About the Mack Lab

Pediatric brain tumors are the leading cause of cancer-associated death in children. Understanding the origins and mechanisms of these diseases is central to developing new treatment approaches. Our lab is interested in interrogating the epigenetic and transcriptional landscape of pediatric brain tumors and translating these findings into clinical evaluation. We hope to improve our understanding of general principles of cancer, while creating rational and effective solutions for our patient populations.

Science Team

The Team

The Mack Lab has a multi-disciplinary team of molecular biologists, clinician scientists and computational experts leveraging complex data and faithful model systems to understand pediatric brain tumors.

Our research summary

Our lab is interested in a variety of pediatric brain tumors, and we are committed to pursuing biologically relevant and actionable targets in a comprehensive preclinical pipeline. From fundamental mechanisms to clinical evaluation, we use state-of-the-art technologies to ask critical questions related to disease origin, development, and response to therapy.

Exploring fundamental mechanisms of pediatric brain tumors

Epigenetic regulators and fusion proteins have been identified as drivers in diseases like ependymoma and high-grade glioma. We are interested in deciphering the resulting transcriptional landscape and chromatin architecture, defining the role of novel proteins, and understanding their function. In addition to identifying how these drivers shape transcriptional epigenetic programs, we also explore the cell types that facilitate these neoplastic programs. These challenges are tackled using modern bulk and single cell sequencing approaches to characterize transcriptional programs and epigenetic landscapes.

Our team uses in utero electroporation to transform cells during development to define both the drivers, and the cells, that give rise to pediatric brain tumors. We have a particular interest in the mechanisms of K27M-driven high-grade gliomas and RELA fusion ependymoma. Leveraging animal models of these diseases, we aim to understand the function of drivers and the impact of landscape changes on disease mechanisms in vivo. Recent work suggests that RELA fusion proteins interact with transcriptional phase condensates to drive oncogenesis. This has stimulated a new project pipeline to explore phase separation and its role in tumorigenesis.

Mack Lab

Translating molecular findings to clinical application

Recognizing the need for new targeted therapies, our team has developed an extensive network of collaborators to design and evaluate interventions. We interface with clinicians to determine clinical priorities and opportunities, and design robust preclinical studies to inform future development. Ongoing projects range from translating epigenetic inhibitors to identifying cell surface antigens and building CAR-T based therapies. We are also exploring how modifying the epigenetic landscape impacts tumor microenvironment, creating potential for layered or combination therapeutic approaches. We’ve generated one of the largest sets of ependymoma models and are beginning to evaluate strategies to explore tumor dependencies with functional in vivo screens.

Selected Publications

Contact us

Stephen Mack, PhD
Associate Member, Developmental Neurobiology

Department of Developmental Neurobiology
MS 323, Room M3405
St. Jude Children's Research Hospital

262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
(901) 595-2972 stephen.mack@stjude.org

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262 Danny Thomas Place
Memphis, TN, 38105-3678 USA