Drew Pratt
A5080146061- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- Neuroblastoma Research and Treatments
- Radiomics and Machine Learning in Medical Imaging
- Cancer Immunotherapy and Biomarkers
- Chromatin Remodeling and Cancer
- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Neurofibromatosis and Schwannoma Cases
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Biochemical and Molecular Research
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer Mechanisms and Therapy
- Histone Deacetylase Inhibitors Research
- Mitochondrial Function and Pathology
- MicroRNA in disease regulation
- Peptidase Inhibition and Analysis
- Meningioma and schwannoma management
- Cancer-related molecular mechanisms research
- Single-cell and spatial transcriptomics
- Cytomegalovirus and herpesvirus research
National Cancer Institute
2015-2025
Center for Cancer Research
2016-2025
National Institutes of Health
2015-2024
University of Michigan
2018-2023
Michigan United
2023
Anna Needs Neuroblastoma Answers
2023
University of Chicago
2023
Regional Health
2022
Michigan Medicine
2018-2021
Ann Arbor Center for Independent Living
2021
Abstract Intratumoral genomic heterogeneity in glioblastoma (GBM) is a barrier to overcoming therapy resistance. Treatments that are effective independent of genotype urgently needed. By correlating intracellular metabolite levels with radiation resistance across dozens genomically-distinct models GBM, we find purine metabolites, especially guanylates, strongly correlate Inhibiting GTP synthesis radiosensitizes GBM cells and patient-derived neurospheres by impairing DNA repair. Likewise,...
Abstract Patients with H3K27M-mutant diffuse midline glioma (DMG) have no proven effective therapies. ONC201 has recently demonstrated efficacy in these patients, but the mechanism behind this finding remains unknown. We assessed clinical outcomes, tumor sequencing, and tissue/cerebrospinal fluid (CSF) correlate samples from patients treated two completed multisite studies. following initial radiation prior to recurrence a median overall survival of 21.7 months, whereas those after had 9.3...
Abstract Background Accurate CNS tumor diagnosis can be challenging, and methylation profiling serve as an adjunct to classify diagnostically difficult cases. Methods An integrated diagnostic approach was employed for a consecutive series of 1258 surgical neuropathology samples obtained primarily in consultation practice over 2-year period. DNA classification using the DKFZ/Heidelberg classifier performed, well unsupervised analyses data. Ancillary testing, where relevant, performed. Results...
ATRX, a chromatin remodeler protein, is recurrently mutated in H3F3A-mutant pediatric glioblastoma (GBM) and isocitrate dehydrogenase (IDH)-mutant grade 2/3 adult glioma. Previous work has shown that ATRX-deficient GBM cells show enhanced sensitivity to irradiation, but the etiology remains unclear. We find ATRX binds regulatory elements of cell-cycle phase transition genes cells, there marked reduction Checkpoint Kinase 1 (CHEK1) expression with loss, leading early release G2/M entry after...
Childhood posterior fossa group A ependymomas demonstrate integrated metabolic and epigenetic pathways that can be disrupted by metformin.
Abstract Gliomas arising in the setting of neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade or high-grade, and follow an indolent aggressive clinical course. Comprehensive profiling genetic alterations beyond NF1 inactivation epigenetic classification these tumors remain limited. Through next-generation sequencing, copy number analysis, DNA methylation gliomas 47 patients, we identified 2 molecular subgroups...
Abstract Globally decreased histone 3, lysine 27 tri-methylation (H3K27me3) is a hallmark of H3K27-altered diffuse midline gliomas (DMGs) and group-A posterior fossa ependymomas (PFAs). DMGs are largely characterized by lysine-to-methionine mutations in 3 at position (H3K27M). Most PFAs overexpress EZH inhibitory protein (EZHIP), which possesses region similarity to the mutant H3K27M. Both H3K27M EZHIP inhibit function polycomb repressive complex 2 (PRC2) responsible for H3K27me3 deposition....
Abstract Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves structures, and displays loss p.K28me3 (K27me3) expression by immunohistochemistry characteristic genetic/epigenetic profile. Rare examples a glioma with p.K28M (K27M) mutation without involvement the so-called “diffuse hemispheric mutation” (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases radiologically...
Abstract Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use methylation profiling next-generation sequencing has led to identification molecularly distinct subtypes. One proposed tumor type, CNS with BRD4::LEUTX fusion, been described. As only few fusions have described, we herein characterize cohort 9 such cases (4 new, 5 previously published) further describe their clinicopathologic molecular features. We...
Abstract Papillary tumor of the pineal region (PTPR) is an uncommon with distinctive histopathologic and molecular characteristics. Experience limited respect to its heterogeneity clinical Here, we describe 39 new cases combine these 37 previously published for a cohort 76 PTPR’s, all confirmed by methylation profiling. As reported, two main groups were identified (PTPR-A PTPR-B). In our analysis extended subtyping into three subtypes: PTPR-A, PTPR-B1 PTPR-B2 supported DNA profile genomic...
The zebrafish (Danio rerio) has been at the forefront of neurobiological research and is steadily gaining favor as a model for behavioral applications. ease handling, high yield progeny, efficient mode drug delivery make this species particularly useful behavior. Here, we append to growing body literature on behavior by introducing novel battery tests aimed identifying induced alterations in social motoric behaviors. In series experiments, were exposed MK-801 (0, 2 μM, 20 μM), SFK 38393 10...
Histone H3.3G34R/V mutant gliomas demonstrate LIF/STAT pathway activation that can be disrupted for therapeutic benefit.
<p>Volcano plot of differentially expressed genes in DIPG007 cells treated with ONC201 versus vehicle.</p>
<p>Individual cases from historical control datasets.</p>
<p>Expression values, Spearman’s correlation coefficient, and GSEA of genes associated with positive or negative radiographic response to ONC201 treatment.</p>