A5019910792- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
- Parkinson's Disease Mechanisms and Treatments
- Melanoma and MAPK Pathways
- Nuclear Receptors and Signaling
- Cellular transport and secretion
- Cell death mechanisms and regulation
- Cytokine Signaling Pathways and Interactions
- Endoplasmic Reticulum Stress and Disease
- Neurological disorders and treatments
- bioluminescence and chemiluminescence research
- Cancer Mechanisms and Therapy
- COVID-19 Clinical Research Studies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Plant-based Medicinal Research
- RNA regulation and disease
- Immune Cell Function and Interaction
- Signaling Pathways in Disease
- Immunotherapy and Immune Responses
- Bacterial biofilms and quorum sensing
- Retinal Development and Disorders
- Genetics and Neurodevelopmental Disorders
- Microtubule and mitosis dynamics
- Vibrio bacteria research studies
University of Wisconsin–Madison
2024
Immunome (United States)
2021-2023
University of California, Los Angeles
1996-1998
University of California, San Francisco
1997-1998
Neurons undergoing apoptosis can be rescued by trophic factors that simultaneously increase the activity of extracellular signal-regulated kinase (ERK) and decrease c-Jun N-terminal (JNK) p38. We identified a molecule, CEP-1347 (KT7515), rescues motoneurons investigated its effect on ERK1 JNK1 activity. Cultured rat embryonic motoneurons, in absence factor, began to die 24–48 hr after plating. During first 24 was unchanged, whereas increased fourfold. completely for at least 72 with an EC 50...
CEP-1347 (KT7515) promotes neuronal survival at dosages that inhibit activation of the c-Jun amino-terminal kinases (JNKs) in primary embryonic cultures and differentiated PC12 cells after trophic withdrawal mice treated with 1-methyl-4-phenyl tetrahydropyridine. In an effort to identify molecular target(s) JNK cascade, JNK1 known upstream regulators were co-expressed Cos-7 determine whether could modulate activation. blocked induced by members mixed lineage kinase (MLK) family (MLK3, MLK2,...
The c-Jun N-terminal kinase signaling cascade appears to play a role in some cases of cell death, including neuronal apoptosis. CEP-1347 (KT7515), an indolocarbazole the K252a family, blocks this stress and promotes survival. Here, we used probe whether death pathways activated by distinct insults also possess elements common. Cultured rat sympathetic neurons neuronally differentiated PC12 cells were induced die withdrawal nerve growth factor, exposure ultraviolet irradiation, or subjection...
Cell survival, death, and stress signals are transduced from the cell surface to cytoplasm nucleus via a cascade of phosphorylation events involving mitogen-activated protein kinase (MAPK) family. We compared distribution p42 (p42MAPK) its activator MAPK or ERK (MEK1; involved in transduction growth differentiation signals), with c-Jun N-terminal (JNK1) MEK4 (involved death signals) adult rat central nervous system. All four kinases were present cytoplasm, dendrites, axons neurons. The...
Immune checkpoint inhibitors that overcome T cell suppressive mechanisms in tumors have revolutionized the treatment of cancer but are only efficacious a small subset patients. Targeting acting on innate immune cells could significantly improve incidence clinical response by facilitating multi-lineage against tumor involving both adaptive and systems. Here, we show intra-tumoral interleukin (IL)-38 expression is feature large frequency head neck, lung cervical squamous cancers correlates...
In vitro studies indicate that p42/p44MAPK phosphorylate both nuclear and cytoplasmic proteins. However, the functional targets of activation in vivo remain unclear. To address this question, we localized activated hippocampus cortex determined their signaling effects after electroconvulsive shock treatment (ECT) rats. Phosphorylated content increased cytoplasm hippocampal neurons response to ECT. Consistent with localization, inhibition ECT-induced by extracellular signal-regulated kinase...
Molecular cloning has identified two vesicular monoamine transporters (VMATs), one expressed in non-neural cells of the periphery (VMAT1) and other by multiple cell populations brain (VMAT2). Functional analysis previously shown that VMAT2 a higher affinity than VMAT1 for neurotransmitters as well inhibitor tetrabenazine. The chimeric also major regions required high interactions with these ligands. We have now used site-directed mutagenesis to identify individual residues responsible...
Overexpression of gp120, the major coat protein HIV-1 virus, in central glial cells, or treatment neurons with gp120 culture, produces apoptotic neuronal death. Here we demonstrate that CEP-1347 (KT7515), an inhibitor mixed lineage kinase 3 (MLK3), upstream activator JNK, inhibits gp120IIIB-induced apoptosis hippocampal neurons. Furthermore, expression wild type MLK3 pyramidal enhanced neurotoxicity, whereas a dominant negative protected from toxic effects glycoprotein. These results...
The two closely related vesicular monoamine transporters (VMATs) 1 and 2 differ substantially in ligand recognition. neuronal VMAT2 exhibits a higher affinity for substrates particular histamine as well greater sensitivity to the inhibitor tetrabenazine than nonneuronal VMAT1. analysis of chimeric transport proteins has previously shown that major domains, one spanning transmembrane domains (TMDs) 5–8 (TMD5–8) other, TMDs 9–12 (TMD9–12), are required high interactions characteristic VMAT2....
ABSTRACT Type VII protein secretion systems play an important role in the survival and virulence of pathogens competition among some microbes. Potential polymorphic toxin substrates type system (T7SS) Bacillus subtilis are for context biofilm communities. Within a biofilm, there is significant physiological heterogeneity as cells within population take on differential cell fates. Which express deploy various T7SS still unknown. To identify which at least one substrates, we investigated yfj...
Abstract Using an unbiased interrogation of the memory B cell repertoire convalescent COVID-19 patients, we identified human antibodies that demonstrated robust antiviral activity in vitro and efficacy vivo against all tested SARS-CoV-2 variants. Here, describe pre-clinical characterization antibody cocktail, IMM-BCP-01, consists three unique, patient-derived recombinant neutralizing directed at non-overlapping surfaces on spike protein. Two antibodies, IMM20184 IMM20190 directly block...