A5004858116- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Cancer Mechanisms and Therapy
- Immune cells in cancer
- Macrophage Migration Inhibitory Factor
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Cancer Immunotherapy and Biomarkers
- Heparin-Induced Thrombocytopenia and Thrombosis
- Platelet Disorders and Treatments
- Immune Response and Inflammation
- Transgenic Plants and Applications
- Venous Thromboembolism Diagnosis and Management
- Pancreatic function and diabetes
- CRISPR and Genetic Engineering
- Cancer therapeutics and mechanisms
- Sphingolipid Metabolism and Signaling
- Cancer Cells and Metastasis
- Probiotics and Fermented Foods
- Extracellular vesicles in disease
- Malaria Research and Control
Medical College of Wisconsin
2019-2024
Versiti Blood Center of Wisconsin
2019-2023
University of California, Los Angeles
2015-2019
UCLA Jonsson Comprehensive Cancer Center
2017
Although recent evidence demonstrates heterogeneity among CD8+ T cells during chronic infection, developmental relationships and mechanisms underlying their fate decisions remain incompletely understood. Using single-cell RNA TCR sequencing, we traced the clonal expansion differentiation of LCMV infection. We identified immense phenotypic diversity, including a subset termed intermediate cells. Trajectory analyses infection models showed arise from progenitor before bifurcating into terminal...
Abstract SPHK1 (sphingosine kinase‐1) catalyzes the phosphorylation of sphingosine to sphingosine‐1‐phosphate (S1P), is found be highly expressed in solid tumors. Here, extracellular vesicles (EVs) are identified as key transporters tumor microenvironment. Consequently, SPHK1‐packaged EVs elevate S1P levels microenvironment, where appears an immunosuppressive agent. However, exact mechanism how mediates its effects cancer not understood. It investigated that can induce T cell exhaustion....
Natural Killer (NK) cells target oral, pancreatic, lung, breast, glioblastoma and melanoma stem-like/poorly differentiated tumors. Differentiation of the abovementioned tumors with supernatants from split-anergized NK decreases their susceptibility to cells, but increases sensitivity cisplatin (CDDP)-mediated cell death. Breast tumor CD44 knockdown display enhanced cell-mediated lysis, potentially due decreased differentiation. We also demonstrate that sulindac, a non-steroidal...
Natural killer (NK) cells are known to target cancer stem and undifferentiated tumors. In this paper, we provide a novel strategy for expanding large numbers of super-charged NK with significant potential lyse differentiate demonstrate the differences in dynamics cell expansion between healthy donors patients. Decline cytotoxicity lower interferon (IFN)-γ secretion by osteoclast (OC)-expanded from patients correlates faster residual contaminating T within purified cells, whereas donors' OCs...
Abstract Influenza virus infection causes increased morbidity and mortality in the elderly. Aging impairs immune response to influenza, both intrinsically because of altered interactions with endothelial pulmonary epithelial cells. To characterize these changes, we performed single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk (bulk RNA-seq) on lung tissue from young aged female mice at days 0, 3, 9 post-influenza infection. Our analyses identified dozens key genes...
Our previous reports demonstrated that the magnitude of NK cell mediated cytotoxicity correlated directly with stage and levels differentiation tumor cells. In addition, we have shown previously activated cells induce growth inhibition cancer through induction resulting in resistance to secreted cytokines, as well direct NK-tumor contact. this report show comparison IL-2+anti-CD16mAb treated cells, activation by probiotic bacteria sAJ2 combination IL-2 anti-CD16mAb substantially decreases...
Therapeutic role of NK cells in solid tumors was challenged previously even though their hematological malignancies has clearly been established. Furthermore, functions and numbers are greatly suppressed oral cancer patients necessitating effective future immunotherapeutic strategies to aid the control disease. The humanized-BLT (hu-BLT) mice were used implant stem-like/undifferentiated study super-charged with without feeding AJ2 probiotic bacteria. Implanted CSC/undifferentiated resected...
Background and Aims: We have previously demonstrated that the stage of differentiation tumors has profound effect on function NK cells, stem-like/poorly differentiated were preferentially targeted by cells. Therefore, in this study we determined role super-charged cells immune mobilization, lysis, stem-like/undifferentiated implanted pancreas humanized-BLT (hu-BLT) mice fed with or without AJ2 probiotics. The phenotype, growth rate metastatic potential pancreatic (NK-differentiated) patient...
There is a strong correlation between myeloid-derived suppressor cells (MDSC) and resistance to immune checkpoint blockade (ICB), but the detailed mechanisms underlying this are largely unknown. Using single-cell RNA sequencing analysis in bilateral tumor model, we found that immunosuppressive myeloid with characteristics of fatty acid oxidative metabolism dominate immune-cell landscape ICB-resistant subjects. In addition, uncovered previously underappreciated role serine/threonine kinase,...
Abstract The FDA-approved prophylactic antimalarial drug atovaquone (ATO) recently was repurposed as an antitumor drug. Studies show that ATO exerts a profound antiproliferative effect in several cancer cells, including breast, ovarian, and glioma. Analogous to the mechanism of action proposed parasites, inhibits mitochondrial complex III cell respiration. To enhance chemotherapeutic efficacy oxidative phosphorylation inhibition, we developed mitochondria-targeted...
During acute infections, CD8+ T cells form various memory subpopulations to provide long-lasting protection against reinfection. central (TCM), effector (TEM), and long-lived (LLE) are circulating populations with distinct plasticity, migration patterns, functions. Tissue-resident (TRM) permanently reside in the frontline sites of pathogen entry tissue-specific upon Here, using single-cell RNA-sequencing (scRNA-seq) bulk RNA-seq, we examined different shared transcriptomes regulators TRM...
The combined/synergistic effect of genetic mutation KRAS in the pancreas and obesity, a life-style factor on suppression NK cells at pre-neoplastic stage pancreatic cancer is not yet investigated subject this report. Obese mice with (KC) fed high fat calorie diet (HFCD) exhibit severe deficiencies cell expansion function cancer. Decreased cell-mediated cytotoxicity observed peripheral blood, spleen, peri-pancreatic-adipose tissue obese KC mice, whereas bone marrow an increased when compared...
In cancer, CD8+ T cells enter a dysfunctional state which prevents them from effectively targeting and killing tumor cells. Tumor-infiltrating consist of heterogeneous population memory-like progenitor, effector, terminally exhausted that exhibit differing functional self-renewal capacities. Our recently published work has shown interleukin (IL)-21-producing CD4+ help to generate effector within the tumor, results in enhanced control. However, molecular mechanisms by helper regulate...
Hydroxyurea (HU), an FDA-approved drug for treating sickle cell disease, is used as antitumor alone and together with conventional chemotherapeutics or radiation therapy. HU primarily to treat myeloproliferative diseases because it inhibits the enzyme ribonucleotide reductase involved in DNA synthesis. The hydroxyl group considered critical its antiproliferative chemotherapeutic effects. Here, we substituted a triphenylphosphonium cation attached alkyl different chain lengths, forming new...
The list of genes, which augment NK cell function when knocked out in neighboring cells is increasing, and may point to the fundamental targeting with diminished capability differentiate optimally since are able target less differentiated cells, aid their differentiation. In this paper, we aimed at understanding effect monocytes from targeted knockout COX-2 myeloid (Cox-2(flox/flox);LysM(Cre/) (+)) control littermates (Cox-2(flox/flox);LysM (+) (/) on ex vivo cells. Furthermore, compared...
Abstract Loss of target antigens in tumor cells has become one the major hurdles limiting efficacy adoptive cell therapy (ACT)–based immunotherapies. The optimal approach to overcome this challenge includes broadening immune response from initially targeted tumor-associated antigen (TAA) other TAAs expressed tumor. To induce a more broadly antitumor response, we utilized our previously developed Re-energized ACT (ReACT), which capitalizes on synergistic effect pathogen-based immunotherapy...
Severe COVID-19 is associated with unprecedented thromboembolic complications. We found that hospitalized patients develop immunoglobulin Gs (IgGs) recognize a complex consisting of platelet factor 4 and heparin similar to those developed in heparin-induced thrombocytopenia thrombosis (HIT), however, independent exposure. These antibodies activate platelets the presence TLR9 stimuli, stimuli are prominent COVID-19. Strikingly, out 42 cloned from IgG1+ RBD-binding B cells could platelets....
<div>Abstract<p>There is a strong correlation between myeloid-derived suppressor cells (MDSC) and resistance to immune checkpoint blockade (ICB), but the detailed mechanisms underlying this are largely unknown. Using single-cell RNA sequencing analysis in bilateral tumor model, we found that immunosuppressive myeloid with characteristics of fatty acid oxidative metabolism dominate immune-cell landscape ICB-resistant subjects. In addition, uncovered previously underappreciated...