A5030384546- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune cells in cancer
- Ion Transport and Channel Regulation
- Atherosclerosis and Cardiovascular Diseases
- Renal Transplantation Outcomes and Treatments
- Complement system in diseases
- Electrolyte and hormonal disorders
- Cytomegalovirus and herpesvirus research
- RNA Interference and Gene Delivery
- Adenosine and Purinergic Signaling
- Glioma Diagnosis and Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Immunodeficiency and Autoimmune Disorders
- Gut microbiota and health
- Sphingolipid Metabolism and Signaling
- Transplantation: Methods and Outcomes
- Clostridium difficile and Clostridium perfringens research
- Mathematical Biology Tumor Growth
- Membrane-based Ion Separation Techniques
- Macrophage Migration Inhibitory Factor
- Cancer Research and Treatments
Cleveland Clinic
2016-2025
Cleveland Clinic Lerner College of Medicine
2019-2024
Cerner (United States)
2024
Case Western Reserve University
2024
Abstract Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, emerging evidence suggests that these extend to genetic/epigenetic cellular differences, including immune responses. However, the mechanisms driving immunologic sex not fully understood. Here, we demonstrate T cells play a critical role GBM differences. Male mice exhibited accelerated tumor growth, with decreased frequency increased exhaustion of CD8+ tumor. Furthermore, higher progenitor exhausted was...
Lymphocyte activation gene-3 (LAG3) is a coinhibitory receptor expressed by various immune cells. While immunomodulatory potential of LAG3 being explored in cancer and autoimmunity, there no information on its role following organ transplantation. Our study investigated the functions mouse model renal allograft rejection. LAG3-/- recipients rapidly reject MHC-mismatched allografts that are spontaneously accepted WT recipients, with graft histology characteristic antibody mediated rejection...
Prolonged cold ischemia storage (CIS) is a leading risk factor for poor transplant outcome. Existing strategies strive to minimize ischemia-reperfusion injury in transplanted organs, yet there need novel approaches improve outcomes of marginal allografts and expand the pool donor organs suitable transplantation. Aquaporins (AQPs) are family water channels that facilitate homeostasis, tissue injury, inflammation. We tested whether inhibition AQP4 improves survival fully MHC-mismatched murine...
Abstract Aquaporins (AQPs) are water channels that mediate a variety of biological processes. However, their role in the immune system is poorly understood. We recently reported AQP4 expressed by naïve and memory T cells blockade with small molecule inhibitor prolongs murine heart allograft survival at least partially through diminishing cell activation, proliferation trafficking. The goal this study was to determine how function impacts absence antigen stimulation. inhibition transiently...
Antibody-mediated lymphoablation is used in solid organ and stem cell transplantation autoimmunity. Using murine anti-thymocyte globulin (mATG) a mouse model of heart transplantation, we previously reported that the homeostatic recovery CD8+ T cells requires help from depletion-resistant memory CD4+ delivered through CD40-expressing B cells. This study investigated mechanisms by which mediate proliferation lymphopenic hosts. While required MHC class I expression host, reconstitution occurred...
Abstract Staphylococcal superantigens induce massive activation of T cells and inflammation, leading to toxic shock syndrome. Paradoxically, increasing evidence indicates that can also immunosuppression by promoting regulatory cell (Treg) development. In this study, we demonstrate stimulation strength plays a critical role in superantigen-mediated induction immunosuppressive human CD4+CD25+FOXP3+ cells. Suboptimal low dose (1 ng/ml) staphylococcal enterotoxin C1 (SEC1) led de novo generation...
Abstract Aquaporins are a family of ubiquitously expressed transmembrane water channels implicated in broad range physiological functions. We have previously reported that aquaporin 4 (AQP4) is on T cells and treatment with small molecule AQP4 inhibitor significantly delays cell mediated heart allograft rejection. Using either genetic deletion or inhibitor, we show supports receptor activation both mouse human cells. Intact required for optimal (TCR)-related signaling events, including...
Abstract Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, emerging evidence suggests that these extend to genetic/epigenetic cellular differences, including immune responses. However, the mechanisms driving immunological sex not fully understood. Using GBM models, we demonstrate T cells play a critical role differences. Male mice exhibited accelerated tumor growth, with decreased cell infiltration increased exhaustion. Furthermore, higher frequency of...
Abstract Many cancers, including glioblastoma (GBM), have a male-biased sex difference in incidence and outcome. The underlying reasons for this bias are unclear but likely involve differences tumor cell state immune response. This effect is further amplified by hormones, androgens, which been shown to inhibit anti-tumor T immunity. Here, we show that androgens drive immunity brain tumors, contrast its other types. Upon castration, growth was accelerated with attenuated function GBM models,...
<p>Supplementary Fig. S1. Immune cell-dependent survival differences between males and females in murine glioblastoma models. Supplementary S2. Mouse syngeneic GBM cell lines do not contain a Y chromosome. S3. Frequencies of tumor-infiltrating immune cells SB28 model. S4. Sex difference SB28-OVA model GL261 S5. No sex T was observed at an earlier time point. S6. Male are more exhausted the S7. Phenotype periphery does replicate shown cells. S8. subsets. S9. PD1 blockade enhanced...
<p>Supplementary Fig. S1. Immune cell-dependent survival differences between males and females in murine glioblastoma models. Supplementary S2. Mouse syngeneic GBM cell lines do not contain a Y chromosome. S3. Frequencies of tumor-infiltrating immune cells SB28 model. S4. Sex difference SB28-OVA model GL261 S5. No sex T was observed at an earlier time point. S6. Male are more exhausted the S7. Phenotype periphery does replicate shown cells. S8. subsets. S9. PD1 blockade enhanced...
Abstract Lymphocyte activation gene-3 (LAG3) is a coinhibitory receptor expressed by range of immune cells. The immunomodulatory potential LAG3 being explored in cancer and autoimmunity fields but not transplantation. Using our mouse kidney transplant models we sought to address the role graft rejection. Untransplanted LAG3-/- mice have elevated heterologous immunity against panel alloantigens. Recipient deficiency results rapid rejection MHC-mismatched renal allografts that are...
Abstract After transplant recipient treatment with anti-thymocyte globulin (ATG), B cells recover and drive reconstitution of depletion-resistant memory T cells. This study investigated the effects ATG depletion on in recipients. Experimental groups were: 1) BALB/c to B6 heart Tx; 2) Tx + ATG; 3) alone; 4) naïve B6. Spleen were isolated d. 8 posttransplant analyzed by single cell RNA-seq. Across all subsets, immune stimulatory genes including lymphotoxin A B, MHC-related costimulatory...
Abstract Lymphocyte activation gene-3 (LAG3) is a coinhibitory receptor expressed by range of immune cells. While immunomodulatory potential LAG3 being actively explored in cancer and autoimmunity fields, there no information on how this pathway affects alloreactive responses following organ transplantation. The goal study was to investigate the functions recipient mouse model renal allograft rejection. We found that mice deficient expression have elevated heterologous immunity against panel...
Abstract The role of lymphocyte activation gene-3 (LAG3) in T cell functions is well studied, however its humoral immune responses remains poorly characterized. goal this study was to test the recipient LAG3 a mouse model renal allograft rejectionNaive B6.LAG3−/− mice have elevated numbers follicular and memory cells, plasma cells compared WT mice, as increased frequencies reactive H-2Dd, H-2Ds, H-2Dq H-2Dk alloantigens. When kidneys were transplanted from C3H donors B6 LAG3−/− all kidney...
<div>Abstract<p>Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, emerging evidence suggests that these extend to genetic/epigenetic cellular differences, including immune responses. However, the mechanisms driving immunologic sex not fully understood. Here, we demonstrate T cells play a critical role GBM differences. Male mice exhibited accelerated tumor growth, with decreased frequency increased exhaustion of CD8<sup>+</sup> tumor....