A5023866306- Glioma Diagnosis and Treatment
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Single-cell and spatial transcriptomics
- Stress Responses and Cortisol
- Cancer-related cognitive impairment studies
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Protein Degradation and Inhibitors
- Cancer, Stress, Anesthesia, and Immune Response
- Bone and Joint Diseases
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- 14-3-3 protein interactions
- Ubiquitin and proteasome pathways
- Gut microbiota and health
- Virus-based gene therapy research
- Peroxisome Proliferator-Activated Receptors
- Peptidase Inhibition and Analysis
- Wnt/β-catenin signaling in development and cancer
Loyola University Chicago
2008-2025
Neurological Surgery
2015-2023
Loyola University Medical Center
2012-2023
Northwestern University
2015-2022
University of Chicago
2013-2014
Institute of Cell Biology and Neurobiology
2012
Burn Institute
2012
VA San Diego Healthcare System
2010
University of California, San Diego
2010
VA Long Beach Healthcare System
2010
Abstract Purpose: Glioblastoma is the most aggressive primary brain tumor in adults with a median survival of 15–20 months. Numerous approaches and novel therapeutics for treating glioblastoma have been investigated setting phase III clinical trials, including recent analysis immune checkpoint inhibitor, nivolumab (anti-PD-1), which failed to improve recurrent patient survival. However, rather than abandoning inhibitor treatment glioblastoma, has shown promise other types cancer, ongoing...
Purpose: Indoleamine 2,3 dioxygenase 1 (IDO1) mediates potent immunosuppression in multiple preclinical models of cancer. However, the basis for elevated IDO1 expression human cancer, including most common primary malignant brain tumor adults, glioblastoma (GBM), is poorly understood. The major objective this study to address gap our understanding how contributes biology GBM, and whether its level a determinant GBM patient outcome.Experimental Design: Patient-resected Cancer Genome Atlas,...
Background: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and associated with a median overall survival (mOS) of 16-21 months. Our previous work found negative association between advanced aging benefit after treatment immunotherapy an experimental model. Given recent phase III clinical success patients many types cancer, but not for GBM, we hypothesize that enhances immunosuppression contributes to lack efficacy improve mOS malignant glioma. Herein, compare...
Abstract Purpose: Wild-type isocitrate dehydrogenase–expressing glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median age at diagnosis of ≥65 years. It accounts for approximately 90% all GBMs has overall survival (OS) <15 months. Although immune checkpoint blockade (ICB) therapy achieved remarkable benefits in variety malignancies, similar success yet to be GBM among phase III clinical trials date. Our study aimed understand relationship between...
Glioblastoma (GBM) is an incurable primary brain tumor that has not benefited from immunotherapy to date. More than 90% of GBM expresses the tryptophan (Trp) metabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO). This observation supported historical hypothesis IDO suppresses antitumor immune response solely through a mechanism requires intratumoral Trp depletion. However, recent findings led us investigate alternative anti-GBM independent its association with metabolism.IDO-deficient cell...
Background Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments clinical trials. Results from these studies suggested that tumor microenvironment remodeling is required to achieve an effective response solid tumors. Here, we assess the extent which targeting specific mechanisms underlying immunosuppressive optimizes viroimmunotherapy. Methods We used RNA-seq analyses analyze transcriptome, validated results using Q-PCR, flow cytometry,...
Indoleamine 2,3-dioxygenase 1 (IDO1) is a potent immunosuppressive enzyme that inhibits the antitumor immune response through both tryptophan metabolism and non-enzymatic functions. To date, most IDO1-targeted approaches have focused on inhibiting metabolism. However, this class of drugs has failed to improve overall survival patients with cancer. Here, we developed characterized proteolysis targeting chimeras (PROTACs) degrade IDO1 protein. IDO1-PROTACs were tested for their effects...
Indoleamine 2,3-dioxygenase 1 (IDO1) is a potently immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and non-enzymatic functions. Pharmacological therapies targeting IDO1 enzyme activity have generally failed to improve the overall survival of patients with cancer. Developing new therapeutic agents are capable neutralizing enzyme-and non-enzyme-derived effects therefore high interest. We previously described development novel Proteolysis Targeting...
Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and nonenzymatic functions. Drugs targeting IDO1 enzyme activity have failed to improve the overall survival of patients with cancer. Developing new therapeutics neutralize enzyme- nonenzyme-derived effects therefore high interest. We previously described a novel proteolysis chimera (PROTAC), NU223612, degrades in cultured human glioblastoma (GBM) cells, as...
Background Alcohol abuse is a risk factor for bone damage and fracture‐related complications. Through precise β‐catenin signaling, canonical W nt signaling plays key role in fracture repair by promoting the differentiation of new cartilage cells. In this study, we examined effects alcohol on pathway injured using murine model alcohol‐induced impaired healing. Methods Male C 57 B l/6 or T cell ( TCF )‐transgenic mice were administered 3 daily intraperitoneal doses saline. One hour following...
Clinical studies have shown alcohol to be a risk factor for traumatic orthopaedic injuries and nonunion. Data from animal suggest that exposure inhibits fracture healing. This report presents novel rodent model of impaired healing caused by repeated exposure. Using this model, we examined the regenerative effects an intravenously administered population isolated expanded mesenchymal stem cells (MSCs) on healing.Bone marrow-derived MSC were transgenic green fluorescent protein C57BL/6 mice,...
Abstract Purpose: Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset 68 to 70 years old. Although advanced often associated poorer GBM patient survival, predominant source(s) maladaptive aging effects remains be established. Here, we studied intratumoral and extratumoral relationships between adult patients mice tumors across lifespan. Experimental Design: Electronic health records at Northwestern Medicine NCI SEER databases...
Glioblastoma (GBM) is the most common and aggressive form of malignant glioma in adults with a median overall survival (OS) time 16-18 months age diagnosis at 64 years old. Recent work has suggested that depression psychosocial distress are associated worse outcomes patients GBM. We therefore hypothesized targeted neutralization selective serotonin reuptake inhibitor (SSRI) antidepressant treatment would be longer OS among To address this hypothesis, we retrospectively studied association...