A5074788911- Glioma Diagnosis and Treatment
- Tryptophan and brain disorders
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Immunotherapy and Biomarkers
- Ferroptosis and cancer prognosis
- Protein Degradation and Inhibitors
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Gut microbiota and health
- Nanoplatforms for cancer theranostics
- 14-3-3 protein interactions
- Cancer-related cognitive impairment studies
- Cancer, Hypoxia, and Metabolism
- Stress Responses and Cortisol
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- RNA Interference and Gene Delivery
- bioluminescence and chemiluminescence research
- Immune Cell Function and Interaction
- Bipolar Disorder and Treatment
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Adolescent Sexual and Reproductive Health
Northwestern University
2019-2023
Loyola University Chicago
2023
Neurological Surgery
2019-2022
Ionis Pharmaceuticals (United States)
2019
University of Chicago
2017
University of North Texas
2016
University of North Texas Health Science Center
2016
University of Arkansas for Medical Sciences
1999
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...
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...
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...
Group 1 innate lymphoid cells include natural killer (NK) and ILC1s, which mediate the response to intracellular pathogens. Thymic NK (tNK) were described with hybrid features of immature ILC1 but whether these are related or has not been fully investigated. We report that murine tNK expressed NK-cell associated transcription factor EOMES developed independent essential TBET, confirming their placement within lineage. Moreover, resemble rather than in requirements for E protein inhibitor...
The protein synthesis inhibitor anisomycin activates stress-related mitogen-activated kinases (MAPKs), namely, c-jun NH2-terminal kinase (p46/54JNK) and p38MAPK in mammalian cells. In this paper, we show that although exposure to resulted rapid strong activation of p46/54JNK p38MAPK, with a delayed low level dual-phosphorylation mitogen/extracellular (p42/44MAPK), density lipoprotein (LDL) receptor induction depends solely on the mild p42/44MAPK signaling cascade HepG2 Unlike hepatocyte...
Abstract To understand the role of indoleamine 2,3 dioxygenase 1 (IDO1) in age-dependent immunotherapeutic effect, we compared 20-26 month-old C57BL/6 background mice that were IDO1-T2A-GFP [(WT); n=16], IDO1 enzyme null [H350A; (n=16)], IDO1KO (n=4), Ido1fl/fl(n=14), Lysm-Cre+→Ido1fl/fl (n=20), CD11c-Cre+→Ido1fl/fl (n=23), Tie2-Cre+→Ido1fl/fl (n=14) treated with RT + PD-1 mAb. Mice intracranially engrafted (ic.) GL261 cells followed by mAb beginning at 14-days post-ic. WT and (H350A) had a...
<div>AbstractPurpose:<p>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...
<p>Supplemental Figure 2. Histological evaluation of tumor progression and confirmation IDO-mGFP expression in brain tumors.</p>
<p>Supplemental Figure 1. Overall survival of syngeneic mice with intracranial IDO-/-tGBM tumors and depleted for CD4+ T, CD8+ NK1.1+ immune cells.</p>
Abstract Objective Indoleamine 2, 3 dioxygenase 1 (IDO1) is a rate limiting enzyme that converts tryptophan (Trp) into kynurenine (Kyn). IDO1 knockdown in murine glioblastoma (GBM) cells suppresses intratumoral regulatory T cell (Treg) recruitment and increases survival, but unexpectedly, has no effect on Trp levels. Moreover, while GBM overexpression Treg levels, treatment with pharmacological inhibitor fails to reverse this effect. These novel data led us question whether recruits Tregs...
Abstract INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO; IDO1) is a rate-limiting enzyme that metabolizes the essential amino acid tryptophan into kynurenine. Recent work by our group has revealed IDO promotes tumor development and suppresses immune cell functions independent of its activity. Moreover, pharmacologic inhibitors currently serve as only class drugs available for targeting immunosuppressive activity, fail to improve survival patients with GBM. Here, we developed IDO-Proteolysis...
Abstract De novo glioblastoma (GBM) represents ≥ 90% of all GBM diagnoses and has a median age onset at 65 years old. Because its preponderance during advanced age, we investigated the mortality rate older adult C57BL/6 (WT) mice with CT-2A glioma. Strikingly, discovered significant decrease overall survival among animal subjects depleted for both CD4+ CD8+ T cells as compared to group treated IgG control antibodies. This negative effect lymphopenia only applied adults. We next questioned...
Abstract INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO) is an immunosuppressive enzyme that catabolizes the essential amino acid, tryptophan (Trp), into metabolite, kynurenine. IDO expressed in &gt;90% of patient resected GBM. suppresses anti-brain tumor immune response, in-part, through non-metabolic activities. To determine how non-metabolically anti-GBM IDO-protein degrader (IDO-proteolysis targeting chimera; IDO-PROTAC) effects were studied multiple human models METHODS The...
Abstract OBJECTIVE Indoleamine 2,3-dioxygenase 1 (IDO; IDO1) is an immune checkpoint that’s characterized as a potent immunosuppressive mediator through its ability to metabolize tryptophan and wild-type IDH patient-resected glioblastoma (GBM) expresses IDO in ≥ 95% of cases. Recent findings from our group led us investigate the alternative hypothesis that possesses effects are independent associated metabolic activity. METHODS Murine GBM cell lines overexpress either or enzyme-null were...
Advancement in healthcare-related technologies has resulted a groundswell of information contained patient health records. Electronic data abstraction systems have allowed medical professionals to analyze and apply vast bodies comprehensively. In the field clinical trial management, electronic capture (EDC) become vital this process. Over time, EDC yields benefits cost, duration, capacity utilize remote monitoring. However, implementation can prove costly, often causes temporary disruptions...
<p>Supplemental Figure 1. Inclusion and exclusion criteria for the analysis of human subjects diagnosed with glioblastoma (GBM).</p>