A5011164353- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- Single-cell and spatial transcriptomics
- Immunodeficiency and Autoimmune Disorders
- Immune cells in cancer
- Viral Infections and Vectors
- Reproductive System and Pregnancy
- Immune Response and Inflammation
- Chronic Lymphocytic Leukemia Research
- Autoimmune and Inflammatory Disorders Research
- HIV-related health complications and treatments
- Viral-associated cancers and disorders
- Blood disorders and treatments
- Mosquito-borne diseases and control
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
Stanford University
2013-2017
Stanford Medicine
2016
National Institute of Allergy and Infectious Diseases
2014
National Institutes of Health
2012-2014
Laboratory of Molecular Genetics
2014
Both genetics and environment contribute to human NK cell diversity.
Human natural killer cell diversity is a metric of immune function associated with less effective antiviral response.
DOCK8 mutations result in an inherited combined immunodeficiency characterized by increased susceptibility to skin and other infections. We show that when DOCK8-deficient T NK cells migrate through confined spaces, they develop cell shape nuclear deformation abnormalities do not impair chemotaxis but contribute a distinct form of catastrophic death we term cytothripsis. Such defects arise during lymphocyte migration collagen-dense tissues DOCK8, CDC42 p21-activated kinase (PAK), is...
NK cells are responsible for recognizing and killing transformed, stressed, infected cells. They recognize a set of non-Ag-specific features termed "altered self" through combinatorial signals from activating inhibitory receptors. These NKRs also expressed on CD4(+) CD8(+) T cells, B monocytes, although comprehensive inventory NKR expression patterns across leukocyte lineages has never been performed. Using mass cytometry, we found that distinguish cell in human peripheral blood. In...
Epstein-Barr virus (EBV) is a human γ-herpesvirus that establishes latency and lifelong infection in host B cells while achieving balance with the immune response. When system perturbed through immunosuppression or immunodeficiency, however, these latently infected can give rise to aggressive cell lymphomas. Natural killer (NK) are regarded as critical early response viral infection, but their role controlling expansion of not understood. Here, we report NK from healthy donors display...
Background Natural killer (NK) cells have antiviral and antitumor activity that could be harnessed for the treatment of infections malignancies. To maintain cell viability enhance effects, NK are frequently treated with cytokines. Here they performed an extensive assessment effects cytokines on phenotype function human cells. Methods They used cytometry by time‐of‐flight (CyTOF) to evaluate repertoire changes after stimulation interleukin (IL)‐2, IL‐15 or a combination IL‐12/IL‐15/IL‐18....
West Nile virus (WNV) typically leads to asymptomatic infection but can cause severe neuroinvasive disease or death, particularly in the elderly. Innate NK cells play a critical role antiviral defenses, yet their human WNV is poorly defined. Here we demonstrate that mount robust, polyfunctional response characterized by cytolytic activity, cytokine and chemokine secretion. This associated with downregulation of activating cell receptors upregulation ligands for NKG2D. The did not differ...
Infection is a leading cause of death worldwide in babies under 1 month age. Better vaccines and therapeutics are desperately needed for this vulnerable population.Because newborns rely heavily on the innate immune system, we evaluated cell phenotype function some earliest cellular responders during infection, natural killer (NK) cells. We used mass cytometry to provide comprehensive comparison NK cells from umbilical cord blood adult peripheral blood.In unsupervised analyses, including...
ABSTRACT Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this are poorly understood, particularly for individuals effectively treated antiretroviral medications. We hypothesized that viral characteristics such as sequence diversity may play a role in HIV-associated activation. therefore sequenced proviral DNA isolated from...
EBV infection elicits a strong host immune response that is considered to be essential for control of the virus and preventing EBV-associated lymphomas in transplant recipients. The T cell following has been extensively characterized. Like cells, natural killer (NK) cells are lymphocytes capable responding viral by secretion cytokines including IFN-γ direct killing target via release cytotoxic granules. While NK have implicated EBV, evidence lacking, particularly regarding EBV+ B lymphomas....
Abstract NK cells respond to infected and transformed using germline-encoded receptors (NKRs). Collectively, these NKRs combine form distinct repertoires that tune the cell response. To provide a framework for understanding how perturbations in expression of influence disease pathogenesis, we defined phenotypic heterogeneity 22 healthy individuals (ages 21-62; M=10, F=12), including 5 sets monozygotic twins. Using mass cytometry, surface 38 markers specific lineage identify B cells, T...
Abstract Like their T and B lymphocyte counterparts, natural killer (NK) cells exist in small specialized subpopulations. However, while cell repertoire diversity is generated primarily through DNA rearrangement to produce a single antigen-specific receptor, the of NK determined by expression spectrum activating inhibitory receptors. To evaluate human on single-cell basis, we simultaneously measured more than 25 receptors peripheral blood 22 healthy individuals via mass cytometry. We used...