Project Grant F31CA306101
- This Project Grant award from the National Cancer Institute (CFDA 93.398 - Cancer Research Manpower) provides $162,486 to Case Western Reserve University to study translation regulation in glioblastoma stem-like cells (GSCs) and their adaptation to hypoxic tumor environments. The research aims to gain a better understanding of GSC biology and the post-transcriptional regulatory mechanisms that enable them to thrive in both low and normal oxygen conditions, promoting glioblastoma tumor growth....
- This Project Grant award from the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research) provides $451,996 to the University of Texas at Arlington (UTA) to develop high-throughput screening platforms for identifying and validating drugs that can target migrating and treatment-resistant glioblastoma (GBM) cancer cells. The overarching goal is to transform GBM, which is currently a fatal disease, into a more localized condition that can be effectively treated through surgery and/or...
- This federal Project Grant award, valued at $641,936 and funded by the National Cancer Institute (CFDA 93.395 - Cancer Treatment Research), aims to develop novel strategies to program tumor-associated neutrophils as antitumor effector cells for the treatment of glioblastoma (GBM), the most aggressive type of brain cancer. The project will leverage synthetic biology, machine learning, and next-generation sequencing to interrogate tumor-associated neutrophils and develop methods to reprogram...
- This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program will support research on a novel signaling axis involving the protein connexin 43 (CX43) and its role in regulating cancer stem cells in glioblastoma, the most common and deadly form of brain cancer. The $161,000 award to the Cleveland Clinic Lerner College of Medicine of Case Western Reserve...
- This federal Project Grant award of $131,360 from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, is funding research at the University of New Haven to characterize the long non-coding RNA GIHCG and assess its potential as a therapeutic target for glioblastoma, the most aggressive form of brain cancer. The 4-year project aims to use CRISPR/Cas9 gene editing to...
- This $997,410 Project Grant award from the National Cancer Institute under the Cancer Detection and Diagnosis Research program (CFDA 93.394) aims to develop non-invasive MRI-based techniques to detect and differentiate between the invasive neuronal (NEU) and glycolytic/plurimetabolic (GPM) subtypes of high-grade glioma brain tumors. The project leverages recent discoveries about these tumor subtypes' distinct microstructural, metabolic, and synapse profiles to enable more comprehensive tumor...
- This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) provides $848,286 to the University of South Florida to conduct research on the role of N6-methyladenosine (m6A) RNA modifications in Alzheimer's disease (AD). The key objectives are to: 1) Create a high-resolution map of m6A sites in the brains of older adults, 2) Identify specific m6A alterations associated with AD and its clinical/pathological features, and 3) Elucidate how m6A dysregulation may...
- This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, aims to develop novel small molecule inhibitors targeting the MBD2 protein for epigenetic therapy of medulloblastoma (MB), a common and aggressive pediatric brain cancer. The $564,045 award supports medicinal chemistry optimization of a lead compound, KCC07, which has shown promise in...
- This Project Grant award of $687,279 from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) supports research to uncover the effects of standard-of-care therapy on immune and neoplastic cell population dynamics in pre-clinical mouse models of glioblastoma (GBM) and analysis of human GBM samples. The goal is to identify tumor microenvironment areas of therapeutic...
- This federal Project Grant award of $433,125.00, provided by the National Institute of Neurological Disorders and Stroke (NINDS) through the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, supports research to investigate the role of the RNA binding protein SERBP1 in regulating epigenetic processes and gene expression changes that contribute to glioblastoma development and cell fate decisions. The key objectives are to establish connections...
INVESTIGATING THE ROLE OF N6-METHYLADENOSINE IN THE DEVELOPMENT OF DRUG RESISTANCE IN GLIOBLASTOMA - PROJECT SUMMARY RNA CHEMICAL MODIFICATIONS ARE CRITICAL REGULATORS OF GENE EXPRESSION THROUGH REGULATION OF RNA STABILITY, SPLICING, TRANSLATION, STRUCTURE, AND LOCALIZATION. BECAUSE OF THEIR IMPORTANT ROLES IN SEVERAL BIOLOGICAL PATHWAYS, RNA MODIFICATIONS ARE FREQUENTLY IMPLICATED IN DISEASE. N6-METHYLADENOSINE (M6A), THE MOST PREVALENT INTERNAL RNA MODIFICATION IN EUKARYOTIC MESSENGER RNA (MRNA), HAS BEEN EXTENSIVELY STUDIED AND IMPLICATED IN A WIDE-ARRAY OF HUMAN DISEASES, MOST NOTABLY CANCER. DUE TO THE ESTABLISHED ROLE OF M6A IN CANCER, M6A AND ITS ASSOCIATED MACHINERY HAVE BEEN PROPOSED AS POTENTIAL DIAGNOSTIC AND PREDICTIVE BIOMARKERS AND THERAPEUTIC TARGETS. ALTHOUGH THE ROLE OF M6A IN SEVERAL CANCER IS RELATIVELY WELL-ESTABLISHED, ITS REGULATORY ROLE IN GLIOBLASTOMA (GBM) PATHOGENESIS REMAINS LARGELY UNCLEAR. GBM, A GRADE IV GLIOMA TUMOR, IS THE MOST COMMON PRIMARY MALIGNANT BRAIN TUMOR. GBM IS A DEVASTATING DISEASE ASSOCIATED WITH POOR PATIENT PROGNOSIS, LIMITED THERAPEUTIC OPTIONS, AND FREQUENT RECURRENCE WITH ACQUIRED THERAPY RESISTANCE. BECAUSE M6A HAS BEEN EXTENSIVELY DEMONSTRATED TO PLAY AN IMPORTANT REGULATORY ROLE IN CANCER, THE GOAL OF MY PROPOSAL IS TO CHARACTERIZE MOLECULAR MECHANISMS BY WHICH M6A REGULATES GBM PATHOGENESIS, AND UNCOVER HOW MANIPULATION OF M6A REGULATION MAY IMPROVE GBM TREATMENT. THE FIRST PORTION OF MY RESEARCH WILL EXAMINE THE MECHANISM BY WHICH M6A POST-TRANSCRIPTIONALLY REGULATES MGMT, A CRITICAL BIOMARKER AND PREDICTOR OF CHEMOTHERAPY RESPONSE IN GBM. TO ACCOMPLISH THIS, I WILL MAP M6A SITES ON MGMT MRNA, DETERMINE HOW DISRUPTING M6A INSTALLATION ON MGMT AFFECTS MGMT EXPRESSION AND STABILITY, AND IDENTIFY READER PROTEINS WHICH FACILITATE THIS EFFECT. I WILL THEN DETERMINE THE CONSEQUENCES OF THIS REGULATORY MECHANISM ON CHEMORESISTANCE OF GLIOMA CELLS. IN THE SECOND PORTION OF MY RESEARCH, BUILDING UPON PRELIMINARY RNA SEQUENCING DATA, I WILL INVESTIGATE MECHANISMS TRANSCRIPTOME-WIDE AS TO HOW M6A REGULATES THE TRANSCRIPTOME OF GLIOMA CELLS IN RESPONSE TO CHRONIC TREATMENT WITH AN ALKYLATING AGENT. TO ACCOMPLISH THIS, IN CHEMORESISTANT GLIOMA CELLS, I WILL (1) MAP M6A SITES, (2) TEMPORALLY SEQUENCE RNAS TO MEASURE THE EFFECT OF M6A PERTURBATION ON RNA STABILITY, AND (3) SEQUENCE THE INTERACTOME OF CANONICAL DOWNSTREAM REGULATORS M6A-MODIFIED TRANSCRIPTS. TOGETHER, THESE COMPLEMENTARY STUDIES WILL INCREASE OUR UNDERSTANDING OF MECHANISMS BY WHICH M6A REGULATES GBM PATHOGENESIS AND REVEAL VULNERABILITIES THAT CAN BE TARGETED WITH M6A-MEDIATED THERAPEUTICS.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $49.5k | 7/15/25 | ||
| Not listed | $49.5k | 7/15/25 | ||
| Not listed | $0 | 7/15/25 |