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🚨CellChorus PUBLICATION ALERT - Nature Cancer publication identifies a clinically effective subset of CAR T cells by profiling with TIMING™ 📊 THE RESULTS: New research published in Nature Cancer by co-authors from the University of Houston, Kite Pharma (Gilead Sciences), the MD Anderson Cancer Center, Texas Children's Hospital / Baylor College of Medicine, and CellChorus applied TIMING analysis to identify a subpopulation of T cells (CD8-fit cells) that are migratory and capable of serial killing. The percent of CD8-fit cells within infusion products was correlated with complete clinical responses. ⚡THE SIGNIFICANCE: Chimeric antigen receptor (CAR) T cells can be a life-saving treatment for patients with cancer and other disorders. Despite this promise, not all patients respond to therapy and some experience severe side effects. It is therefore essential to identify recipients who are likely to benefit. 📄 THE APPROACH: Scientists conducted multifaceted single-cell analysis of CAR T cells from axi-cel infusion products of patients with diffuse large B-cell lymphoma, including dynamic single-cell analysis with the TIMING platform. 🔬 THE PLATFORM: TIMING applies AI+ML to quantify how individual immune cells move, interact, kill, survive, and secrete biomolecules in their interactions with target cells at single-cell resolution. Migration and serial killing are two readouts unique to dynamic single-cell analysis. 📄 EXAMPLE USE CASES: Data and insights from the TIMING platform enable the field to develop, manufacture and deliver novel therapies faster, at less expense, and with higher rates of success to benefit patients in oncology, autoimmune disorders, infectious diseases, and a wide range of other diseases and disorders. See examples of how leaders in the field have applied TIMING data in a variety of applications: cellchorus.com/resources 🧪 GET ACCESS: CellChorus offers early access to leading biopharmaceutical companies and academic/medical research institutions for research, development, translational medicine, and process development. Contact the CellChorus team: TIMING@cellchorus.com 📰 READ THE ANNOUNCEMENT: https://lnkd.in/gQexPnVf ✍️ AUTHORS: Ali Rezvan, Gabrielle Romain, Mohsen Fathi, Darren Heeke, Melisa A. Martínez Paniagua, PhD, Xingyue (Amy) An, Irfan bandey, Melisa Montalvo, Jay R Adolacion, Arash Saeedi, Fatemeh Sadeghi, Ph.D., Kristen Fousek, Ph.D., Nahum Puebla, Laurence Cooper, Chantale Bernatchez, Harjeet Singh, Nabil Ahmed, Mike Mattie, Adrian Bot, M.D., Ph.D., Sattva Neelapu, Navin Varadarajan #cellTherapy #CART #CARTcellTherapy #oncology #cancer #immunotherapy #immunoOncology #AI #ML #deepLearning #singleCell #liveCellImaging Rebecca Berdeaux, Daniel Meyer Springer Nature Group UH Cullen College of Engineering, UH Technology Bridge

🚨 #publicationalert: Necroptosis induced by ruthenium (II) complexes as mitochondrial disruptors The study, led by researchers of Faculty of Pharmacy and co-authored by myself (iBB-Institute for Bioengineering and Biosciences/Instituto Superior Técnico), looks into how ruthenium (II) complexes cause necroptosis, a type of programmed cell death, via mitochondrial disruption. Necroptosis differs from apoptosis in that it involves cellular swelling, membrane rupture, and inflammation. #Highlights: 💡 Ruthenium (II) complexes disrupt the mitochondrial membrane potential, leading to mitochondrial dysfunction. 💡 This disruption triggers the necroptotic pathway, specifically through the involvement of receptor-interacting protein kinases (RIPK1 and RIPK3) and mixed lineage kinase domain-like protein (MLKL). 💡 The activation of these proteins leads to the formation of necrosomes, which are critical for the execution of necroptosis. 💡 The mitochondrial disruption caused by ruthenium (II) complexes results in the release of reactive oxygen species (ROS) and other pro-death signals. 💡 These signals amplify the necroptotic response, leading to extensive cell death in the targeted cancer cells. See more details: https://lnkd.in/dcHtbsHT

In vitro data demonstrate that miconazole may exert anti-melanoma activity, and that this effect is counteracted by carnitine. The study also demonstrates strong mitochondrial involvement in the anti-melanoma activity of miconazole. Se the manuscript at https://lnkd.in/dw44RZkq

Dive deeper into the complexities of biology with multiplex immunohistochemistry (IHC). This powerful technique enables researchers to analyze multiple protein markers within a single tissue sample, providing critical insights into spatial interactions between distinct cell types. By studying these interactions in their natural environment, multiplex IHC enhances biomarker discovery and unveils pathways with therapeutic potential. 🖼️ Featured Antibody: The anti-cortactin antibody ABIN2854674 [https://lnkd.in/eDYVikZ6] shows exceptional labeling in the granular and external plexiform layers of the mouse olfactory bulb, with additional staining in synapses and neuronal processes. 👉 Learn more about our validated multiplex IHC antibodies.

Crossing the blood-brain barrier is one of the Holy Grails in the CNS space — an incredibly difficult challenge for delivering larger molecules to the brain. Could Wang et al. (2024) have finally cracked the code with their BBB-crossing conjugate (BCC) system? The team led by Yizhou Dong (Professor of Immunology and Immunotherapy at Icahn Mount Sinai) utilizes a biological process called γ-secretase-mediated transcytosis to deliver large therapeutic molecules, such as oligonucleotides or proteins, directly into the brain via an intravenous injection. They have tested this platform in mouse models and isolated human brain tissue. You can find the full article here: https://lnkd.in/dr64tDWE Source: Wang, C., Wang, S., Xue, Y. et al. Intravenous administration of blood–brain barrier-crossing conjugates facilitate biomacromolecule transport into central nervous system. Nat Biotechnol (2024). https://lnkd.in/euJkT-kn

**Finally CRISPR goes into clinical trial** A research team led by Jennifer Doudna (received the Nobel Prize in Chemistry in 2020, shared with Emmanuelle Charpentier for inventing CRISPR technology) has initiated a publicly funded clinical trial to treat sickle cell disease (SCD) using a novel CRISPR-based gene-editing approach. Unlike commercial strategies, this trial uses a non-viral single-stranded oligonucleotide donor to directly correct the SCD mutation via homology-directed repair. The project will emphasize accessibility and safety, with initial recruitment focusing on adults, followed by adolescents. The study aims to achieve curative outcomes with reduced risks compared to bone marrow transplants. Results from this pioneering trial could influence future SCD treatments significantly. #CRISPR #GeneEditing #Genomics

𝗧𝗮𝗿𝗴𝗲𝘁𝗶𝗻𝗴 𝗽𝘂𝗿𝗶𝗻𝗲 𝗻𝘂𝗰𝗹𝗲𝗼𝘁𝗶𝗱𝗲 𝘀𝘆𝗻𝘁𝗵𝗲𝘀𝗶𝘀 𝗮𝘀 𝗮 𝗺𝗲𝘁𝗮𝗯𝗼𝗹𝗶𝗰 𝘃𝘂𝗹𝗻𝗲𝗿𝗮𝗯𝗶𝗹𝗶𝘁𝘆 𝗶𝗻 𝗯𝗿𝗮𝗶𝗻 𝗺𝗲𝘁𝗮𝘀𝘁𝗮𝘀𝗲𝘀 Metabolic aberrations are not only a means to generate energy for tumors. They also contribute to the production of building blocks including nucleotides. As this brilliant experimental paper shows, targeting GTP synthesis could help treat brain metastases. This could provide a huge benefit for advanced cancers that currently have a very poor prognosis. https://lnkd.in/d4C_5WD9 Full publication: Kieliszek, A. M., Mobilio, D., Bassey-Archibong, B. I., Johnson, J. W., Piotrowski, M. L., de Araujo, E. D., Sedighi, A., Aghaei, N., Escudero, L., Ang, P., Gwynne, W. D., Zhang, C., Quaile, A., McKenna, D., Subapanditha, M., Tokar, T., Vaseem Shaikh, M., Zhai, K., Chafe, S. C., Gunning, P. T., … Singh, S. K. (2024). De novo GTP synthesis is a metabolic vulnerability for the interception of brain metastases. Cell reports. Medicine, 101755. Advance online publication. https://lnkd.in/d6Jd3n6S. Freely available under a Creative Commons license: https://lnkd.in/d72Y4gs6 #science #metabolism #pharmacology #precisionmedicine #oncology

We are beyond excited to share our latest work on the role of peroxiredoxin 6 (PRDX6) in #ferroptosis out today in Molecular Cell and spearheaded by two exceptional postdocs in our lab Helmholtz Munich: Eikan Mishima and Junya Ito. This study proposes PRDX6 as a novel ferroptosis regulator by acting as an intracellular selenium transport protein. Its role is crucial for effectively utilizing selenium, a vital component for synthesizing selenoproteins, including GPX4, thereby regulating the propensity to undergo #ferroptosis. Our findings furthermore suggest that PRDX6 could be a promising therapeutic target for cancer treatment via ferroptosis modulation. It may also offer valuable clues to better understand the underlying mechanisms driving #neurodegenerative disease. My heartfelt appreciation goes out to all collaborators and funding agencies, including Deutsche Forschungsgemeinschaft (DFG) - German Research Foundation, and the European Research Council (ERC), having made this achievement possible! The full article can be found here: https://lnkd.in/dWQhhtNW

#Review Recent Advances in Fluorescent Methods for Polyamine Detection and the Polyamine Suppressing Strategy in Tumor Treatment by Lingyun Wang and Derong Cao https://lnkd.in/g3WQ53h9   #MDPI #Fluorescent #Biochemical #Tumor #biosensors #sensors #openaccess   #Abstract The biogenic aliphatic polyamines (spermine, spermidine, and putrescine) are responsible for numerous cell functions, including cell proliferation, the stabilization of nucleic acid conformations, cell division, homeostasis, gene expression, and protein synthesis in living organisms. The change of polyamine concentrations in the urine or blood is usually related to the presence of malignant tumors and is regarded as a biomarker for the early diagnosis of cancer. Therefore, the detection of polyamine levels in physiological fluids can provide valuable information in terms of cancer diagnosis and in monitoring therapeutic effects. In this review, we summarize the recent advances in fluorescent methods for polyamine detection (supramolecular fluorescent sensing systems, fluorescent probes based on the chromophore reaction, fluorescent small molecules, and fluorescent nanoparticles). In addition, tumor polyamine-suppressing strategies (such as polyamine conjugate, polyamine analogs, combinations that target multiple components, spermine-responsive supramolecular chemotherapy, a combination of polyamine consumption and photodynamic therapy, etc.) are highlighted. We hope that this review promotes the development of more efficient polyamine detection methods and provides a comprehensive understanding of polyamine-based tumor suppressor strategies.

Our new paper is finally out! In this study, we discovered that the human tumor suppressor protein Pdcd4 binds to the mRNA entry channel in the 40S small ribosomal subunit. Pdcd4 blocks the eIF4F-independent role of eIF4A during mRNA recruitment and scanning. This paper is particularly special to me as it is my first as a corresponding author and likely my last as a first author. Exciting times lie ahead as I continue my research with the talented students and postdocs in my lab at the University of Michigan Medical School #mRNA #cryoEM #ribosome https://lnkd.in/gYcTceWv