A5071545468- Immune Cell Function and Interaction
- Immunodeficiency and Autoimmune Disorders
- Cell death mechanisms and regulation
- T-cell and B-cell Immunology
- NF-κB Signaling Pathways
- Immunotherapy and Immune Responses
- interferon and immune responses
- Immune Response and Inflammation
- Chronic Lymphocytic Leukemia Research
- Metabolism and Genetic Disorders
- Lymphoma Diagnosis and Treatment
- Corneal surgery and disorders
- Phagocytosis and Immune Regulation
- Autophagy in Disease and Therapy
- Liver Disease Diagnosis and Treatment
- Cytomegalovirus and herpesvirus research
- Blood disorders and treatments
- Diabetes and associated disorders
- Viral-associated cancers and disorders
- RNA regulation and disease
- Gastrointestinal disorders and treatments
- Pediatric Hepatobiliary Diseases and Treatments
- Cytokine Signaling Pathways and Interactions
- Galectins and Cancer Biology
- HIV Research and Treatment
National Institute of Allergy and Infectious Diseases
2016-2025
National Institutes of Health
2016-2025
University of Pennsylvania
2010-2024
Vanderbilt University
2022
ID Genomics (United States)
2021
Rockefeller University
1998-2020
Cell Biologics (United States)
2020
Genomics (United Kingdom)
2016-2020
GTx (United States)
2014
Office of Extramural Research
2009-2014
Caspases play a central role in apoptosis, well-studied pathway of programmed cell death. Other programs death potentially involving necrosis and autophagy may exist, but their relation to apoptosis mechanisms regulation remains unclear. We define new molecular which activation the receptor-interacting protein (a serine-threonine kinase) Jun amino-terminal kinase induced with morphology autophagy. Autophagic required genes ATG7 beclin 1 was by caspase-8 inhibition. Clinical therapies caspase...
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory receptor found on immune cells. The consequences of mutations in CTLA4 humans are unknown. We identified germline heterozygous subjects with severe dysregulation from four unrelated families. Whereas Ctla4 mice have no obvious phenotype, human haploinsufficiency caused FoxP3(+) regulatory (Treg) cells, hyperactivation effector and lymphocytic infiltration target organs. Patients also exhibited progressive loss circulating B...
Autophagy plays a central role in regulating important cellular functions such as cell survival during starvation and control of infectious pathogens. Recently, it has been shown that autophagy can induce cells to die; however, the mechanism autophagic death program is unclear. We now show caspase inhibition leading by means involves reactive oxygen species (ROS) accumulation, membrane lipid oxidation, loss plasma integrity. Inhibition chemical compounds or knocking down expression key...
Heterozygous mutations encoding abnormal forms of the death receptor Fas dominantly interfere with Fas-induced lymphocyte apoptosis in human autoimmune lymphoproliferative syndrome. This effect, rather than depending on ligand-induced oligomerization, was found to stem from ligand- independent interaction wild-type and mutant receptors through a specific region extracellular domain. Preassociated complexes were living cells by means fluorescence resonance energy transfer between variants...
Individual protein-binding sites within the mouse immunoglobulin heavy chain and kappa light gene enhancers were altered, making it possible to examine functional role of during transcription. The E motifs, which bind factors that are present in many if not all cells, mostly behave as transcriptional activating sites. only known enhancer site binds a lymphocyte-specific factor, "octamer" site, plays critical transcription but truncated form enhancer. In full enhancer, no one is crucial...
Trafficking from bedside to bench Typically in translational research, a discovery cell or molecular biology is later exploited improve patient care. Occasionally, information flows the opposite direction. Lo et al. found that patients with an autoimmune disorder caused by deficiency of protein called LRBA responded dramatically drug abatacept (see Perspective Sansom). Abatacept contains segment potent inhibitory immune receptor, CTLA4. Experiments prompted this observation revealed...
Encounters with antigen can stimulate T cells to become activated and proliferate, nonresponsive antigen, or die. cell death was shown be a physiological response interleukin-2-stimulated cycling receptor reengagement at high doses. This feedback regulatory mechanism attenuates the immune by deleting portion of newly dividing, antigen-reactive cells. deleted autoreactive abrogated clinical pathological signs autoimmune encephalomyelitis in mice after repetitive administration myelin basic protein.
Members of the tumor necrosis factor (TNF) receptor (TNFR) superfamily are potent regulators apoptosis, a process that is important for maintenance immune homeostasis. Recent evidence suggests TNFR-1 and Fas TRAIL receptors can also trigger an alternative form cell death morphologically distinct from apoptosis. Because molecular components including serine/threonine protein kinase receptor-interacting (RIP) required, we have referred to this as "programmed necrosis." We show TNFR-2 signaling...
To identify novel antiapoptotic proteins encoded by DNA viruses, we searched viral genomes for that might interfere with Fas and TNFR1 apoptotic signaling pathways. We report here equine herpesvirus type 2 E8 protein molluscum contagiosum virus MC159 both show sequence similarity to the death effector domains (DEDs) of Fas/TNFR1 components FADD caspase-8. Yeast two-hybrid analysis revealed interacted caspase-8 prodomain whereas FADD. Furthermore, expression either or protected cells from...