A5059681234- Cell death mechanisms and regulation
- Genomics and Chromatin Dynamics
- RNA Interference and Gene Delivery
- NF-κB Signaling Pathways
- interferon and immune responses
- Ubiquitin and proteasome pathways
- Malaria Research and Control
- Virus-based gene therapy research
- Cytokine Signaling Pathways and Interactions
- HIV Research and Treatment
- PARP inhibition in cancer therapy
- Cancer-related gene regulation
- Pregnancy and preeclampsia studies
- Cancer-related Molecular Pathways
- Protein Kinase Regulation and GTPase Signaling
- Epigenetics and DNA Methylation
- Global Maternal and Child Health
- Mitochondrial Function and Pathology
- Molecular Biology Techniques and Applications
- Phagocytosis and Immune Regulation
- Axon Guidance and Neuronal Signaling
- Melanoma and MAPK Pathways
- Angiogenesis and VEGF in Cancer
- Sirtuins and Resveratrol in Medicine
- Folate and B Vitamins Research
University of Michigan
1997-2022
Howard Hughes Medical Institute
2008-2010
Human Genome Sciences (United States)
1997
École Polytechnique Fédérale de Lausanne
1985
Expansion of a polyglutamine sequence in the N terminus huntingtin is gain-of-function event that causes Huntington's disease. This mutation affects primarily medium-size spiny neurons striatum. Huntingtin expressed many neuronal and non-neuronal cell types, implying more general function for wild-type protein. Here we report acts by protecting CNS cells from variety apoptotic stimuli, including serum withdrawal, death receptors, pro-apoptotic Bcl-2 homologs. protection may take place at...
The pivotal discovery that the death proteases caspase 8 (FLICE) and 10 (Mch4/FLICE2) are recruited to CD-95 tumor necrosis factor receptor-1 signaling complexes suggested a mechanism used by these cytotoxic receptors initiate apoptosis. In this report, we describe cloning characterization of I-FLICE, novel inhibitor receptor-1- CD-95-induced overall architecture I-FLICE is strikingly similar FLICE Mch4/FLICE2. However, lacks both catalytic active site residues form substrate binding pocket,...
Molluscum contagiosum virus proteins MC159 and MC160 the equine herpesvirus 2 protein E8 share substantial homology to death effector domain present in adaptor molecule Fas-associated (FADD) initiating protease FADD-like interleukin-1β-converting enzyme (FLICE) (caspase-8). FADD FLICE participate generating signal from both tumor necrosis factor receptor-1 (TNFR-1) CD-95 receptor. The flow of signals TNFR-1 occurs through receptor-associated (TRADD) FLICE, whereas for receptor directly...
Tumor nectosis factor (TNF) receptors are key players in inflammation and immune regulation. A new member of this family, termed death receptor‐6 (DR6), has been identified. Like other receptors, DR6 is a type I transmembrane receptor, possesses four extracellular cysteine‐rich motifs cytoplasmic domain. expressed most human tissues abundant transcript was detected heart, brain, placenta, pancreas, thymus, lymph node several non‐lymphoid cancer cell lines. interacts with TRADD, which...
The pivotal discovery that Fas-associated death domain protein (FADD) interleukin-1β-converting enzyme (FLICE)/MACH was recruited to the CD95 signaling complex by virtue of its ability bind adapter molecule FADD established this protease has a role in initiating pathway (Boldin, M. P., Goncharov, T. M., Goltsev, Y. V., and Wallach, D. (1996) Cell 85, 803-815; Muzio, Chinnaiyan, A. Kischkel, K. C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, Bretz, J. D., Zhang, Gentz, R., Mann, Krammer,...
A20, a novel zinc finger protein, is an inhibitor of tumor necrosis factor-induced apoptosis. The mechanism by which A20 exerts its protective effect currently unknown. Several isoforms the 14-3-3 proteins were found to interact with in yeast two-hybrid screen. bound several vitro. Moreover, transfected was preferentially bind endogenous η14-3-3 isoform, whereas β/ζ co-immunoprecipitated much less efficiently, and ϵ14-3-3 had intermediate affinity. Importantly, c-Raf, previously described...
Polycomb group proteins are transcriptional repressors recruited to many developmental control genes. The specificity of polycomb protein targeting is incompletely understood. Subunits repressive complexes (PRC) encoded by multigene families in vertebrates. Five chromodomain-containing CBX family thought mediate chromatin association PRC1 complexes. We visualized the recruitment using bimolecular fluorescence complementation (BiFC) analysis, wherein fragments fluorescent fused members and...
Polycomb group (PcG) transcription regulatory proteins maintain cell identity by sustained repression of numerous genes. The differentiation embryonic stem (ES) cells induces a genome-wide shift in PcG target gene expression. We investigated the effects and protein interactions on CBX family localization dynamics using fluorescence imaging. In mouse ES cells, different exhibited distinct distributions mobilities. Most were enriched foci known as bodies. Focus formation did not affect...
The p75 neurotrophin receptor (p75<sup>NTR</sup>) belongs to the tumor necrosis factor receptor/nerve growth superfamily. In some cells derived from neuronal tissues it causes cell death through a poorly characterized pathway. We developed system using conditionally immortalized striatal neurons, in which expression of p75<sup>NTR</sup> is inducibly controlled by ecdysone receptor. these induces apoptosis its domain nerve factor-independent manner. Caspases 9, 6, and 3 are activated...
Glucose uptake and metabolism inhibit hypoxia-induced apoptosis in a variety of cell types, but the underlying molecular mechanisms remain poorly understood. In present study, we explore hypoxia-mediated death pathways Jurkat cells presence absence extracellular glucose. glucose, hypoxia caused cytochrome c release, caspase 3 poly(ADP-ribose)polymerase cleavage, DNA fragmentation; this apoptotic response was blocked by 9 inhibitor z-LEHD-FMK. The glucose during prevented release activation...
Apoptosis is mediated by a highly regulated signal transduction cascade that eventually leads to precisely directed cell death. The death‐inducing signaling complex (DISC), composed of Fas, FADD, and caspase‐8, an apical mediates receptor‐induced apoptosis. We have docked the experimentally determined structures Fas FADD death domains into model partial DISC complex. arrangement was using interaction modes two heterodimer crystal date, Pelle/Tube Apaf‐1/procaspase‐9. proposed reveals both...
Neurotrophin receptor alike death domain protein (NRADD) is a death-receptor-like with unique ectodomain and an intracellular homologous to p75(NTR). Expression of NRADD results in apoptosis, but only certain cell types. This paper characterizes the expression proteolytic processing mature 55 kDa glycoprotein. N-terminally truncated processed by gamma-secretase activity that requires presenilins has same susceptibility inhibitors as secretion amyloid beta (A beta). The endogenous shed...
The developmentally regulated sea urchin early histone gene repeat (SUEHGR) from Strongylocentrotus purpuratus was isolated as chromatin by nucleoprotein hybridization.This technique is a novel method to isolate specific sequences chromatin.Because the purification scheme based only on sequence and independent of other physical properties such protein composition transcriptional activity, we were able same in different functional states.Gene size fragments solubilized restriction...
Cell fusion is known to underlie key developmental processes in humans and postulated contribute tissue maintenance even carcinogenesis. The mechanistic details of cell fusion, especially between different types, have been difficult characterize because the dynamic nature process inadequate means track products over time. Here we introduce an inducible system for detecting tracking live vitro potentially vivo. This based on BiFC (bimolecular fluorescence complementation) analysis. In this...
Abstract Background Malaria in Mali remains a primary cause of morbidity and mortality, with women at high risk during pregnancy for placental malaria (PM). Risk PM its association birth outcomes was evaluated rural to urban longitudinal cohort on the Bandiagara Escarpment District Bamako. Methods Placental samples (N = 317) were collected from 249 mothers who participants prospective study directed by BIS years 2011 2019. A pathologist research assistant histology blinded fashion assess...
Collection, preservation, and shipment of histological specimens in low-resource settings is challenging. We present a novel method that achieved excellent preservation placental from rural Mali by using formalin fixation, ethanol dehydration, long-term storage solar-powered freezer. Sample success was 92%, permitting evaluation current past malaria infection, anemia, maturity, inflammation. Using RNAscope® hybridization we were able to visualize cell-specific gene expression patterns the...