Start Codon’s Post

Rachel Watkins is Director of Experimental Biology at CoSyne Therapeutics, a company working on creating a platform for drug discovery in under-served brain diseases, based on high-quality scientific data integrated with AI and machine learning. We all know the saying ‘garbage in, garbage out’ so CoSyne have concentrated on generating the highest quality, clinically relevant data for their platform. Focusing initially on astroglial diseases, including aggressive brain cancers, CoSyne aim to develop a model that can aid drug discovery for brain diseases and beyond. Working from a biobank of patient-derived tumour cell lines, cells are grown in 3D culture to mimic tumour conditions as closely as possible e.g. hypoxia gradient. These cells are then characterised through whole-genome sequencing, single-cell transcriptomics and CRISPRi screens and these data used to power AI generated cellular simulations in order to identify biomarker / target pairings. To verify their platform’s efficiency CoSyne have identified biomarker/target pairings already established in the literature as well as many novel targets. This work has shown that the platform is working well and CoSyne are currently looking at re-purposing phase I safe but de-prioritised therapeutics towards new indications to accelerate the path of new treatments for patients in need. Rachel will be speaking at Drug Discovery 2024 on Thursday 3 October in the track ‘Target discovery and disease modelling’. Register now to catch her talk at Drug Discovery 2024: https://lnkd.in/ePmtmfN9 #braincancer #CRISPR #braindisease #singlecellsequencing #singlecell #therapeutics #cancer #tumor #braintumor #genomics #wholegenomesequencing #transcriptomics

Weekly Digest of Breakthroughs and Setbacks in Clinical Research! ⚡🔬 Clinical trials: 🧪 ❌ BioVie Inc. | primary efficacy endpoint missed statistical significance in phase 3 trial of oral, small molecule NE3107 in patients with mild to moderate Alzheimer’s disease ✅ EyePoint Pharmaceuticals| 80% reduction in treatment burden with drug containing tyrosine kinase inhibitor in patients with wet age-related macular degeneration in a phase 2 trial ✅ BiomX Inc | BX004 showed clinically meaningful improvement in pulmonary function in patients with cystic fibrosis in a phase 1b/2a Trial Science: 🔬 Scientists at 🇺🇸 St. Jude Children's Research Hospital discovered that adding a modular chimeric cytokine receptor to CAR T cells increased efficacy in solid tumor models Researchers at 🇺🇸 UC Davis Comprehensive Cancer Center have shown that inhibiting the protein galectin 1 using gene therapy can shrink hepatocellular carcinoma in mice Researchers at 🇪🇸 Vall d'Hebron Institute of Oncology (VHIO) have found that adding immune checkpoint inhibitor atezolizumab to standard of care with bevacizumab and chemotherapy improves progression-free survival and overall survival in patients with metastatic cervical cancer, in a phase 3 trial Subscribe to our newsletter for more partnering updates! 🔗 https://lnkd.in/dsgz62YY #clinicaltrials #drugdevelopment #clinicalresearch #clinicaltrial #drugdesign #science #drugdiscovery #research

CAR-T is a game-changer for blood cancer. However, there is a lot about them we still don’t know. Omics data could be that missing piece of the puzzle.      In this review, the authors review how multidimensional omics data can improve CAR T therapy.   So what is Omics?   Omics aims to collectively identify, characterise, and quantify all biological molecules that are involved with: The function of the cell The dynamics of the cell, tissue, or organism.   Examples of omics include: Genomics Transcriptomics Proteomics   But how can they help?   The authors go through various examples including:   1. Target discovery for CAR-T therapies This involves using transcriptomics and proteomics to identify differences in protein expression between malignant and non-malignant cells, to identify targets. As well as the development of combinational CAR constructs which require the expression of several ligands to induce CAR-T cell killing.     2. Enhancing CAR-T cell efficacy and persistence – Here, transcriptomics profile CAR-T cells before the infusion to relieve the expression of IL-6 STAT3 pathways which results in early memory phenotype led to improved CAR-T response.   3. Tumour characteristics How do tumours become resistant? One case demonstrated how combined genomics and transcriptomics revealed a CD19-CAR was infused into a single leukaemic B cell resulting in expression and blocking the binding of CD19-CAR T cells due to the cis binding.   4. Minimising CAR-T cell-related toxicities Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common clinical side effect of CAR-T cell treatment. However, some important discoveries include the increased risk of ICANS with CD19 CAR-T cells expressing high levels of IL-1β. Kudos to the authors Jingwen Yang, Yamei Chen, Ying Jing, Michael R. Green and Leng Han excellent work! https://lnkd.in/gJHkJ_Vv #celltherapyjournalclub #celltherapy #biotechnology #innovation

It gives me immense pleasure to share the recent copyright granted on "Protocol for Compilation of Differentially Regulated Molecules for Esophageal Squamous Cell Cancer"  It describes a protocol outline with a vital methodology for identifying significant molecular alterations, especially differentially regulated genes (DEGs) or differentially expressed proteins (DEMs) in cancer, which paves the way for the development of innovative diagnostic and therapeutic strategies for esophageal squamous cell carcinoma (ESCC). By employing advanced genomic and proteomic techniques, this protocol enables researchers to uncover epigenetic alterations, and abnormal gene or protein expression, which are pivotal in ESCC pathogenesis. The detailed molecular profiling steps facilitated by this protocol not only enhance our understanding of the disease mechanisms but also identify potential biomarkers for early detection and disease monitoring. The data generated through this process would help in providing a set of DEGs/DEMs that could be useful not only for the discrimination between ESCC vs. normal tissues but also for the development of targeted therapy is for ESCC. Therefore, this protocol represents a cornerstone step in ongoing efforts from our group to combat ESCC by identifying DEGs/DEMs to translate research from bench to bedside, ultimately aiming to enhance diagnostic/prognostic accuracy and therapeutic efficacy for ESCC patients. Consequently, this approach holds promise for improving patient outcomes through more precise and personalized treatment regimens. Furthermore, this protocol can be extrapolated to other diseases and malignancies as well. I am thankful to my colleague, Dr. Manoj K Kashyap, who was the guiding figure to make this idea come into reality. We hope that this protocol makes a significant contribution to the scientific community. #copyright #cancercells #ESSC #DEGs #DEMs #targetteddrugdelivery #medicine #therapeutics #diagnostic #translationalresearch #STEM #amityuniversity

Researchers from TGen, part of City of Hope, and from UC San Diego have identified a set of genes that helps predict whether a patient’s glioblastoma might respond to some promising drugs called neddylation (NAE) inhibitors. The findings published in the journal Neuro-Oncology Advances Oxford Academic Oxford University Press will help Michael Berens, Ph.D., professor and head of the Glioma Research Lab, and his colleagues as they design clinical trials aimed at personalizing glioblastoma #treatment. New treatments for #glioblastoma, the most common and most deadly primary brain tumor, are desperately needed. These tumors are characterized by a large and complex variety of molecular aberrations, such that a treatment that works against one patient’s tumor may not work in another patient. As a result, there have been more than 300 clinical trials for glioblastoma therapies that did not advance a drug to FDA approval, said Berens. “The pharmacopeia for treating brain tumors is abysmally slim,” he added, “and new drug approvals for glioblastoma are tragically rare events.” NAE inhibitors, which affect protein turnover in cells, have shown impressive results against #myeloma, and appear promising in #glioblastoma models. But researchers need to know more about which glioblastomas are vulnerable to NAE inhibitor treatment, and why others may be resistant. The #scientists studied genetic alterations and biological processes operating in human glioma cell lines and patient-derived xenografts, finding differences in signaling by the well-known tumor suppressor protein PTEN and in pathways for DNA replication and repair. Based on these differences, the researchers developed an NAE Inhibition Response Gene Set—a set that could be used to predict which glioblastoma would be vulnerable to NAE inhibitors. And once a drug is FDA-approved, “then we can use those drugs in combination with other drugs like an immune checkpoint inhibitor or a DNA damage repair inhibitor, and that’s where the big win is going to be for brain tumor patients,” Berens said. Read the full story at: https://bit.ly/3XYcbly #biomedical #research #clinicaltrials #innovation #collaboration #cancer

I am excited to share that our research on “Network Dynamics and Therapeutic Aspects of mRNA and Protein Markers within the Recurrence Sites of Pancreatic Cancer,” guided by Dr. Animesh Acharjee (Assistant Professor, University of Birmingham) has been published in the multidisciplinary (Q1) journal, #Heliyon  Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a high mortality rate and challenging diagnosis. Our study aimed to identify genes, proteins, and clinical parameters to uncover stable molecular associations across multiple #PDAC recurrences that could be used as therapeutic tools in the future. We employed #statistical methods such as Spearman partial correlation analysis, univariate analysis, dimension reduction (PLS), machine learning techniques, and network construction to achieve these findings. I am immensely grateful to all my mentors and team members for this research project. As I look forward to new research opportunities, I am eager to explore further collaborations in this impactful field. I appreciate your support and look forward to connecting with others who are passionate about advancing cancer research. I would highly appreciate your referrals and recommendations. #CancerResearch #PancreaticCancer #Machinelearning #Proteomics #Multiomics #Cancertherapeutics #Metabolomics #Bioinformatics #ScientificJournals #ResearchOpportunities #NetworkDynamics #OpenToWork #CareerOpportunities #HelpingHand #Researchscientists

#AMCDiscoveries Solitary fibrous tumor/Hemangiopericytoma (SFT/HPC) is a rare subtype of soft tissue sarcoma harboring NAB2-STAT6 gene fusions. Mechanistic studies and therapeutic development on SFT/HPC are impeded by scarcity and lack of system models. Researchers from National Cancer Centre Singapore (NCCS) and Duke-NUS Medical School conducted a study, to establish and characterise a novel SFT/HPC patient-derived cell line (PDC), SFT-S1, and screen for potential drug candidates that could be repurposed for the treatment of SFT/HPC. In their study, they established a novel PDC model of SFT/HPC with comprehensive characterization of its genomic, epigenomic and transcriptomic landscape, which can facilitate future preclinical studies of SFT/HPC, such as in vitro drug screening and in vivo drug testing. “Through this work we have made a small step in the understanding of Rare Cancers, an important disease area not to be ignored”, said Asst Prof Chan Yong Sheng Jason, Consultant, Division of Medical Oncology, NCCS. Read more in Human Cell, SpringerLink: https://bit.ly/3RYNQYp AMC researchers involved: Jing Yi Lee, Abner Lim, Zexi Guo, Li Zhimei (NCCS), Jessica Sook Ting Kok, Elizabeth Chun Yong Lee, Lim Boon Yee (Bonnie), Bavani Kannan, Jui Wan Loh, Cedric Ng, Kah Suan Lim, Bin Tean Teh, Tun Kiat Ko, Jason Yongsheng Chan, MBBS-PhD #AMRInews #research #Singapore #biomedical #epigenomics #rarecancers #nextgenerationsequencing #NCCS #DukeNUS #SingHealth #AMC Visit SingHealth Duke-NUS AM Research Institute (AMRI) at bit.ly/aboutAMRI

🧬 The Latest Product Launches in the Omics sector 🧬 🧬 Bio-Rad Laboratories launches the ddPlex ESR1 Mutation Detection Kit, a highly sensitive digital PCR assay for translational research, therapy selection, and disease monitoring. Detects seven ESR1 mutations with exceptional sensitivity and same-day results. 🧬 QIAGEN introduces the QiAcuity dPCR PanCancer Kits for EGFR and BRAF mutations and the QiaSeq Targeted RNA-seq Panel for T-cell receptors, enabling precise cancer monitoring and immune repertoire characterization. 🧬 Element Biosciences unveils Aviti24, an instrument for next-gen sequencing and multiomic profiling, offering comprehensive analysis of DNA, RNA, proteins, and cell structure in under 24 hours. 🧬 Takara Bio USA, Inc. presents the Shasta Single-Cell System, an automated platform for biomarker discovery in oncology research, enabling whole-genome DNA amplification and total RNA-seq. 🧬 Bruker Canopy Biosciences CellScape Imaging Chamber enhances spatial multiplexing, allowing simultaneous staining of large tissue sections for increased throughput and flexibility. 🧬 Mission Bio: Sample Multiplexing for Tapestri: Mission Bio introduces sample multiplexing for its Tapestri single-cell DNA and protein analysis platform, streamlining workflows and accelerating genomic research. 🧬 Nonacus launches Galeas Tumor, a comprehensive genomic profiling test using next-gen sequencing, offering insights into cancer genetics and personalized medicine. 🧬 LGC Clinical Diagnostics releases Seraseq cfDNA NIPT Reference Materials for accurate noninvasive prenatal testing, supporting fetal trisomy 21 and microdeletion 22q11 syndromes. #genomics #research #biotech #innovation #pcr #ngs #cancer #oncology #biomarkers #precisionmedicine #digitalpcr #sequencing #singlecell #diagnostics #rnaseq #lifesciences #healthcare #precisionhealth

Happy to announce that our paper is now published in Scientific Reports https://lnkd.in/dzpRywmn Formalin-fixed paraffin-embedded (FFPE) tissue is a valuable resource for cancer research, but extracted nucleic acids are often degraded and prone to artefacts. In this study we: (i) evaluate the degree of concordance between FFPE and Fresh-Frozen material in matched breast cancer tissue samples for certain RNA and DNA applications in published literature (ii) demonstrate the feasibility of the simultaneous DNA and RNA extraction method on FFPE material after comparing three silica-based nucleic acid extraction methods (iii) explore its performance using surgical tumour-rich FFPE material from patients enrolled in the Scandinavian Breast Group (SBG) 2004-1 multicenter randomized phase II clinical trial on the following platforms and addressing the need to exclude variants below 5% variant allele frequency to overcome FFPE-induced artefacts. a) targeted DNA NGS platform (using hybrid-capture 370-gene GMCK panel) for DNA b) hybridisation-based nCounter system (using BC360 panel) for RNA #Foukakis_Group #FFPE #Breast_Cancer #SweBCG #Karolinska_Institutet

As drug development technology advances, the potential for predictive biomarkers is truly exciting! Recently, a group at the NIH developed a computational pipeline to analyze single cell expression data from patient tumors, with the goal of predicting which therapies would benefit each patient the most. Although this was focused on therapies targeting tumor-intrinsic biology, the day is coming when something like this will take shape for immuno-therapy. The tumor immune microenvironment is incredibly complex, and with predictive biomarkers, we can better match treatments to individual patients. What advancements in predictive biomarkers are getting you excited these days? #drugdevelopment #predictivebiomarkers #personalizedmedicine #healthtech