A5036915290- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- CAR-T cell therapy research
- Pancreatic function and diabetes
- Diabetes Management and Research
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Ferroptosis and cancer prognosis
- Neonatal Respiratory Health Research
- Axon Guidance and Neuronal Signaling
- Congenital Diaphragmatic Hernia Studies
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Infant Nutrition and Health
- Macrophage Migration Inhibitory Factor
- PI3K/AKT/mTOR signaling in cancer
- Immune Response and Inflammation
- Ubiquitin and proteasome pathways
- Visual perception and processing mechanisms
- Angiogenesis and VEGF in Cancer
- Neuroblastoma Research and Treatments
- 14-3-3 protein interactions
University of Utah
2020-2024
Baylor College of Medicine
2015-2023
Texas Children's Hospital
2015-2023
City University of Seattle
2020
Texas Medical Center
2018
Diabetes Australia
2018
St. Jude Children's Research Hospital
2010-2017
Sidney Kimmel Comprehensive Cancer Center
2011
Johns Hopkins University
2011
Stanford University
2011
Inhibitory receptors on immune cells are pivotal regulators of escape in cancer. Among these inhibitory receptors, CTLA-4 (targeted clinically by ipilimumab) serves as a dominant off-switch while other such PD-1 and LAG-3 seem to serve more subtle rheostat functions. However, the extent synergy cooperative interactions between pathways cancer remain largely unexplored. Here, we reveal extensive coexpression tumor-infiltrating CD4(+) CD8(+) T three distinct transplantable tumors. Dual...
Metabolic pathways regulate T cell development and function, but many remain understudied. Recently, the mitochondrial pyruvate carrier (MPC) was identified as transporter that mediates entry into mitochondria, promoting oxidation. Here we find deleting Mpc1, an obligate MPC subunit, in hematopoietic system results a specific reduction peripheral αβ numbers. MPC1-deficient cells have defective thymic at β-selection, intermediate single positive (ISP)-to-double-positive (DP), selection steps....
Abstract Early growth response gene 1 (Egr1) codes for a transcriptional regulator that contains zinc-finger DNA binding domain. Egr1 expression is induced by variety of extracellular stimuli including TCR-ligand interactions. Its pattern in the thymus and dependence on ERK activation have led to speculation it has role T cell development, but exact nature this been undefined. To more clearly define thymocyte we analyzed thymocytes from Egr1-deficient mice. We find thymuses mice contain...
T cell receptor (TCR) affinity is a critical factor of Treg lineage commitment, but whether self-reactivity determining in peripheral function remains unknown. Here, we report that high degree crucial for tissue-specific autoimmunity. Based on expression CD5, identified subset self-reactive Tregs expressing elevated levels T-bet, GITR, CTLA-4, and ICOS, which imparted significant protection from autoimmune diabetes. We observed T-bet Tregs, necessary control Th1 autoimmunity, could be...
Abstract For the αβ or γδTCR chains to integrate extracellular stimuli into appropriate intracellular cellular response, they must use 10 ITAMs found within CD3 subunits (CD3γε, CD3δε, and ζζ) of TCR signaling complex. However, it remains unclear whether each specific ITAM sequence individual subunit (γεδζ) is required for thymocyte development any particular motif sufficient. In this article, we show that mice utilizing a single (γ, ε, δ, ζa, ζb, ζc) at locations exhibit substantial...
Abstract Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional cells. However, the extent to which affinity regulates function of Tregs is largely unknown. In this study, we used two-TCR model assess role in Treg during autoimmunity. We observed that high- low-affinity were recruited pancreas contributed protection from autoimmune diabetes. Interestingly, high-affinity preferentially upregulated TCR-dependent functional mediators...
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of infants that characterized by interrupted development. Postnatal sepsis causes BPD, yet the contributory mechanisms are unclear. To address this gap, studies have used lipopolysaccharide (LPS) during alveolar phase However, lungs who develop BPD still in saccular development, and effects LPS poorly characterized. We hypothesized exposure disrupts development promote inflammation prevent optimal repair. Wild-type C57BL6J mice were...
Abstract The TCR:CD3 complex transduces signals that are critical for optimal T cell development and adaptive immunity. In resting cells, the CD3ε cytoplasmic tail associates with plasma membrane via a proximal basic-rich stretch (BRS). this study, we show mice lacking functional CD3ε-BRS exhibited substantial reductions in thymic cellularity limited CD4–CD8– double-negative (DN) 3 to DN4 thymocyte transition, because of enhanced TCR signaling resulting increased death downregulation all...
Abstract The contribution of low‐affinity T cells to autoimmunity in the context polyclonal T‐cell responses is understudied due limitations their capture by tetrameric reagents and low level activation response antigenic stimulation. As a result, are often disregarded as nonantigen‐specific irrelevant immune response. Our study aimed assess how self‐antigen reactivity shapes lineage effector spontaneous tissue‐specific observed NOD mice. Using multicolor flow cytometry combination with...
Phosphorylation of MAP kinases is important for proper translation T cell antigen receptor (TCR) signals into thymocyte fates, but the role kinase phosphatase (MKP) activity in development has not been characterized. To explore MKP thymocytes, we constructed a double mutant MKP-3 (DM-MKP3) that acts as dominant-negative inhibitor ERK- and JNK-specific MKP. Thymocytes developing presence DM-MKP3 have enhanced frequencies both CD4 CD8 mature, single-positive cells no increase apoptosis....
Abstract Type 1 diabetes is a T cell–mediated autoimmune disease that characterized by Ag-specific targeting and destruction of insulin-producing β cells. Although multiple studies have the pathogenic potential cell–specific cells, we limited mechanistic insight into self-reactive cell development their escape from negative selection in thymus. In this study, demonstrate ectopic expression insulin epitope B:9–23 (InsB9–23) thymic APCs insufficient to induce deletion high- or low-affinity...
Foxp3+ regulatory T cells (Tregs) are capable suppressors of aberrant self-reactivity. However, TCR affinity and specificities that support Treg function, how these compare to autoimmune remain unresolved. In this study, we used antigen agnostic epitope-focused analyses repertoires effector spontaneously infiltrate pancreatic islets non-obese diabetic mice. We show cell-derived TCRs possess similar wide-ranging reactivity for self-antigen. Treg-derived varied in their capacity confer optimal...
Abstract Conventional immunosuppressive functions of CD4 + Foxp3 regulatory T cells (Tregs) in type 1 diabetes (T1D) pathogenesis have been well described, but whether Tregs additional non-immunological supporting tissue homeostasis pancreatic islets is unknown. Within the last decade novel repair ascribed to Tregs. One function production epidermal growth factor receptor (EGFR) ligand, amphiregulin, which promotes response inflammatory or mechanical injury. However, such pathways are...
Type 1 diabetes is an autoimmune-mediated disease that culminates in the targeted destruction of insulin-producing β-cells. CD4 responses NOD mice are dominated by insulin epitope B:9-23 (InsB
T cell receptor (TCR) signaling is essential in the development and differentiation of cells thymus periphery, respectively. The vast array TCRs proves studying a specific antigenic response difficult. Therefore, TCR transgenic mice were made to study positive negative selection as well peripheral activation, proliferation tolerance. However, relatively few have been generated any given antigen. Thus, studies involving varying affinities for same peptide lacking. generation new line can take...
A neural network for extraction of salient contours in visual images is presented. The reproduces some typical characteristics information processing the primary cortex. Cells cortex are grouped to represent 100/spl times/100 distinct hypercolumns; each hypercolumn consists 16 cells with different orientation preferences. Each cell receives input from lateral geniculate nucleus, arranged along preferred according a Gabor function. cortical also further feedforward inhibitory interneurons,...