A5012668473- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Tryptophan and brain disorders
- Immune cells in cancer
- Cancer, Lipids, and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Diet and metabolism studies
- Adenosine and Purinergic Signaling
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Immunodeficiency and Autoimmune Disorders
- Cancer Research and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Genomics, phytochemicals, and oxidative stress
- Glutathione Transferases and Polymorphisms
- Cytomegalovirus and herpesvirus research
- Cancer, Stress, Anesthesia, and Immune Response
- Immune Response and Inflammation
- Cell death mechanisms and regulation
- Bladder and Urothelial Cancer Treatments
- Protein Degradation and Inhibitors
Beaumont Health
2017-2023
MUSC Hollings Cancer Center
2014-2019
Medical University of South Carolina
2011-2019
Oakland University
2017
Beaumont Hospital, Royal Oak
2017
College of Charleston
2015
Sanjay Gandhi Post Graduate Institute of Medical Sciences
2008-2012
Despite advances in molecularly characterizing glioblastoma (GBM), metabolic alterations driving its aggressive phenotype are only beginning to be recognized. Integrative cross-platform analysis coupling global metabolomic and gene expression profiling on patient-derived glioma identified fatty acid β-oxidation (FAO) as a node GBM. We determined that the biologic consequence of enhanced FAO is directly dependent upon tumor microenvironment. serves cue drive proliferation β-HB/GPR109A...
Abstract There has been considerable scientific effort dedicated to understanding the biologic consequence and therapeutic implications of aberrant tryptophan metabolism in brain tumors neurodegenerative diseases. A majority this work focused on upstream tryptophan; however, resulted limited clinical application. Using global metabolomic profiling patient-derived tumors, we identify downstream accumulation quinolinate (QA) as a metabolic node glioblastoma demonstrate its critical role...
Abstract Purpose: Immune checkpoint inhibitors designed to revert tumor-induced immunosuppression have emerged as potent anticancer therapies. Tryptophan metabolism represents an immune checkpoint, and targeting this pathway's rate-limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary of tryptophan in glioblastoma evaluated activity inhibitor GDC-0919, both alone combination with radiation (RT). Experimental Design: LC/GC-MS expression profiling...
T cells of the helper (Th)17 subset offer promise in adoptive T-cell therapy for cancer. However, current protocols ex vivo programming Th17 cells, which include TGFβ exposure, increase expression CD39 and CD73, two cell surface ATP ectonucleotidases that reduce effector functions promote immunosuppression. Here, we report ATP-mediated suppression IFNγ production by can be overcome genetic ablation CD73 or using IL1β instead to program vivo. cultured were also highly polyfunctional,...
To use inhibition of colony-stimulating factor-1 receptor (CSF-1R) to target tumor-associated macrophages (TAMs) and improve the efficacy radiotherapy in glioblastoma (GBM).The CSF-1R inhibitor BLZ-945 was used examine impact on M2 polarization vitro. Using an orthotopic, immunocompetent GBM model, mice were treated with vehicle, RT, BLZ-945, or RT plus BLZ-945.BLZ-945 reduced alone did not median overall survival (mOS=29 days) compared control (mOS=27 days). improved (mOS=45 days; p=0.02),...
Although considerable progress has been made in understanding molecular alterations driving gliomagenesis, the diverse metabolic programs contributing to aggressive phenotype of glioblastoma remain unclear. The aim this study was define and provide context reprogramming gliomagenesis.Integrative cross-platform analyses coupling global metabolomic profiling with genomics patient-derived glioma (low-grade astrocytoma [LGA; n = 28] [n 80]) were performed. Identified then metabolomically,...
Abstract Ex vivo–expanded CD8+ T cells used for adoptive immunotherapy generally acquire an effector memory-like phenotype (TEM cells). With regard to therapeutic applications, two undesired features of this in vivo are limited persistence and reduced antitumor efficacy, relative with a central (TCM Furthermore, there is incomplete knowledge about all the differences between TEM TCM that may influence tumor treatment outcomes. Given survive relatively longer oxidative microenvironments, we...
Glioblastoma (GBM) represents an aggressive and immune-resistant cancer. Preclinical investigations have identified anti-tumor activity of a ketogenic diet (KD) potentially being used to target GBM's glycolytic phenotype. Since immune cells in the microenvironment similar reliance upon nutrients perform their individual functions, we sought determine if KD influenced landscape GBM. Consistent with previous publications, improved survival GBM immune-competent murine model. Immunophenotyping...
Abstract Repetitive stimulation of T-cell receptor (TCR) with cognate antigen results in robust proliferation and expansion the T cells, also imprints them replicative senescence signatures. Our previous studies have shown that life-span antitumor function cells can be enhanced by inhibiting reactive oxygen species (ROS) or intervening ROS-dependent JNK activation leads to its activation-induced cell death. Because tumor suppressor protein p53 is a redox active transcription factor regulates...
To investigate the association of tumour necrosis factor-alpha gene (TNF-alpha) polymorphisms T-1031C, C-863A, and C-857T with bladder cancer risk recurrence after bacille Calmette-Guérin (BCG) immunotherapy, as TNF-alpha regulates inflammatory process influencing susceptibility outcome BCG immunotherapy.In all, 220 patients 206 controls were recruited. Genotyping was done using allele specific-polymerase chain reaction.A CC genotype haplotype -1031C/-863C/-857T showed enhanced to cancer, an...
Glioblastoma represents an archetypal example of a heterogeneous malignancy. To understand the diverse molecular consequences this complex tumor ecology, we analyzed RNA-seq data generated from commonly identified intratumoral structures in glioblastoma enriched using laser capture microdissection. Raw gene-level values fragments per kilobase transcript million reads mapped and associated clinical were acquired publicly available Ivy Atlas Project database MetaboAnalyst (v3.0). The includes...
Glioblastoma is the most common primary malignant brain tumor in adults. Despite aggressive treatment, outcomes remain poor with few long-term survivors. Therefore, considerable effort being made to identify novel therapies for this malignancy. Targeting metabolism represents a promising therapeutic strategy and activation of fatty acid oxidation (FAO) has been identified as central metabolic node contributing toward gliomagenesis. Perhexiline compound long clinical track record angina...
The cellular alterations that give rise to cancer initiate changes in cytokine expression. Though IL-6 is known play a major role proliferation of tumor cells, IL-4 upregulates androgen receptors and prostate-specific antigen (PSA). present study was undertaken evaluate the association gene polymorphisms for susceptibility prostate (PCa) risk. Our included 200 controls histologically confirmed cases PCa. Polymorphisms (intron 3, by VNTR analysis) (-174 G/C, amplification refractory mutation...
XRCC1 protein plays crucial role in base excision repair (BER) by acting as a scaffold for other BER enzymes. Variants gene might alter structure/function or create alternatively spliced influencing efficiency and affect individual susceptibility/recurrence to urinary bladder cancer (BC). We tested whether polymorphisms were associated with BC risk further substantiate of recurrence after Bacillus Calmette-Guerin (BCG) immunotherapy. Genotyping three polymorphic sites at codon Arg194Trp...
What’s known on the subject? and What does study add? Earlier, role of caspases in cancer initiation progression was documented. However, our paper is first to find association caspase gene polymorphism PCa ( CASP 8 ‐652) metastasis 9‐1263 G). Moreover, shows that polymorphisms promoter region can play a major development hormone refectory prostate 8‐652). Results from this pilot may be revaluated, applicable clinical practice. The subjects with presence ‐652 (‐/‐) allele not good for...