About

Kristina Cole, MD, PhD, is an Associate Professor of Pediatrics (Oncology) at the Children's Hospital of Philadelphia, within the Department of Pediatrics. She holds a BS in Chemistry from Dickinson College, obtained in 1992, a PhD in Pathology from the University of Maryland in 1999, and an MD in Medicine from the University of Maryland in 2001. Her research focuses on pediatric oncology, with particular emphasis on brain tumors and gliomas, as evidenced by her publications on pediatric high-grade glioma, diffuse hemispheric glioma, and recurrent pediatric central nervous system tumors. Her work involves multi-omic analyses, tumor development, and immunotherapy approaches, contributing to the understanding of the biological landscape and treatment strategies for pediatric brain cancers.

Research topics

• Biology
• Computer Science
• Bioinformatics
• Genetics
• Medicine
• Computational biology
• Pathology
• World Wide Web
• Oncology

Selected publications

• The children's brain tumor network (CBTN) - Accelerating research in pediatric central nervous system tumors through collaboration and open science

  UNC Libraries · 2025-07-26

  articleOpen access
  PublisherDOI

• Germline pathogenic variation impacts somatic alterations and patient outcomes in pediatric CNS tumors

  medRxiv · 2025-02-06

  preprintOpen access

  The contribution of rare pathogenic/likely pathogenic (P/LP) germline variants to pediatric central nervous system (CNS) tumor development remains understudied. Here, we characterized the prevalence and clinical significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumor patients from the Pediatric Brain Tumor Atlas (PBTA). We identified germline P/LP variants in 23.3% (193/830) of patients and the majority (137/193) lacked clinical reporting of genetic tumor syndromes. Among P/LP carriers, 34.6% had putative somatic second hits or loss of function tumor alterations. Finally, we linked pathogenic germline variation with novel somatic events and patient survival to highlight the impact of germline variation on tumorigenesis and patient outcomes.

  PublisherDOI

• Measles Oncolytic Virus as an Immunotherapy for Recurrent/Refractory Pediatric Medulloblastoma and Atypical Teratoid/Rhabdoid Tumor: Results from PNOC005

  Clinical Cancer Research · 2025-06-20 · 9 citations

  articleOpen access

  PURPOSE: Pediatric recurrent medulloblastoma and atypical teratoid/rhabdoid tumor (ATRT) are largely incurable and warrant novel therapies. PNOC005 is a phase I clinical trial investigating the safety and tolerability of intratumoral or intrathecal administration of oncolytic measles virus (MV-NIS) in children and young adults with recurrent medulloblastoma or ATRT. PATIENTS AND METHODS: We investigated (i) the safety of a measles virus variant, MV-NIS, in a pediatric phase I study and (ii) the mechanisms of MV-NIS and the potential benefit of combination with immune checkpoint inhibition (ICI). Pediatric patients with recurrent medulloblastoma or ATRT were treated with intratumoral injections for local recurrence or via lumbar puncture for disseminated recurrence. We evaluated local immune responses to MV-NIS with and without ICI via single-cell and bulk RNA sequencing in an intracranial, immunocompetent, syngeneic murine model. RESULTS: MV-NIS given intratumorally or via repeat intrathecal dosing was safe. MV-NIS prolonged survival in murine models but did not demonstrate an additive benefit with ICI. No changes in tumor-infiltrating immune cell composition or activation were observed in response to MV-NIS treatment; however, MV-NIS induced local expression of neutralizing antibodies, complement cascade, and phagocytosis-related genes. CONCLUSIONS: This is the first trial investigating intratumoral as well as repeated intrathecal delivery of MV-NIS in children with medulloblastoma and ATRT. We show that the therapy is safe and well tolerated, with minimal adverse effects. Immune markers and biological correlates preliminarily indicate antiviral effects in tumors.

  PublisherOA PDFDOI

• Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence

  Cancer Cell · 2025-12-11 · 11 citations

  articleOpen access
  PublisherOA PDFDOI

• Germline pathogenic variation impacts somatic alterations and patient outcomes in pediatric central nervous system tumors

  Nature Communications · 2025-11-21

  articleOpen access

  The contribution of rare pathogenic/likely pathogenic (P/LP) germline variants to pediatric central nervous system (CNS) tumor development remains understudied. Here, we characterize the prevalence and biological significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumor patients from the Pediatric Brain Tumor Atlas (PBTA). We identify germline P/LP variants in 23.3% (193/830) of patients and the majority (137/193) lack clinical reporting of genetic tumor syndromes. Among P/LP carriers, 34.6% have putative somatic second hits or loss of function tumor alterations. Finally, we link pathogenic germline variation with somatic events and patient survival to highlight the impact of germline variation on tumorigenesis and patient outcomes. The role of rare pathogenic/likely pathogenic (P/LP) germline variants in pediatric central nervous system (CNS) tumour development remains poorly understood. Here, the authors investigate the prevalence and clinical significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumour patients.

  PublisherDOI

• Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-14 · 2 citations

  preprintOpen access

  Gliomas are among the most lethal cancers, with limited treatment options. To uncover hallmarks of therapeutic escape and tumor microenvironment (TME) evolution, we applied spatial proteomics, transcriptomics, and glycomics to 670 lesions from 310 adult and pediatric patients. Single-cell analysis shows high B7H3+ tumor cell prevalence in glioblastoma (GBM) and pleomorphic xanthoastrocytoma (PXA), while most gliomas, including pediatric cases, express targetable tumor antigens in less than 50% of tumor cells, potentially explaining trial failures. Longitudinal samples of isocitrate dehydrogenase (IDH)-mutant gliomas reveal recurrence driven by tumor-immune spatial reorganization, shifting from T-cell and vasculature-associated myeloid cell-enriched niches to microglia and CD206+ macrophage-dominated tumors. Multi-omic integration identified N-glycosylation as the best classifier of grade, while the immune transcriptome best predicted GBM survival. Provided as a community resource, this study opens new avenues for glioma targeting, classification, outcome prediction, and a baseline of TME composition across all stages.

  PublisherOA PDFDOI

• Data from Measles Oncolytic Virus as an Immunotherapy for Recurrent/Refractory Pediatric Medulloblastoma and Atypical Teratoid/Rhabdoid Tumor: Results from PNOC005

  2025-08-14 · 1 citations

  articleOpen access

  <div>AbstractPurpose:<p>Pediatric recurrent medulloblastoma and atypical teratoid/rhabdoid tumor (ATRT) are largely incurable and warrant novel therapies. PNOC005 is a phase I clinical trial investigating the safety and tolerability of intratumoral or intrathecal administration of oncolytic measles virus (MV-NIS) in children and young adults with recurrent medulloblastoma or ATRT.</p>Patients and Methods:<p>We investigated (i) the safety of a measles virus variant, MV-NIS, in a pediatric phase I study and (ii) the mechanisms of MV-NIS and the potential benefit of combination with immune checkpoint inhibition (ICI). Pediatric patients with recurrent medulloblastoma or ATRT were treated with intratumoral injections for local recurrence or via lumbar puncture for disseminated recurrence. We evaluated local immune responses to MV-NIS with and without ICI via single-cell and bulk RNA sequencing in an intracranial, immunocompetent, syngeneic murine model.</p>Results:<p>MV-NIS given intratumorally or via repeat intrathecal dosing was safe. MV-NIS prolonged survival in murine models but did not demonstrate an additive benefit with ICI. No changes in tumor-infiltrating immune cell composition or activation were observed in response to MV-NIS treatment; however, MV-NIS induced local expression of neutralizing antibodies, complement cascade, and phagocytosis-related genes.</p>Conclusions:<p>This is the first trial investigating intratumoral as well as repeated intrathecal delivery of MV-NIS in children with medulloblastoma and ATRT. We show that the therapy is safe and well tolerated, with minimal adverse effects. Immune markers and biological correlates preliminarily indicate antiviral effects in tumors.</p></div>

  PublisherDOI

• A comparative analysis of IDH-mutant glioma in pediatric, young adult, and older adult patients

  Neuro-Oncology · 2024-07-31 · 13 citations

  articleOpen access

  BACKGROUND: The frequency and significance of IDH mutations in glioma across age groups are incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes. METHODS: Clinical, histologic, and sequencing data from patients with IDH-mutant, grades 2-4 gliomas, were collected from collaborating institutions between 2013 and 2019. Patients were categorized as pediatric (<19 years), young adult (YA; 19-39 years), or older adult (≥40 years). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher's exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine the association of age and other covariates with overall (OS) and progression-free survival (PFS). RESULTS: We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS. CONCLUSIONS: IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approaches varied significantly by patient age and warrant further study as addressable age-associated outcome drivers.

  PublisherOA PDFDOI

• METB-14. INTEGRATED GERMLINE AND SOMATIC PROFILING OF PEDIATRIC BRAIN TUMORS REVEALS INCIDENTAL FINDINGS AND NOVEL TUMOR BIOLOGY

  Neuro-Oncology · 2024-06-18

  articleOpen access

  Abstract BACKGROUND The contribution of rare pathogenic germline variation to central nervous system (CNS) tumor formation in pediatric patients without a family history of cancer remains unclear. METHODS We characterized the prevalence of pathogenic germline variants in 214 cancer predisposition genes (CPGs) in 837 patients profiled in the Pediatric Brain Tumor Atlas by whole genome or exome sequencing (n=820 and n=17, respectively). Rare SNVs and small INDELs were annotated as pathogenic (P) or likely pathogenic (LP) consistent with American College of Medical Genetics criteria using AutoGVP, our open-source automated pathogenicity assessment tool. We classified pathogenicity of germline structural variants (SVs) using ClassifyCNV and AnnotSV. Somatic alterations and mutational signatures from matched tumor sequencing were integrated to identify functional consequences associated with germline pathogenic variation. RESULTS We observed 206 germline P/LP SNVs/small INDELs and 18 SVs (16 deletions, 2 duplications) within 78 unique CPGs in 195 patients (23.3%). We detected syndrome-associated P/LP variants in 45/58 patients with a clinically-reported cancer predisposition syndrome and incidentally in 41 patients. Ninety-five (42%) germline P/LP variants co-occurred with at least one somatic alteration in the same gene in matched tumors: n=6 oncogenic SNVs, n=28 CNVs, n=54 loss of heterozygosity (LOH), n=26 differential gene or protein expression, and n=18 alternative splicing. NF1, TSC1, and TSC2 germline P/LP carriers exhibited significantly higher tumor LOH scores and lower gene expression in tumors relative to non-P/LP carriers. Patients with germline splice region P/LP variants exhibited significantly increased skipping of most the proximal exon in matched tumor relative to patients with non-splice region P/LP variants (W=401, p=1.1E-04). CONCLUSION We have identified rare germline P/LP variants associated with cancer predisposition syndromes and diverse functional consequences in pediatric CNS tumor patients. Efforts are underway to extend this work to include 1,801 additional probands and 1,105 parents to further characterize the prevalence and heritability of germline pathogenic variation in children diagnosed with CNS tumors.

  PublisherOA PDFDOI

• A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma

  Cell Reports Medicine · 2024-03-08 · 6 citations

  preprintOpen access

  Summary Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities to adult glioma, it is increasingly recognized as a molecularly distinct, yet highly heterogeneous disease. In this study, we longitudinally profiled a molecularly diverse cohort of 16 pHGG patients before and after standard therapy through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of the tumor microenvironment during progression following treatment. We found that the canonical neoplastic cell phenotypes of adult glioblastoma are insufficient to capture the range of tumor cell states in a pediatric cohort and observed differential tumor-myeloid interactions between malignant cell states. We identified key transcriptional regulators of pHGG cell states and did not observe the marked proneural to mesenchymal shift characteristic of adult glioblastoma. We showed that essential neuromodulators and the interferon response are upregulated post-therapy along with an increase in non-neoplastic oligodendrocytes. Through in vitro pharmacological perturbation, we demonstrated novel malignant cell-intrinsic targets. This multiomic atlas of longitudinal pHGG captures the key features of therapy response that support distinction from its adult counterpart and suggests therapeutic strategies which are targeted to pediatric gliomas.

  PublisherDOI

Recent grants

• NIH Grant K08CA136979

  NIH · $798k · 2014

• Center for Pediatric Tumor Cell Atlas - Admin Supplement

  NIH · $16.2M · 2023–2025

Frequent coauthors

• John M. Maris

  282 shared

• Sharon J. Diskin

  Children's Hospital of Philadelphia

  158 shared

• Bruce Pawel

  128 shared

• Edward F. Attiyeh

  Children's Hospital of Philadelphia

  108 shared

• David S. Walton

  100 shared

• P. B. Farmer

  University of Leicester

  100 shared

• Wen‐Chi Foo

  100 shared

• L Fajardo

  Driscoll Children's Hospital

  100 shared