A5067972666- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- Immunodeficiency and Autoimmune Disorders
- Asthma and respiratory diseases
- Blood disorders and treatments
- Erythrocyte Function and Pathophysiology
- Lysosomal Storage Disorders Research
- IL-33, ST2, and ILC Pathways
- Prion Diseases and Protein Misfolding
- Phagocytosis and Immune Regulation
- Cell death mechanisms and regulation
- CAR-T cell therapy research
- Nuclear Structure and Function
- Immunotherapy and Immune Responses
- Genetic Neurodegenerative Diseases
National Institute of Allergy and Infectious Diseases
2020-2024
National Institutes of Health
2020-2024
Saha Institute of Nuclear Physics
2017-2020
University of Virginia
2019
RIKEN
2017
Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated that renders immunological studies challenging. They have CD4+ αβ T lymphocytopenia concomitant expansion CD4−CD8− double-negative (DN) Vδ2− γδ lymphocytes, both displaying unique CD38+CD45RA+T-bet+EOMES− phenotype. Itk-deficient mice recapitulated an the DN lymphocyte...
Patients with activated phosphatidylinositol 3-kinase delta (PI3Kδ) syndrome (APDS) present sinopulmonary infections, lymphadenopathy, and cytomegalvirus (CMV) and/or Epstein-Barr virus (EBV) viremia, yet why patients fail to clear certain chronic viral infections remains incompletely understood. Using patient samples a mouse model (Pik3cdE1020K/+ mice), we demonstrate that, upon activation, Pik3cdE1020K/+ CD8+ T cells exhibit exaggerated features of effector populations both in vitro after...
ESCRT proteins are implicated in myriad cellular processes, including endosome formation, fusion of autophagosomes/amphisomes with lysosomes, and apoptosis. The role played by these either facilitating or protecting against apoptosis is unclear. In this study, while trying to understand how deficiency Mahogunin RING finger 1 (MGRN1) affects cell viability, we uncovered a novel for its interactor, the ESCRT-I protein TSG101: it directly participates mitigating ER stress-mediated association...
Presence of cytosolic protein aggregates and membrane damage are two common attributes neurodegenerative diseases. These delay degradation non-translocated precursors leading to their persistence accumulation in the cytosol. Here, we find that cells with intracellular (of prion or huntingtin) destabilize endoplasmic reticulum (ER) morphology dynamics when load is high. This affects trafficking proteins out from ER, relative distribution rough smooth ER three-way junctions essential for...
Abstract Allergic diseases are a major global health issue, causing significant morbidity and mortality. Interleukin-9 (IL-9) producing T helper 9 (Th9) cells promote allergic inflammation, yet Th9 effector functions incompletely understood because the heterogeneity instability of makes them challenging to study. Although significance mechanisms unknown, cell receptor (TCR) activation is hypothesized play key role. Conversely this paradigm, we found that resting did not require TCR...
Abstract IL-2 inducible T cell kinase (Itk) is a critical component of receptor (TCR) signaling required for activation PLCg and downstream transcription factors, that regulate expression effector molecules. Loss Itk impairs T-cell by modulating the strength TCR signal. −/−mice have defects in development with decreased proliferation impaired differentiation to multiple CD4 helper lineages. Most severe are seen Th9 cells, which produce cytokine, IL-9. Under conditions, −/−cells initially...