A5012954274- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Immunodeficiency and Autoimmune Disorders
- Pediatric health and respiratory diseases
- Eosinophilic Esophagitis
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Viral Infectious Diseases and Gene Expression in Insects
- Single-cell and spatial transcriptomics
- Autoimmune and Inflammatory Disorders Research
- Endometriosis Research and Treatment
- Cancer Immunotherapy and Biomarkers
- Chronic Lymphocytic Leukemia Research
- Cytokine Signaling Pathways and Interactions
- Bipolar Disorder and Treatment
- Nutritional Studies and Diet
- Advancements in Semiconductor Devices and Circuit Design
- Virus-based gene therapy research
- Cardiovascular Health and Risk Factors
- Blood Pressure and Hypertension Studies
- Reproductive System and Pregnancy
- Dermatology and Skin Diseases
- Blood disorders and treatments
University of Pennsylvania
2022-2025
Children's Hospital of Philadelphia
2016-2025
Cancer Research Institute
2023
The Ohio State University
2009-2017
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
2010-2017
Barnes-Jewish Hospital
2015
Beaumont Hospital, Royal Oak
2004
A major limitation of chimeric antigen receptor (CAR) T cell therapies is the poor persistence these cells in vivo
NK cells are the dominant population of immune in endometrium secretory phase menstrual cycle and decidua early pregnancy. The possibility that this is a site cell development particular interest because cyclical death regeneration during cycle. To investigate this, we searched for developmental stages 1-4, based on expression CD34, CD117, CD94. In study, report heterogeneous stage 3 precursor (CD34(-)CD117(+)CD94(-)) mature 4 (CD34(-)CD117(-/+)CD94(+)) cells, but not multipotent 1 2...
Accumulating evidence indicates that human natural killer (NK) cells develop in secondary lymphoid tissue (SLT) through a so-called "stage 3" developmental intermediate minimally characterized by CD34(-)CD117(+)CD94(-) immunophenotype lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate (ILC) types include interleukin-1 receptor (IL-1R1)-positive, IL-22-producing ILC3s. Whether ILC3s are developmentally related to...
The development of a broad repertoire T cells, which is essential for effective immune function, occurs in the thymus. Although some data suggest that cell can occur extrathymically, many researchers remain skeptical extrathymic has an important role generating healthy individuals. However, it may be setting poor thymic function or congenital deficit and context autoimmunity, cancer, regenerative medicine. Here, we report evidence stepwise program within human tonsil. We identified 5...
Abstract Group 3 innate lymphoid cells (ILC3s) are important regulators of the immune system, maintaining homeostasis in presence commensal bacteria, but activating defenses response to microbial pathogens. ILC3s a robust source IL-22, cytokine critical for stimulating antimicrobial response. We sought identify cytokines that can promote proliferation and induce or maintain IL-22 production by determine molecular mechanism this process. identified IL-18 as cooperates with an ILC3 survival...
Background Relapse of B-cell acute lymphoblastic leukemia (B-ALL) with CD19-antigen loss after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has a dismal prognosis. Novel immunotherapeutic strategies for this patient population are urgently needed. Methods We tested novel, fully human anti-CD22/4-1BB CAR construct, CART22-65s, in parallel phase I studies pediatric and adult B-ALL. After lymphodepletion, CART22-65s was infused using 3-day fractionated dosing scheme, allowing...
In chronic infections, the immune response fails to control virus, leading persistent antigen stimulation and progressive development of T cell exhaustion. effector differentiation is poorly understood in context exhaustion, but targeting programs may provide new strategies for reinvigorating function. We identified Tribbles pseudokinase 1 (Trib1) as a central regulator antiviral immunity, where loss Trib1 led sustained enrichment effector-like KLRG1+ cells, enhanced function, improved viral...
Abstract Sorafenib is an oral multikinase inhibitor that was originally developed as a Raf kinase inhibitor. We hypothesized sorafenib would also have inhibitory effects on cytokine signaling pathways in immune cells. PBMCs from normal donors were treated with varying concentrations of and stimulated IFN-α or IL-2. Phosphorylation STAT1 STAT5 measured by flow cytometry confirmed immunoblot analysis. Changes IFN-α– IL-2–stimulated gene expression quantitative PCR, changes production evaluated...
CD8+ T cell exhaustion (TEX) impairs the ability of cells to clear chronic infection or cancer. While TEX are hypofunctional, some retain effector gene signatures, a feature associated with killer lectin-like receptor (KLR) expression. Although KLR+ (TKLR) may improve control antigen, signaling molecules regulating this population poorly understood. Using single-cell RNA sequencing (scRNA-seq), flow cytometry, velocity, and (scTCR-seq), we demonstrate that deleting pseudokinase Trib1 shifts...
Primary Immunodeficiency Diseases (PID) are a group of rare genetic disorders characterized by severe deficiency in immune function. These deficiencies result from abnormal differentiation, maturation, or activation specific cells, and can involve humoral, cellular complement-mediated immunity [1]. Typical presentation involves recurrent persistent infections, autoimmune-type reactions, some cases malignancy [2]. To date, more than 95 classified as PID Early detection is paramount,...
T cell exhaustion (T EX ) impairs the ability of cells to clear chronic infection or cancer. While exhausted are hypofunctional, some retain effector gene signatures, a feature that is associated with expression KLRs (killer lectin-like receptors). Although KLR + may improve control antigen, signaling molecules regulating this population poorly understood. Using scRNA-seq, flow cytometry, RNA velocity, and scTCR-seq, we demonstrate deleting pseudokinase Trib1 shifts towards CX3CR1...