A5103148930- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Organ Transplantation Techniques and Outcomes
- Renal Transplantation Outcomes and Treatments
- CAR-T cell therapy research
- Liver Disease Diagnosis and Treatment
- Liver Disease and Transplantation
- Signaling Pathways in Disease
- Hematopoietic Stem Cell Transplantation
- PI3K/AKT/mTOR signaling in cancer
- Hepatocellular Carcinoma Treatment and Prognosis
- Cardiac, Anesthesia and Surgical Outcomes
- Bariatric Surgery and Outcomes
- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Parkinson's Disease Mechanisms and Treatments
- Abdominal Trauma and Injuries
- Monoclonal and Polyclonal Antibodies Research
- Genetic and Kidney Cyst Diseases
- Chronic Lymphocytic Leukemia Research
- Cytokine Signaling Pathways and Interactions
- Pancreatic and Hepatic Oncology Research
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
University of Kentucky
2015-2024
Markey Cancer Center
2019-2024
University of Kent
2021
Albert B. Chandler Hospital
2012
University of Michigan–Ann Arbor
2003-2009
Bipar
2006
Hospital for Special Surgery
1998-2005
Cornell University
1998-2003
UCL Australia
2000
Memorial Sloan Kettering Cancer Center
1998
Abstract TCR and CD28 costimulatory receptor-cooperative induction of T cell IL-2 secretion is dependent upon activation mitogen-activated protein (MAP) kinases. Using yeast-hybrid technology, we cloned a novel cytoplasmic tail (CD28 CYT) interacting protein, MAP kinase phosphatase-6 (MKP6), which demonstrate inactivates Several lines evidence indicate that MKP6 plays an important functional role in signaling. First, human peripheral blood cells (PBT), expression strongly up-regulated by...
Background Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central peripheral inflammation, a major secondary initiated by event, has been implicated potentiation nociceptive pain. We hypothesized that inflammatory response to diffuse potentiates persistent through prolonged immune dysregulation. Results To test this, adult, male C57BL/6 mice were subjected midline fluid percussion or sham procedure. One cohort was analyzed...
Autophagy targets cellular components for lysosomal-dependent degradation in which the products of may be recycled protein synthesis and utilized energy production. also plays a critical role cell homeostasis regulation many physiological pathological processes prompts this investigation new agents to effect abnormal autophagy hepatocellular carcinoma (HCC). 2,5-Dichloro-N-(2-methyl-4-nitrophenyl) benzenesulfonamide (FH535) is synthetic inhibitor Wnt/β-catenin pathway that exhibits...
T cell–specific adaptor protein (TSAd) is a lineage–restricted signaling molecule that thought to participate in the assembly of intracellular complexes cells. Previous studies TSAd-deficient mice have revealed role for TSAd induction cell interleukin 2 secretion and proliferation. We now show are susceptible lupus-like autoimmune disease. On nonautoimmune-prone C57BL/6 genetic background, deficiency results hypergammaglobulinemia affects all immunoglobulin (Ig)G subclasses. Older (1 yr age)...
Experimental and preclinical evidence suggest that adoptive transfer of regulatory T (Treg) cells could be an appropriate therapeutic strategy to induce tolerance improve graft survival in transplanted patients. The University Kentucky Transplant Service Line is developing a novel phase I/II clinical trial with ex vivo expanded autologous Treg as cellular therapy renal transplant recipients who are using everolimus (EVR)-based immunosuppressive regimen.The aim this study was determine the...
HLA-specific killer cell inhibitory receptors (KIR) are thought to impede natural (NK) and T activation programs through recruitment of the SH2 domain-containing tyrosine phosphatases, SHP-1 SHP-2, their cytoplasmic tails (CYT). To identify other proteins that bind KIR CYT, we used recently described yeast two-bait interaction trap a modified version this system, both which permit phosphorylation bait proteins. Using these systems, show once phosphorylated by src-family kinase LCK,...
Mutations in PTEN ‐induced kinase 1 ( PINK 1), a serine/threonine linked to familial early‐onset Parkinsonism, compromise mitochondrial integrity and metabolism impair AKT signaling. As the activation of naïve T cell requires an ‐dependent reorganization cell's metabolic machinery, we sought determine if PINK1 ‐deficient cells lack ability undergo differentiation. We show that CD 4 + from knockout mice fail properly phosphorylate upon activation, resulting reduced expression IL ‐2 receptor...
Abstract Background & Aims The purpose of this study was to evaluate predictors outcomes in combined liver–kidney transplants for polycystic liver and kidney disease. Methods We queried the United Network Organ Sharing dataset performed from 1988 2013. Results Out 107 patients who had disease, 84 were women (78.5%) with a mean age 54.9 ±7.2 years. Kaplan–Meier analysis demonstrated that undergoing transplantation disease better survival than transplant alone those other indications. This...
We previously reported the isolation of a cDNA encoding T cell-specific adapter protein (TSAd). Its amino acid sequence contains an SH2 domain, tyrosines in binding motifs, and proline-rich regions. In this report we show that expression TSAd is induced normal peripheral blood cells stimulated with anti-CD3 mAbs or plus anti-CD28 mAbs. Overexpression Jurkat interfered TCR-mediated signaling by down-modulating anti-CD3/PMA-induced IL-2 promoter activity Ca2+ mobilization. The TCR-induced...
T cell–specific adapter protein (TSAd) is a SRC-homology-2 (SH2) domain–containing intracellular signaling molecule that required for cell antigen receptor (TCR)–induced cytokine synthesis in cells. How TSAd functions TCR signal transduction not clear. Previous work has suggested nuclear role this adapter. However, other evidence suggests also the cytoplasm. Using cells from TSAd-deficient mice, we now show major of cytoplasm activation LCK tyrosine kinase at outset transduction....
The development and maintenance of immunosuppressive CD4+ regulatory T cells (Tregs) contribute to the peripheral tolerance needed remain in immunologic homeostasis with vast amount self commensal antigens on human body. Perturbations balance between Tregs inflammatory conventional can result immunopathology or cancer. Although therapeutic injection has been shown be efficacious murine models colitis1 , type I diabetes2 rheumatoid arthritis graft versus host disease,4 several fundamental...
Abstract We provide evidence that platelet factor 4 (PF4), but not the related chemokine neutrophil-activating polypeptide-2, induced highly purified human natural killer (NK) cells to produce interleukin (IL)-8 in a time- and dosage-dependent manner. This ability was retained even while PF4 bound heparin. increased steady state level of IL-8 mRNA, likely implying transcriptional effect PF4. Stimulation NK through Fc receptor for immunoglobulin G-IIIA foud synergistically increase on...
T cell-specific adapter (TSAd) protein is an Src homology 2 (SH2) domain-containing molecule implicated in cell receptor for antigen (TCR)-mediated interleukin (IL-2) secretion cells. Here, we demonstrate that a substantial fraction of TSAd found the nucleus. Nuclear import active process depends on SH2 domain recognition phosphotyrosine-containing ligand. Importantly, show can act as potent transcriptional activator Furthermore, appears to be essential this transcription-activating function...
Regulatory T cell (Treg) therapy is considered an alternative approach to induce tolerance in transplantation. If successful, this may have implications on immunosuppression minimization/withdrawal reduce drug-induced toxicity patients. The aim of study was assess the efficacy mTORC1/C2 inhibitor, AZD8055, manufacturing clinically competent Treg cells and compare effects with those induced by rapamycin (RAPA), another mTOR inhibitor commonly used expansion protocols.Primary human were...