A5017932845- Glioma Diagnosis and Treatment
- Cancer Cells and Metastasis
- Radiomics and Machine Learning in Medical Imaging
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- interferon and immune responses
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Hypoxia, and Metabolism
- TGF-β signaling in diseases
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Gene expression and cancer classification
- Metabolomics and Mass Spectrometry Studies
- Immune Cell Function and Interaction
- Cancer-related molecular mechanisms research
- Cancer Research and Treatments
- Acute Myeloid Leukemia Research
- Hepatitis Viruses Studies and Epidemiology
- Artificial Intelligence in Healthcare
- Salmonella and Campylobacter epidemiology
- Neurogenesis and neuroplasticity mechanisms
- Retinoids in leukemia and cellular processes
- Brain Metastases and Treatment
University of Michigan
2020-2024
The University of Texas MD Anderson Cancer Center
2017-2021
Ann Arbor Center for Independent Living
2021
Indian Institute of Science Bangalore
2017
We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique features, clinically significant subtypes, potential therapeutic targets. found 61 somatic copy-number alterations (SCNAs) 46 significantly mutated genes (SMGs). Eleven SCNAs 11 SMGs had not been identified in previous TCGA studies the individual tumor types. functionally estrogen receptor-regulated long non-coding RNAs (lncRNAs)...
We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types The Cancer Genome Atlas (TCGA). Focusing on genes encode mediators and regulators TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) 39% samples, with highest frequencies gastrointestinal cancers. identified mutation hotspots ligands (BMP5), receptors (TGFBR2,...
Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children USA. Sixteen percent hemispheric pediatric and young adult HGGs encode Gly34Arg/Val substitutions histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy therapeutic resistance pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) human pHGG cells encoding H3.3-G34R, we demonstrate that this mutation led to downregulation DNA repair pathways....
Lipid-rich myelin forms electrically insulating, axon-wrapping multilayers that are essential for neural function, and mature is traditionally considered metabolically inert. Surprisingly, we discovered lipids undergo rapid turnover, quaking (Qki) a major regulator of lipid homeostasis. Oligodendrocyte-specific Qki depletion, without affecting oligodendrocyte survival, resulted in demyelination, within 1 week, gradually neurological deficits adult mice. Myelin lipids, especially the...
Intraperitoneal dissemination of ovarian cancers is preceded by the development chemoresistant tumors with malignant ascites. Despite high levels chemoresistance and relapse observed in cancers, there are no vitro models to understand situ. Method: We describe a highly integrated approach establish an model stemness cancer, using 3D hanging drop spheroid platform. The was established serially passaging non-adherent spheroids. At each passage, effectiveness evaluated via measures...
Lysine-specific demethylase 1 (LSD1) is a histone that promotes stemness and cell survival in cancers such as prostate cancer. Most malignancies are adenocarcinomas with luminal differentiation. However, some tumors undergo cellular reprogramming to more lethal subset termed neuroendocrine cancer (NEPC) neuronal The frequency of NEPC increasing since the widespread use potent androgen receptor signaling inhibitors. Currently, there no effective treatments for NEPC. We previously determined...
It remains unknown whether and how intestinal stem cells (ISCs) adapt to inflammatory exposure the adaptation leaves scars that will affect their subsequent regeneration. We investigated consequences of inflammation on Lgr5
INTRODUCTION: Glioblastoma(GBM) is a lethal intracranial neoplasm that inevitably recurs despite treatment with DNA damaging therapies, radiation(RT) and temozolomide(TMZ). Recurrence likely driven by inherently resistant glioma stem-like cells(GSCs), which have baseline upregulation of damage response(DDR) pathways due to elevated replication stress(RS). Elevated DDR confers resistance RT/TMZ however factors mediating RS therefore upregulated in GSC are poorly defined. METHODS: THY1 was...
Histone H3.3G34R/V mutant gliomas demonstrate LIF/STAT pathway activation that can be disrupted for therapeutic benefit.
Glioblastoma(GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with goal of identifying novel therapeutic opportunities. We developed longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens(pre- and post-recurrence) following temozolomide(TMZ) radiation(IR). These specimens were evaluated for treatment response identify gene expression driving resistance. Findings...
Focal adhesion kinase (FAK) promotes cancer cell growth and metastasis. We previously reported that FAK inhibition by the selective inhibitor VS-4718 exerted antileukemia activities in acute myeloid leukemia (AML). The mechanisms involved, whether potentiates efficacy of other therapeutic agents, have not been investigated. Resistance to apoptosis inducted BCL-2 ABT-199 (venetoclax) AML is mediated preexisting ABT-199-induced overexpression MCL-1 BCL-XL. observed or silencing with siRNA...
<h3>BACKGROUND AND PURPOSE:</h3> The T2-FLAIR mismatch sign is a validated imaging of <i>isocitrate dehydrogenase</i>–mutant 1p/19q noncodeleted gliomas. It identified by radiologists through visual inspection preoperative MR scans and has been shown to identify gliomas with high positive predictive value. We have developed an approach quantify the signature use it predict molecular status lower-grade <h3>MATERIALS METHODS:</h3> used multiparametric segmentation labels 108 glioma tumors from...
CD4+ T-cell response is vital for successful clearance of Salmonella Typhimurium infection. Efficient antigen presentation crucial effective response. Previous study has reported that abrogates capacity dendritic cells in order to escape host adaptive immune In this study, we have elucidated the mechanism Salmonella-mediated downregulation total cellular Major Histocompatibility Complex (MHC) II pool cells. Infected show upregulation E3 ubiquitin ligase, MARCH1 expression and K63-linked...
Chordomas are aggressive bone tumors that often recur despite maximal resection and adjuvant radiation. To date there no Food Drug Administration (FDA)-approved chemotherapies. Computational drug repositioning is an expanding approach to identify pharmacotherapies for clinical trials.
Intestinal stem cells (ISC) encounter inflammatory insults in immune mediated gastro-intestinal (GI) diseases. It remains unknown whether, and how, they adapt, if the adaptation leaves scars on ISCs that affects their subsequent regeneration capacity. We investigated consequences of inflammation Lgr5+ISCs well-defined clinically relevant models acute graft-versus-host disease (GI GVHD). Utilizing single cell transcriptomics, organoid, metabolic, epigenomic vivo we found undergo metabolic...
Background and Purpose: Lower grade gliomas (LGGs), lesions of WHO grades II III, comprise 10-15% primary brain tumors.In this first-of-a-kind study, we aim to carry out a radioproteomic characterization LGGs using proteomics data from the TCGA imaging TCIA cohorts, obtain an association between tumor MRI characteristics protein measurements. The availability linked molecular permits assessment relationships genomic/proteomic measurements with phenotypic features. Materials Methods:...
LncRNAs are differentially expressed by allogeneic antigen-stimulated T cells, and Linc00402 regulates cells.
Abstract Glioblastoma (GBM) is a lethal disease characterized by inevitable recurrence. Recently, single cell sequencing studies of primary GBM have defined various tumor states, specifically the neural progenitor-like (NPC-like), oligodendrocyte progenitor (OPC-like), astrocyte-like(AC-like), and mesenchymal(MES-like) states. Yet, role these states play in treatment resistance recurrence not well defined. Furthermore, spatial microenvironmental (TME) context cells clearly plays response....
Abstract Glioblastoma (GBM) is a uniformly lethal primary intracranial neoplasm that inevitably recurs despite treatment by DNA damaging agents radiation (RT) and temozolomide (TMZ). Recurrence may be driven inherently resistant glioma stem-like cells (GSCs). GSCs have been shown to constitutive upregulation of damage response (DDR) pathways, resulting from elevated replication stress. This baseline DDR has consequently confer inherent resistance agents, TMZ/RT. However, factors mediating...
Abstract Rapid repair of DNA damage mediates genotoxic therapy resistance and poor prognosis in glioblastoma (GBM). The GBM tumor microenvironment (TME) is heterogenous, we hypothesized that non-malignant cells support the cells. Consistent with this hypothesis, found tumors grown intracranially mice had rapid were resistant to radiation compared identical genotype extracranially mouse flanks. Further interrogation irradiated intracranial using gamma-H2AX immunofluorescence revealed spatial...
Background: Imaging features derived from MRI scans can be used for not only breast cancer detection and measuring disease extent, but also determine gene expression patient outcomes.The relationships between imaging features, gene/ protein expression, response to therapy hold potential guide personalized medicine.We aim characterize the relationship radiologist-annotated tumor phenotypic (based on MRI) underlying biological processes proteomic profiling) in tumor.Methods: Multiple-response...