John Matthew Maris
University of Pennsylvania · Rehabilitation Medicine
Active 1984–2024
About
John Matthew Maris, M.D., is a Professor of Pediatrics (Oncology) at the University of Pennsylvania's Perelman School of Medicine. He is a member of the Hematology/Oncology Fellowship Committee at Children's Hospital of Philadelphia and serves as Co-Chair of the Genetics, Genomics and Pediatric Diseases Research Affinity Group at the same institution. Dr. Maris holds the Giulio D'Angio Endowed Chair in Neuroblastoma Research and is affiliated with the Abramson Family Cancer Research Institute. His research focuses on neuroblastoma, with significant contributions to understanding the genomic and molecular characteristics of the disease. He has been involved in serial profiling of circulating tumor DNA to identify the evolution of actionable genomic alterations in high-risk neuroblastoma. Dr. Maris has also contributed to preclinical investigations of targeted radiopharmaceutical therapies and the development of novel molecular subgroups and survival predictors in neuroblastoma. His work includes evaluating therapeutic agents and understanding the genetic variants associated with neuroblastoma risk, aiming to improve diagnosis, prognosis, and treatment strategies for pediatric cancers.
Research topics
- Computational biology
- Genetics
- Biology
- Medicine
- Cancer research
- Bioinformatics
- Internal medicine
- Computer Science
- World Wide Web
- Pathology
- Immunology
- Intensive care medicine
- Endocrinology
Selected publications
The Lancet Diabetes & Endocrinology · 2023 · 102 citations
- Medicine
- Internal medicine
- Intensive care medicine
BACKGROUND: The EMPA-KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. METHODS: , or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. FINDINGS: per year (95% CI 1·16-1·59), representing a 50% (42-58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). INTERPRETATION: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. FUNDING: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council.
MITI minimum information guidelines for highly multiplexed tissue images
Nature Methods · 2022 · 85 citations
- Computer Science
- Computer Science
- Computational biology
Epigenetic state determines inflammatory sensing in neuroblastoma
Proceedings of the National Academy of Sciences · 2022 · 51 citations
- Biology
- Cancer research
- Immunology
Immunotherapy has revolutionized cancer treatment, but many cancers are not impacted by currently available immunotherapeutic strategies. Here, we investigated inflammatory signaling pathways in neuroblastoma, a classically "cold" pediatric cancer. By testing the functional response of a panel of 20 diverse neuroblastoma cell lines to three different inflammatory stimuli, we found that all cell lines have intact interferon signaling, and all but one lack functional cytosolic DNA sensing via cGAS-STING. However, double-stranded RNA (dsRNA) sensing via Toll-like receptor 3 (TLR3) was heterogeneous, as was signaling through other dsRNA sensors and TLRs more broadly. Seven cell lines showed robust response to dsRNA, six of which are in the mesenchymal epigenetic state, while all unresponsive cell lines are in the adrenergic state. Genetically switching adrenergic cell lines toward the mesenchymal state fully restored responsiveness. In responsive cells, dsRNA sensing results in the secretion of proinflammatory cytokines, enrichment of inflammatory transcriptomic signatures, and increased tumor killing by T cells in vitro. Using single-cell RNA sequencing data, we show that human neuroblastoma cells with stronger mesenchymal signatures have a higher basal inflammatory state, demonstrating intratumoral heterogeneity in inflammatory signaling that has significant implications for immunotherapeutic strategies in this aggressive childhood cancer.
Cancer Research · 2021 · 64 citations
- Biology
- Cancer research
- Bioinformatics
, the inability to obtain structural information on MYCN protein complexes, and the challenges of using traditional small molecules to inhibit protein-protein or protein-DNA interactions. However, there is now promise for directly targeting MYCN based on scientific and technological advances on all of these fronts. Here, we discuss prior challenges and the reasons for renewed optimism in directly targeting this "undruggable" transcription factor, which we hope will lead to improved outcomes for patients with pediatric cancer and create a framework for targeting driver oncoproteins regulating gene transcription.
Nature Communications · 2020 · 86 citations
- Genetics
- Biology
- Computational biology
). We uncover CNV associations with four major disease categories, including autoimmune, cardio-metabolic, oncologic, and neurological/psychiatric diseases, and identify several drug-repurposing opportunities. Our results demonstrate robust frequency definition for large-scale rare variant association studies, identify CNVs associated with major disease categories, and illustrate the pleiotropic impact of CNVs in human disease.
Cell · 2020 · 581 citations
- Biology
- Computational biology
- Bioinformatics
Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. This effort complements both ongoing efforts to map healthy organs and previous large-scale cancer genomics approaches focused on bulk sequencing at a single point in time. Generating single-cell, multiparametric, longitudinal atlases and integrating them with clinical outcomes should help identify novel predictive biomarkers and features as well as therapeutically relevant cell types, cell states, and cellular interactions across transitions. The resulting tumor atlases should have a profound impact on our understanding of cancer biology and have the potential to improve cancer detection, prevention, and therapeutic discovery for better precision-medicine treatments of cancer patients and those at risk for cancer.
Recent grants
Pediatric Preclinical Testing Consortium
NIH · $2.1M · 2015–2021
NIH · $455k · 2000
NIH · $3.0M · 2021
Discovery and Development of Optimal Immunotherapeutic Strategies for Childhood Cancers
NIH · $1.1M · 2018–2023
NIH · $2.4M · 2009
Frequent coauthors
- 864 shared
C. Patrick Reynolds
Texas Tech University Health Sciences Center
- 629 shared
Wendy B. London
- 625 shared
Susan L. Cohn
- 613 shared
Katherine K. Matthay
University of California, San Francisco
- 543 shared
Robert C. Seeger
- 529 shared
Sharon J. Diskin
Children's Hospital of Philadelphia
- 510 shared
Yaël P. Mossé
University of Pennsylvania
- 490 shared
Malcolm A. Smith
Awards & honors
- Giulio D'Angio Endowed Chair in Neuroblastoma Research
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