A5089184804- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Chemokine receptors and signaling
- Diffusion and Search Dynamics
- Acute Lymphoblastic Leukemia research
- Early Childhood Education and Development
- Cytokine Signaling Pathways and Interactions
- Asthma and respiratory diseases
- Monoclonal and Polyclonal Antibodies Research
- Parental Involvement in Education
- Artificial Immune Systems Applications
- Galectins and Cancer Biology
- Indigenous and Place-Based Education
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Cellular Mechanics and Interactions
- Pulmonary Hypertension Research and Treatments
- SARS-CoV-2 and COVID-19 Research
- Aging and Gerontology Research
- IL-33, ST2, and ILC Pathways
- interferon and immune responses
- CAR-T cell therapy research
- Autophagy in Disease and Therapy
University of New Mexico
2015-2024
Mathematica Policy Research
2022
New Mexico Cancer Center
2015-2019
UNM Comprehensive Cancer Center
2019
University of Chicago
2001-2013
University of Bristol
2011
Pulmonary and Critical Care Associates
2008
We have shown previously that Wiskott-Aldrich syndrome protein (WASP) activation at the site of T cell-APC interaction is a two-step process, with recruitment dependent on proline-rich domain and binding Cdc42-GTP to GTPase domain. Here, we show WASP occurs through C-terminal Src homology 3 Nck. In contrast, requires Vav-1. Vav-1-deficient cells, proceeds normally, but localized Cdc42 disrupted. The are coordinated by tyrosine-phosphorylated 2 domain-containing leukocyte 76 kDa, which...
Mast cells (MCs) produce soluble mediators such as histamine and prostaglandins that are known to influence dendritic cell (DC) function by stimulating maturation antigen processing. Whether direct cell–cell interactions important in modulating MC/DC is unclear. In this paper, we show contact between MCs DCs occurs plays an role the immune response. Activation of through FcεRI cross-linking triggers formation stable with immature reminiscent immunological synapse. Direct cellular...
Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of response, required for clearance pathogenic infection. cell activation requires that encounter antigen-bearing dendritic within lymph nodes, thus, patterns nodes may be a crucial determinant how quickly response can initiated. Previous work suggests motion node is similar to Brownian random walk, however, no detailed analysis has definitively shown whether movement...
Inflammation is a prominent pathological feature in pulmonary arterial hypertension, as demonstrated by vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution adaptive immune system not well characterized hypertension caused chronic hypoxia. CD4 + cells are required for initiating maintaining inflammation, suggesting that these could play an important role pathogenesis hypoxic hypertension. Our objective was to test hypothesis specifically...
T cells interacting with APCs undergo rearrangement of surface receptors and cytoskeletal elements to face the zone contact APC. This polarization process is thought affect cell signaling by organizing a specialized domain on direct effector function toward appropriate We have investigated contribution TCR, CD28, LFA-1 assaying response an Ag-specific Th1 clone panel transfected expressing MHC class II alone or in combination ICAM-1 B7-1. show that talin, actin-binding protein, occurs...
Wiskott-Aldrich syndrome protein (WASP)-deficient T cells exhibit defects in IL-2 production that are widely believed to stem from primary actin remodeling and immune synapse formation. Surprisingly, however, we find WASP-deficient responding Ag-specific APCs polymerize organize talin PKC theta normally, forming an is stable for at least 3 h. At low doses of peptide, show less efficient polarization. Thus, although WASP may facilitate formation peptide concentrations, not required this...
CD43 is a glycosylated surface protein abundantly expressed on lymphocytes. Its role in immune responses has been difficult to clearly establish, with evidence supporting both costimulatory and inhibitory functions. In addition, its contribution disease pathogenesis remains elusive. Using well-characterized murine model of elastase-induced abdominal aortic aneurysm (AAA) that recapitulates many key features the human disease, we established presence T cells required for AAA formation....
Effector T cell migration through tissues can enable control of infection or mediate inflammatory damage. Nevertheless, the molecular mechanisms that regulate effector cells within interstitial space inflamed lungs are incompletely understood. Here, we show in a mouse model acute lung injury with two-photon imaging intact tissue. Computational analysis indicates migrate an intermittent mode, switching between confined and almost straight migration, guided by lung-associated vasculature....
Abstract Tauopathies, including frontotemporal dementia (FTD) and Alzheimer’s disease (AD) are progressive neurodegenerative diseases clinically characterized by cognitive decline could be caused the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles (NFTs) inside neurons. There is currently no FDA-approved treatment that cures, slows or prevents tauopathies. Current immunotherapy strategies targeting pTau have generated encouraging data but may pose...
Although inhibitory Fcγ receptors have been demonstrated to promote mucosal tolerance, the role of activating in modulating T helper type (Th)2-dependent inflammatory responses characteristic asthma and allergies remains unclear. Here, we demonstrate that signaling via conjunction with Toll-like receptor 4 stimulation modulated cytokine production from bone marrow–derived dendritic cells (DCs) augmented their ability Th2 responses. Ligation low affinity FcγRIII was specifically required for...
T cells play a vital role in eliminating pathogenic infections. To activate, na¨ıve search 5 lymph nodes (LNs) for dendritic (DCs). Positioning and movement of LNs is 6 influenced by chemokines including CCL21 as well multiple cell types structures the 7 LNs. Some previous studies have suggested that positioning facilitates DC colocalization 8 leading to T:DC interaction. Despite influence chemical signals, cells, can 9 on positioning, relatively few used quantitative measures directly 10...
Genomes of viruses are constrained by the virions nanoscale, and viral nucleotide sequences without function a luxury. Yet double-stranded DNA genome human adenovirus (HAdV) contains large regions known purpose. Using TRANSFAC ChIP-Seq analysis, we identified binding OCT4 (octomer-binding transcription factor 4) to noncoding region HAdV-D37 DNA. Manipulation expression impacted E3 gene gp19k protein expression, altering subsequent MHC Class I expression. These effects were specific 5ʹ...
Abstract Despite the defined function of β-catenin pathway in thymocytes, its functional role peripheral T cells is poorly understood. We report that a mouse model, protein constitutively degraded cells. Introduction stabilized into primary inhibited proliferation and cytokine secretion after TCR stimulation blunted effector cell differentiation. Functional biochemical studies revealed selectively linker for activation phosphorylation on tyrosine 136, which was associated with defective...
A key question in SARS-CoV-2 infection is why viral loads and patient outcomes vary dramatically across individuals. Because spatial-temporal dynamics of spread immune response are challenging to study vivo, we developed Spatial Immune Model Coronavirus (SIMCoV), a scalable computational model that simulates hundreds millions lung cells, including respiratory epithelial cells T cells. SIMCoV replicates growth observed patients shows how spatially dispersed infections can lead increased...
Electronic cigarette (Ecig) use has become more common, gaining increasing acceptance as a safer alternative to tobacco smoking. However, the 2019 outbreak of Ecig and Vaping-Associated Lung Injury (EVALI) alerted community potential for incorporation deleterious ingredients such vitamin E acetate into products without adequate safety testing. Understanding induced molecular changes in lung systemically can provide path assessment protect consumers from unsafe formulations. While been...
Activating mutations in cytokine receptors and transcriptional regulators govern aberrant signal transduction T-cell lineage acute lymphoblastic leukemia (T-ALL). However, the roles played by suppressors of signaling remain incompletely understood. We examined regulatory suppressor 5 (SOCS5) T-ALL cellular networks progression. found that SOCS5 was differentially expressed primary its expression levels were lowered HOXA-deregulated harboring KMT2A gene rearrangements. Here, we report is...
Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory and has been shown to augment proliferation survival of activated cells. However, the ICOS costimulation development maintenance remains controversial. Herein, we describe significant defect number effector (EM) phenotype ICOS−/− ICOSL−/− mice that becomes progressively more dramatic age. This decrease was...
Cell polarization is a key feature of cell motility, driving migration to tissues. CD43 an abundantly expressed molecule on the T-cell surface that shows distinct localization migrating uropod and distal pole complex (DPC) opposite immunological synapse via association with ezrin-radixin-moesin (ERM) family actin regulatory proteins. regulates multiple functions, including activation, proliferation, apoptosis, migration. We recently demonstrated trafficking through phosphorylation site at...
SUMMARY Detection of targets distributed randomly in space is a task common to both robotic and biological systems. Lévy search has previously been used characterize T cell the immune system. We use robot swarm evaluate effectiveness strategy map relationship between parameters target configurations. show that fractal dimension which optimizes efficiency depends strongly on distribution but only weakly number agents involved search. can therefore be tuned configuration while also being...
The migratory capacity of adaptive CD8αβ T cells dictates their ability to locate target and exert cytotoxicity, which is the basis immune surveillance for containment microbes disease. small intestine (SI) largest mucosal surface a primary site pathogen entrance. Using two-photon laser scanning microscopy, we found that motility antigen (Ag)-specific in SI dynamic varies with environmental milieu. Pathogen-specific cell movement differed throughout infection, becoming locally confined at...