A5047220660- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Immune Cell Function and Interaction
- Cellular Mechanics and Interactions
- Viral Infectious Diseases and Gene Expression in Insects
- Autophagy in Disease and Therapy
- Cellular transport and secretion
- X-ray Spectroscopy and Fluorescence Analysis
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Virus-based gene therapy research
- Nanowire Synthesis and Applications
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Prostate Cancer Diagnosis and Treatment
- 3D Printing in Biomedical Research
- Prostate Cancer Treatment and Research
- MicroRNA in disease regulation
- Immunotherapy and Immune Responses
- Cancer Research and Treatments
- Hippo pathway signaling and YAP/TAZ
- CRISPR and Genetic Engineering
UPMC Hillman Cancer Center
2022-2025
University of Pittsburgh
2023-2024
Virginia Commonwealth University
2016-2018
Abstract CD8 + T cells are critical mediators of antitumor immunity but differentiate into a dysfunctional state, known as cell exhaustion, after persistent receptor stimulation in the tumor microenvironment (TME). Exhausted (T ex ) characterized by upregulation coinhibitory molecules and reduced polyfunctionality. TME experience an immunosuppressive metabolic environment via levels nutrients oxygen buildup lactic acid. Here we show that terminally uniquely upregulate Slc16a11 , which...
Cellular immunotherapies for cancer represent a means by which patient's immune system can be augmented with high numbers of tumor-specific T cells. Chimeric antigen receptor (CAR) therapy involves genetic engineering to 'redirect' peripheral cells tumor targets, showing remarkable potency in blood cancers. However, due several resistance mechanisms, CAR-T cell therapies remain ineffective solid tumors. We and others have shown the microenvironment harbors distinct metabolic landscape that...
// Hussein F. Aqbi 1 , Liliya Tyutyunyk-Massey 2 Rebecca C. Keim 1, 3 Savannah E. Butler Theresa Thekkudan Supriya Joshi 4 Timothy M. Smith Dipankar Bandyopadhyay 3, 5 Michael O. Idowu 6 Harry D. Bear 7 Kyle K. Payne 8 David A. Gewirtz 2, and Masoud H. Manjili 6, 9 Department of Microbiology Immunology, Virginia Commonwealth University School Medicine, Richmond, 23298, VA, USA Pharmacology Toxicology, Massey Cancer Center, Human Molecular Genetics, Biostatistics, Pathology, Surgery, Moffitt...
Vesicle trafficking regulates epithelial cell migration by remodeling matrix adhesions and delivering signaling molecules to the migrating leading edge. Membrane fusion, which is driven soluble N-ethylmaleimide-sensitive factor associated receptor (SNARE) proteins, an essential step of vesicle trafficking. Mammalian SNAREs represent a large group but few have been implicated in regulation migration. Ykt6 unique SNARE existing equilibrium between active membrane-bound inactive cytoplasmic...
The modeling of chimeric antigen receptor (CAR) T cell therapies has been mostly focused on immunodeficient models. However, there are many advantages in studying CAR-T biology an immunocompetent setting. We generated a fully murine CAR targeting CD105 (endoglin), component the TGFβ expressed surface certain solid tumors and acute leukemias. CD105-targeted cells can be grown from various backgrounds, tracked vivo by congenic marks, activated isolation or tumor cells. were toxic at higher...
<h3>Background</h3> Adoptive cell therapy (ACT) is a cancer treatment in which T cells are isolated from patient, enriching or engineering tumor specificity, and expanding the prior to transferring them back into patient. While these therapies have shown remarkable success some cancers, many cancers no response relapses common. we made major advances receptors, culture expansion steps use media formulations that contain hyperphysiologic concentrations of nutrients, most notably glucose. We...
Abstract Proliferative recovery in tumor cells subsequent to chemotherapy and/or radiation-induced prolonged growth arrest may prove represent a state of autophagy senescence. This also be useful as an vitro model dormancy. To explore this hypothesis, studies were performed primary mouse mammary carcinoma (MMC) treated with Adriamycin (ADR) (0.25uM - 1uM) for 3 days (2h each) and ionizing radiation (IR) (6Gy). Promotion was confirmed based on detection autophagosomes acridine orange...
Epithelial cell migration is a key regulatory element of variety biological and pathological processes, including embryonic morphogenesis, tissue repair, tumor metastasis. This multistage process involving epithelial adhesion to the extracellular matrix (ECM) remodeling cortical cytoskeleton. Trafficking ECM proteins other membrane signaling migrating cellular edge plays an essential role in regulating motility. YKT6 component vesicle fusion machinery that regulates ER‐Golgi trafficking,...
<h3>Background</h3> Adoptive cell therapies, like chimeric antigen receptor (CAR) T therapy act by redirecting and enhancing a patient's immune response to tumor cells, with success in hematologic malignancies. However, many patients relapse due failure of persistence cells. Further, efficacy cellular therapies is limited barriers poor infiltration an immunosuppressive microenvironment. In addition, generating required numbers limiting factor CAR production, leading the development...