.social‬ exchange program, for her fantastic presentation on the work conducted during her year-long rotation. She has been an awesome part of the lab and will be greatly missed!

Dr. Stephen Mack, Associate Member of DNB & CENOS, is presenting “Deciphering the molecular and cellular basis of fusion driven ependymoma to uncover novel therapies” for the virtual Science of Childhood Cancer Lecture Aug 21. stjude.org/socc

We are excited to kick off this season of SOCC with a milestone: our 150th lecture. Join us every Thursday, from 8/14 to 11/20, at 12 PM CT / 1 PM ET for an engaging and interactive 15-week virtual lecture series.

The Baker lab had a fantastic experience mentoring POE intern Ethan Wunibald through the summer. He did an excellent job learning an array of techniques in the lab and presenting his findings. We look forward to seeing what he accomplishes next!

The Northcott lab is proud of High School Research Immersion Program student Catherine Carney for her summer research project poster. Your hard work and boundless curiosity was clear in your findings and way you answered tough questions. We know you have a bright future ahead!

CAR T–cell therapy shows promise for ependymoma though barriers remain Find out how B7-H3-targted chimeric antigen receptor (CAR) T cells successfully killed ependymoma tumors in some models but still faced resistance in others.

A recent study testing CAR-T immunotherapy for ependymoma identified treatment promise and new questions to understand how the immune response can influence treatment response. www.stjude.org/research/pro...

We appreciate the care and professionalism of the editorial team and referees who oversaw this process. Our Matters Arising highlights the importance of scientific rigor, careful quality control, and cross-validation when handling high-dimensional sequencing datasets.

Lack of evidence for the transitional cerebellar progenitor - Nature Nature - Lack of evidence for the transitional cerebellar progenitor

which we communicated to both the lead corresponding author and the journal. The original paper, along with our re-analysis of this cerebellar dataset, underwent extensive peer review and is now available as a Matters Arising article in Nature. tinyurl.com/2534fr9e

Lack of evidence for the transitional cerebellar progenitor - Nature Nature - Lack of evidence for the transitional cerebellar progenitor

The Northcott lab conducted an extensive re-analysis of a single-cell transcriptional atlas of human cerebellar development originally published in 2022. During this process, we identified significant concerns related to data integrity and interpretation,

Graduate Student Sanya Mehta and Postdoc Siri Ippagunta tested CAR T-cell immunotherapy in ependymoma models. This collaboration between the Stephen Mack and Giedre Krenciute labs examines how the immune system responds to CAR-T cells and mediates treatment efficacy. doi.org/10.1158/1078...

A deeper understanding of how cells organize themselves is changing the way we think about neurological diseases. At St. Jude, researchers are studying biomolecular condensates—droplets that organize proteins, RNA and DNA—to uncover new treatment strategies. ow.ly/tzpp50WbzjK

Congratulations to the Northcott team making the cover of Cancer Cell for their work demonstrating how inherited ELP1 variants confer risk for SHH #medulloblastoma! tinyurl.com/39p365ae

Isocitrate dehydrogenase 1 primes group-3 medulloblastomas for cuproptosis Dang et al. report that group-3 medulloblastomas (MBs) show c-MYC-driven high DLAT expression. In these tumors, wild-type IDH1 epigenetically regulates c-MYC, and inhibiting IDH1 lowers c-MYC and DLAT expression. Further, DLAT sensitizes group-3 MBs to cuproptosis. Notably, the copper ionophore elesclomol is toxic to multiple group-3 MB models, underscoring its therapeutic potential.

Online Now: Isocitrate dehydrogenase 1 primes group-3 medulloblastomas for cuproptosis

Genetic modeling of ELP1-associated Sonic hedgehog medulloblastoma identifies MDM2 as a selective therapeutic target Elp1 heterozygous LOF mutations in Sonic hedgehog medulloblastoma (MB) elevate transformation risk in granule neuron precursors through stalled differentiation, DNA replication stress, genomic instability, and accelerated cell cycle. Pharmacological restoration of p53 signaling in ELP1-deficient tumor cells suppresses tumor growth and represents a potential therapeutic opportunity.

Online Now: Genetic modeling of ELP1-associated Sonic hedgehog medulloblastoma identifies MDM2 as a selective therapeutic target

Study reveals targetable mechanism behind high-risk predisposition gene in pediatric medulloblastoma Uncover how ELP1 gene defects drive pediatric brain cancer—and learn how that revealed MDM2 inhibition as a targeted therapy to restore tumor suppressor p53.

The Northcott lab identified inherited ELP1 loss increases risk for SHH #medulloblastoma through stalled differentiation, DNA replication stress, genomic instability, and accelerated cell cycle. Restoring p53 signaling was found to have therapeutic potential.
tinyurl.com/5355xy6t

Congratulations to the Northcott lab for 10 years at St Jude! Thank you to the Mack lab for joining as we celebrate this important milestone!

We are pleased to welcome Dr. Sameer Agnihotri from the University of Pittsburgh as a guest speaker for the CENOS-NBTP seminar series presenting "Microenvironmental, Epitranscriptomic, and Chromosomal Engineering Approaches to Uncover Translational Targets for Gliomas".