A5041139369- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Immune cells in cancer
- Cancer Research and Treatments
- melanin and skin pigmentation
- Cancer Mechanisms and Therapy
- Cytomegalovirus and herpesvirus research
- Sphingolipid Metabolism and Signaling
- Virus-based gene therapy research
- Adenosine and Purinergic Signaling
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Phagocytosis and Immune Regulation
- Synthesis and Biological Evaluation
- Cancer, Hypoxia, and Metabolism
- Atherosclerosis and Cardiovascular Diseases
- Peptidase Inhibition and Analysis
- SARS-CoV-2 and COVID-19 Research
- Glycosylation and Glycoproteins Research
- Hematopoietic Stem Cell Transplantation
- Calcium signaling and nucleotide metabolism
- Quinazolinone synthesis and applications
Medical University of South Carolina
2016-2025
MUSC Hollings Cancer Center
2015-2024
University of South Carolina
2016-2024
College of Charleston
2015
UConn Health
2003-2009
University of Connecticut
2003-2006
Sanjay Gandhi Post Graduate Institute of Medical Sciences
1999-2003
University of Nebraska Medical Center
1992
Abstract Understanding the intrinsic mediators that render CD8 + T cells dysfunctional in tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report C/EBP homologous protein (Chop), downstream sensor of severe endoplasmic reticulum (ER) stress, major negative regulator effector function tumor-reactive cells. Chop expression increased tumor-infiltrating cells, which correlates with poor clinical outcome ovarian patients. Deletion improves...
Dendritic cells (DCs) enhance the quality of anti-tumor immune response in patients with cancer. Thus, we posit that DC-based immunotherapy, conjunction toll-like receptor (TLR)-3 agonist poly-ICLC, is a promising approach for harnessing immunity against metastatic or locally advanced unresectable pancreatic cancer (PC). We generated autologous DCs from peripheral blood HLA-A2+ PC. were pulsed three distinct A2-restricted peptides: 1) human telomerase reverse transcriptase (hTERT, TERT572Y),...
Vitiligo can be reversed through immune targeting with mutant heat shock protein 70.
Alloreactive donor T cells are the driving force in induction of graft-versus-host disease (GVHD), yet little is known about cell metabolism response to alloantigens after hematopoietic transplantation (HCT). Here, we have demonstrated that undergo metabolic reprograming allogeneic HCT. Specifically, employed a murine BM transplant model and determined switch from fatty acid β-oxidation (FAO) pyruvate oxidation via tricarboxylic (TCA) cycle aerobic glycolysis, thereby increasing dependence...
Sphingosine 1-phosphate (S1P), a bioactive lysophospholipid generated by sphingosine kinase 1 (SphK1), regulates lymphocyte egress into circulation via S1P receptor (S1PR1) signaling, and it controls the differentiation of regulatory T cells (Tregs) helper-17 cells. However, mechanisms which receptor-independent SphK1-mediated intracellular levels modulate cell functionality remains unknown. We show here that SphK1-deficient maintain central memory phenotype exhibit higher mitochondrial...
We lack a mechanistic understanding of aging-mediated changes in mitochondrial bioenergetics and lipid metabolism that affect T cell function. The bioactive sphingolipid ceramide, induced by aging stress, mediates mitophagy death; however, the aging-related roles ceramide regulating function remain unknown. Here, we show activated cells isolated from mice have elevated C14/C16 accumulation mitochondria, generated synthase 6, leading to mitophagy/mitochondrial dysfunction. Mechanistically,...
Trastuzumab emtansine (T-DM1) was the first and one of most successful antibody-drug conjugates (ADC) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells, T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form death. The payload mediated ICD by inducing eIF2α...
Abstract Although adoptive transfer of autologous tumor antigen–specific T-cell immunotherapy can produce remarkable clinical efficacy, most patients do not achieve durable complete responses. We hypothesized that reducing susceptibility T cells to activation-induced cell death (AICD), which increases during the rapid in vitro expansion therapeutic before their infusion, might improve persistence adoptively transferred cells. Our investigations revealed repetitive stimulation receptor (TCR)...
Vitiligo is an autoimmune skin disease characterized by melanocyte destruction. Regulatory T cells (Tregs) are greatly reduced in vitiligo skin, and replenishing peripheral Tregs can provide protection against depigmentation. Ganglioside D3 (GD3) overexpressed perilesional epidermal cells, including melanocytes, which prompted us to generate GD3-reactive chimeric antigen receptor (CAR) treat vitiligo. Mice received either untransduced or GD3-specific test the hypothesis that specificity...
Mitochondria and endoplasmic reticulum (ER) share structural functional networks activate well-orchestrated signaling processes to shape cells' fate function. While persistent ER stress (ERS) response leads mitochondrial collapse, moderate ERS promotes Strategies boost antitumor T-cell function by targeting ER-mitochondria cross-talk have not yet been exploited. Here, we used carbon monoxide (CO), a short-lived gaseous molecule, test whether engaging conditions can improve functions in T...
Abstract Effector CD8+ T cells rely primarily on glucose metabolism to meet their biosynthetic and functional needs. However, nutritional limitations in the tumor microenvironment can cause T-cell hyporesponsiveness. Therefore, must acquire metabolic traits enabling sustained effector function at site elicit a robust antitumor immune response. Here, we report that IL12-stimulated have elevated intracellular acetyl CoA levels maintain IFNγ nutrient-deprived, tumor-conditioned media (TCM)....