A5026066701- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- Neuroblastoma Research and Treatments
- Mitochondrial Function and Pathology
- Chromatin Remodeling and Cancer
- Histone Deacetylase Inhibitors Research
- Estrogen and related hormone effects
- Hormonal Regulation and Hypertension
- Protein Degradation and Inhibitors
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related molecular mechanisms research
- Cancer Mechanisms and Therapy
- Prostate Cancer Treatment and Research
- RNA modifications and cancer
- Neuroscience and Neuropharmacology Research
- Adipose Tissue and Metabolism
- 14-3-3 protein interactions
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Cancer Research and Treatments
- Alzheimer's disease research and treatments
- Radiomics and Machine Learning in Medical Imaging
- Cancer Genomics and Diagnostics
University of Michigan
2016-2025
Michigan Medicine
2016-2023
Michigan Center for Translational Pathology
2021-2023
Ann Arbor Center for Independent Living
2021
Regional West Medical Center
2019
Memorial Sloan Kettering Cancer Center
2012-2015
Institut Claudius Regaud
2015
University of Pennsylvania
2011-2015
Kettering University
2015
Children's Hospital of Los Angeles
2011-2014
The de novo synthesis of the nonessential amino acid serine is often upregulated in cancer. In this study, we demonstrate that catabolic enzyme, mitochondrial hydroxymethyltransferase (SHMT2), induced when MYC-transformed cells are subjected to hypoxia. mitochondria, SHMT2 can initiate degradation CO2 and NH4+, resulting net production NADPH from NADP+. Knockdown MYC-dependent reduced cellular NADPH:NADP+ ratio, increased reactive oxygen species, triggered hypoxia-induced cell death. vivo,...
An oncohistone deranges inhibitory chromatin Missense mutations (that change one amino acid for another) in histone H3 can produce a so-called and are found number of pediatric cancers. For example, the lysine-36–to-methionine (K36M) mutation is seen almost all chondroblastomas. Lu et al. show that K36M mutant histones oncogenic, they inhibit normal methylation this same residue wild-type histones. The also interfere with development bone-related cells deposition marks. Science , issue p. 844
Quantitative SRS microscopy can detect human brain tumor infiltration with high sensitivity and specificity, even in tissues appearing grossly normal.
Glutamine-based PET imaging takes advantage of gliomas’ glutamine addiction and can be used to assess metabolic nutrient uptake in gliomas.
Mutant IDH1 coexpressed with inactivating TP53 and ATRX mutations in glioma enhances DNA repair, causing resistance to genotoxic therapies.
Abstract H3F3A mutations are seen in ∼30% of pediatric glioblastoma ( GBMs ) and involve either the lysine residue at position 27 K27M or glycine 34 G34R/V ). Sixteen genes encode histone H 3, each variant differing only a few amino acids. Therefore, how single 3 gene contribute to carcinogenesis is unknown. predicted alter methylation H3K27 . H3K27me3 repressive mark critical stem cell maintenance mediated by EZH2 , member polycomb‐group PcG family. We evaluated expression using...
A subset of childhood posterior fossa ependymomas with poor prognosis is epigenetically similar to H3K27M gliomas.
Abstract Posterior fossa type A (PFA) ependymomas exhibit very low H3K27 methylation and express high levels of EZHIP (Enhancer Zeste Homologs Inhibitory Protein, also termed CXORF67 ). Here we find that a conserved sequence in is necessary sufficient to inhibit PRC2 catalytic activity vitro vivo. directly contacts the active site EZH2 subunit mechanism similar H3 K27M oncohistone. Furthermore, expression or cells promotes chromatin profiles: loss broad H3K27me3 domains, but retention at CpG...
Tumor suppressor SMARCA4 (BRG1), a key SWI/SNF chromatin remodeling gene, is frequently inactivated in cancers and not directly druggable. We recently uncovered that loss an ovarian cancer subtype causes cyclin D1 deficiency leading to susceptibility CDK4/6 inhibition. Here, we show this vulnerability conserved non-small cell lung (NSCLC), where also results reduced expression selective sensitivity inhibitors. In addition, SMARCA2, another subunit lost subset of NSCLCs, regulates drug...
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 Diffuse Midline Glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, patients rarely surviving 2 years from diagnosis. Methods We conducted multi-site Phase 1 trial of imipridone ONC201 for children H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D (n = 24) underwent serial lumbar puncture cell-free tumor DNA (cf-tDNA) analysis and all arms at University Michigan plasma collection. performed digital droplet polymerase chain reaction...
<h3>Background</h3> Alzheimer disease (AD) is defined neuropathologically by the presence of neurofibrillary tangles and plaques associated with tau β-amyloid protein deposition. The colocalization microglia has been widely reported in pathological examination AD suggests that neuroinflammation may play a role pathogenesis and/or progression. Because postmortem histopathological analyses are limited to single end-stage assessment, time course nature this relationship not well understood....
More than 50% of patients with chondrosarcomas exhibit gain-of-function mutations in either isocitrate dehydrogenase 1 (IDH1) or IDH2. In this study, we performed genome-wide CpG methylation sequencing chondrosarcoma biopsies and found that IDH were associated DNA hypermethylation at islands but not other genomic regions. Regions island enriched for genes implicated stem cell maintenance/differentiation lineage specification. murine 10T1/2 mesenchymal progenitor cells, expression mutant IDH2...
Pediatric glioblastomas (GBM) are highly aggressive and lethal tumors. Recent sequencing studies have shown that ~30 % of pediatric GBM ~80 diffuse intrinsic pontine gliomas show K27M mutations in the H3F3A gene, a variant encoding histone H3.3. lead to global reduction H3K27me3. Our goal was develop biomarkers for histopathologic detection these Therefore, we evaluated utility measuring H3K27me3 as prognostic biomarker tested an antibody directed specifically against H3.3 mutation 290...