A5026562880- Immune Cell Function and Interaction
- Histone Deacetylase Inhibitors Research
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Glioma Diagnosis and Treatment
- T-cell and B-cell Immunology
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Spectroscopy and Laser Applications
- Inorganic Fluorides and Related Compounds
- Atomic and Subatomic Physics Research
- Cancer, Hypoxia, and Metabolism
- Prostate Cancer Treatment and Research
- Chromatin Remodeling and Cancer
- Atmospheric Ozone and Climate
- Cancer-related molecular mechanisms research
The University of Texas MD Anderson Cancer Center
2018-2025
Moffitt Cancer Center
2023-2025
University of South Florida
2023-2025
Significance Expression and regulation of IL-15 in the tumor microenvironment are poorly understood important as studies have provided correlative data that expression within human tumors is a critical factor dictating antitumor responses. Moreover, utilizes unique mechanisms preclude typical analyses. Herein we demonstrate using multiple models soluble (s) IL-15/IL-15Rα complexes expressed regulate tumor-infiltrating lymphocyte numbers. While levels sIL-15 low established tumors,...
Diffuse midline gliomas (DMG), including brainstem diffuse intrinsic pontine glioma (DIPG), are incurable pediatric high-grade (pHGG). Mutations in the H3 histone tail (H3.1/3.3-K27M) a feature of DIPG, rendering them therapeutically sensitive to small-molecule inhibition chromatin modifiers. Pharmacological lysine-specific demethylase 1 (LSD1) is clinically relevant but has not been carefully investigated pHGG or DIPG.Patient-derived DIPG cell lines, orthotopic mouse models, and datasets...
CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the of NK surveillance acute myeloid leukemia (AML). cells patients AML had lower expression CD226. CRISPR-Cas9 deletion led reduced LFA-1 recruitment, poor decreased anti-leukemic activity. Engineering express chimeric antigen receptor targeting CD38 (CAR38) could...
Cell therapies such as chimeric-antigen receptor (CAR) T-cells and NK cells are cutting-edge methods for treating cancer other diseases. There is high interest in optimizing drug treatment regimens to best work together with emerging cell therapies, targeting epigenetic enzymes stimulate recognition of tumor by immune cells. Herein we uncover new mechanisms the histone demethylase LSD1, various inhibitors unique domains function grown therapy. Catalytic (tranylcypromine structural...
NKTR-255 is a PEG conjugate of recombinant human IL-15 (rhIL-15) being examined as potential cancer immunotherapeutic. Since responses can be mediated by trans or cis presentation via IL-15Rα soluble IL-15/IL-15Rα complexes, we investigated the role in driving using defined naive and memory OVA-specific CD8+ T cells (OT-I) NK mice. induced 2.5- 2.0-fold expansion cells, respectively, WT In adoptive transfer studies, proliferation OT-I response to was not impaired IL-15Rα−/− mice, suggesting...
Abstract Clinical relapse and metastases are the major causes of death in melanoma. Currently, adoptive T cell therapy using tumor-infiltrating lymphocytes rich cytotoxic CD8+ cells (CTLs) is one promising approaches that helps overcome this challenge melanoma; however CTL transfer alone does not improve clinical response suggesting a role helper CD4+ cells. Recently, it has been noted infiltration subset, named as follicular (Tfh) into tumor sites correlates with increased survival cancer...
Vibrational relaxation in the A 1 B and a 3 excited electronic states of sulfur dioxide vapor has been observed by direct spectroscopic means. The effects vibrational on phosphorescence quantum yield have investigated pressure range from 0.6 to 200 mTorr pure mixtures with He, N 2 , CO SF 6 . Phosphorescence persists at lowest reached for excitation 302.0 or 313.1 nm, contrary previous reports. mechanism production wide bandwidth used here (185–370 cm −1 ) is consistent recent evidence two...
Improved therapies for glioblastoma (GBM) are desperately needed and require preclinical evaluation in models that capture tumor heterogeneity intrinsic resistance seen patients. Epigenetic alterations have been well documented GBM lysine-specific demethylase 1 (LSD1/KDM1A) is amongst the chromatin modifiers implicated stem cell maintenance, growth differentiation. Pharmacological inhibition of LSD1 clinically relevant, with numerous compounds various phases clinical development, but an...
Abstract High grade gliomas (HGG) carry poor prognosis with median survival rates under 15 months post diagnosis. Due to dysregulation of kinase signaling pathways within these tumors, targeted inhibition has been considered as a promising clinical strategy. However in HGG, many single-agent inhibitors EGFR or PI3K have shown limited response due activation compensatory signaling. Single-molecule multikinase may decrease resistance, present single pharmacokinetic dosage profile, and reduce...
Abstract Inhibitors of histone deacetylases (HDACi) have been tested in glioblastoma (GBM), however, single agent clinical efficacy has not proven, prompting study combinatorial approaches. A rational HDACi combination strategy is with inhibition LSD1, lysine specific demethylase 1, a known to exist complex HDAC1/2. We previously showed vivo combining brain permeant LSD1 inhibitor, tranylcypromine (TCP) together vorinostat. More selective inhibitors developed and were the current HDACi,...
Epigenetically directed cancer therapeutics, such as targeting the histone demethylase LSD1, are an emerging approach to treatment of glioblastoma (GBM), with dozens candidates in preclinical development. To date, knockdown (KD) LSD1 exerts effects on proliferation, but evaluation and comparison pharmacological inhibitors GBM is lacking. Therefore, present study evaluated effect KD compared inhibition studied four patient derived GSCs vitroand vivo for therapeutic efficacy genes associated...