Disruption of endoplasmic reticulum-mitochondria tethering proteins in... Neurobiology of Disease, 2020

Abstract Signaling between the endoplasmic reticulum (ER) and mitochondria regulates a number of key neuronal functions, many of which are perturbed in Alzheimer's disease. Moreover, damage to ER-mitochondria signaling is seen in cell and transgenic models of Alzheimer's disease. However, as yet there is little evidence that ER-mitochondria signaling is altered in human Alzheimer's disease brains. ER-mitochondria signaling is mediated by interactions between the integral ER protein VAPB and the outer mitochondrial membrane prot...



Activation of MC1R with BMS-470539 attenuates neuroinflammation via cA... Journal of Neuroinflammation, 2021

Abstract Microglia-mediated neuroinflammation plays a crucial role in the pathogenesis of hypoxic-ischemic (HI)-induced brain injury. Activation of melanocortin-1 receptor (MC1R) has been shown to exert anti-inflammatory and neuroprotective effects in several neurological diseases. In the present study, we have explored the role of MC1R activation on neuroinflammation and the potential underlying mechanisms after neonatal hypoxic-ischemic brain injury in rats. This study demonstrates that activation of MC1R with BMS-470539 attenuated neuro...



Human perinatal stem cell derived extracellular matrix enables rapid m... Nature, 2020

Abstract The immature phenotype of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is a major limitation to the use of these valuable cells for pre-clinical toxicity testing and for disease modeling. Here we tested the hypothesis that human perinatal stem cell derived extracellular matrix (ECM) promotes hiPSC-CM maturation to a greater extent than mouse cell derived ECM. We refer to the human ECM as Matrix Plus (Matrix Plus) and compare effects to commercially available mouse ECM (Matrigel). hiPSC-CMs cultured on Mat...



Dynamic spatiotemporal coordination of neural stemcell fate decisions... Cell Stem Cell, 2021

Abstract Neural stem cell (NSC) populations persist in the adult vertebrate brain over a lifetime, and their homeostasis is controlled at the population level through unknown mechanisms. Here, we combine dynamic imaging of entire NSC populations in their in vivo niche over several weeks with pharmacological manipulations, mathematical modeling, and spatial statistics and demonstrate that NSCs use spatiotemporally resolved local feedback signals to coordinate their decision to divide in adult zebrafish brains. These involve No...



A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-... bioRxiv, 2021

Abstract The host cell serine protease TMPRSS2is an attractive therapeutic target for COVID-19 drug discovery. This protease activates theSpike protein of Severe Acute Respiratory SyndromeCoronavirus 2 (SARS...



pHLIP peptide targets nanogold particles to tumors PNAS, 2013

Abstract Progress in nanomedicine depends on the development of nanomaterials and targeted delivery methods. In this work, we describe a method for the preferential targeting of gold nanoparticles to a tumor in a mouse model. The method is based on the use of the pH Low Insertion Peptide (pHLIP), which targets various imaging agents to acidic tumors. We compare tumor targeting by nonfunctionalized nanogold particles with nanogold–pHLIP conjugates, where nanogold is covalently attached to the N terminus of pHLIP. Our most important fi...



LincRNA-immunity landscape analysis identifies EPIC1 as a regulator of... Science Advances, 2021

The ability of tumor cells to evade immune detection plays a critical role in tumor development. Although mechanisms of immune evasion have been characterized, understanding of how tumor cells avoid detection by the immune system and acquire resistance to immunotherapy remains incomplete. Utilizing Bio X Cell’s anti-mouse PD-1 (clone J43) antibody, researchers discovered that expression of the intergenic long noncoding RNA (lincRNA) EPIC1 helps cancer...



D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Prote... Cell Reports, 2021

In Brief: SARS-CoV-2 spike undergoes large conformational changes during cell fusion. Gobeil et al. identify a subdomain anchor that limits large motions in the receptor binding subunit of the pre-fusion spike from propagating to its fusion subunit. They demonstrate that theD614G mutation increases the rate off urin cleavage, which may impact infectivity. Jackson ImmunoResearch´s Peroxidase-AffiniPure Goat Anti-Human IgG, Fc gamma Fragment Specific JIM-109-035-098 was used...



ISG15-dependent activation of the sensor MDA5 is antagonized by the SA... Nature Microbiology, 2021

Abstract Activation of the RIG-I-like receptors, retinoic-acid inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), establishes an antiviral state by upregulating interferon (IFN)-stimulated genes (ISGs). Among these is ISG15, the mechanistic roles of which in innate immunity still remain enigmatic. In the present study, we report that ISG15 conjugation is essential for antiviral IFN responses mediated by the viral RNA sensor MDA5. ISGylation of the caspase activation and recruitment domains of MDA5 promotes i...



A vaccine targeting mutant IDH1 in newly diagnosed glioma Nature, 2021

The availability of anti-IDH1 R132H antibody clone H09 (DNA-DIA-H09, Dianova, Germany) developed by the German Cancer Research Center (DKFZ) in Heidelberg has triggered fundamental advances for the 2016 WHO classification of CNS tumors (https://pubmed.ncbi.nlm.nih.gov/27157931/ ). IDH1 R132H IHC has been introduced as a backbone for differential diagnosis of glioma. Now, early in 2021 in the Journal Natur...