Marianne Goodwin, PhD

I'm thrilled to FINALLY share our big newly published study in Communication Biology with Amy Vincent, Tracey Davey CSci MIScT FRMS, Ross Laws, Conor Newcastle University, Newcastle Research facilities, linked to my PhD research "Mapping mitochondrial morphology and function: COX-SBFSEM," is now published in Communications Biology. In this study, we introduce COX-SBFSEM, a novel imaging technique that combines cytochrome c oxidase (COX) cytochemistry with serial block-face scanning electron microscopy (SBFSEM). This method allows for high-resolution, three-dimensional mapping of mitochondrial morphology and function within muscle fiber. And COX-SBFSEM reveals how mitochondrial structure-function changes drive disease. In brief Our study shows : 1- Pioneering Quantitative Analysis: Our study is the first to assess mitochondrial morphology and COX function in skeletal muscle from patients with large-scale mtDNA deletions using 3D imaging (SBFSEM). 2- Three Mitochondrial Populations Identified: Normal, intermediate, and deficient mitochondria were observed, based on their COX activity. 3- Morphology Linked to Dysfunction: COX-deficient mitochondria exhibit simpler structures, highlighting a direct link between mitochondrial function and shape. 4- Intermediate Mitochondria's Role: Intermediate mitochondria may play a key role in the spatial spread of dysfunction across muscle fibres. 5-Groundbreaking Insights: our work provides unprecedented detail on how mitochondrial function and morphology are interconnected, previously impossible to measure in situ. You can read the full article here: https://lnkd.in/d3pMTNeQ #Mitochondria #mitochondrialdisease #EM #3DEM #SBFSEM #muscle #research

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New from the lab this week, Pd(COD)(DQ), trans-spanning ligands, and soluble formate are combined to give massively expanded scope in regioreversed additions to activated olefins. https://lnkd.in/gSAimVcj Tipping our Santa caps 🎅 to Wenji He, Evan Morgan, Sara Shanker, and the team.

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Pengfei Liu, PhD, FACMGG, is discussing everything RNA-seq in next week's journal club! Don't miss his live presentation delving into the specifics on this innovative rare disease diagnostic workflow. During Dr. Liu's presentation he'll tackle: 🧬How transcriptome RNA-seq using accessible tissues can fall short in characterizing genes involved in neurological disorders. 💡How cell transdifferentiation is streamlined into a diagnostic RNA-seq workflow. 🥼How to increase molecular diagnostic yield by activating neurological disease-associated genes and neuron-specific isoforms with induced neuron RNA-seq. Gain these insights on June 12 by registering today: https://lnkd.in/eeH-XUHJ #ASHG #HumanGenetics

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Partnership and collaboration were key in developing the nAbCyte™ CDx assay for determining patient eligibility in the BEQVEZ™ gene therapy program. Today, we’re proud to run sponsored testing programs in the U.S. and Canada, supporting providers as they use this breakthrough to identify patients who may benefit from this novel therapy. Learn more: https://lnkd.in/ev_C7spB #GeneTherapy #CDx

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Now published in Science Advances, a collaborative study with the University of Maryland IBBR Institute for Bioscience and Biotechnology Research Mariuzza Lab on structural characterization of a human T cell receptor and its dual recognition of NRAS Q61K and Q61R cancer neoantigens. AlphaFold2 (via TCRmodel2) and AlphaFold3 modeling of the complexes largely recapitulated the X-ray structures, underscoring the potential of deep learning methods in this context, while additional modeling highlighted some possible limitations and room for improvement. https://lnkd.in/eJhJvCVw

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In the U.S., common cancers all demonstrate significant racial disparities in outcomes. Genomic testing, which analyzes tumor cells or circulating tumor DNA to guide cancer treatment, is increasingly used in precision oncology, yet data on similar disparities in its use are limited. DPHS’ Clare Meernik, PhD, MPH, Devon Check, Hayden Bosworth, and Tomi Akinyemiju worked on a retrospective cohort study of cancer patients diagnosed at the Duke Cancer Institute to better determine what potential disparities exist: https://lnkd.in/exjRjyRu #populationhealth #cancer #cancercare #healthdisparities

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Two updates to announce today: 1- The House might be done with appropriations for the moment, but we aren't done talking about them. I've actually written a recap of everything that is included in the bills they've passed so far - including calculations of what fraction of the funding will do directly to the performance of research (R&D Estimates) and how the agencies fared in terms of total appropriations. https://lnkd.in/dyqTwpEF 2- The Senate is marking up their next suite of appropriations bills in committee as we speak, and I've updated the FY 2025 dashboard with the accounts I could find in the bill summaries that have been released so far. I'll update them again later when the bill text and reports are released. https://lnkd.in/eNKVqyfh

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Grateful for the opportunity to share our recent work on multiple myeloma at ASH 2024. Our study highlights the potential of 5-hydroxymethylcytosine (5hmC) in cell-free DNA as a non-invasive tool for predicting response to front-line therapy in multiple myeloma patients. #ASH24

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NIH researchers unveil a new mechanism by which mutant RAS proteins drive cancer, paving the way for innovative combination therapies targeting pancreatic, lung, and other RAS-driven cancers. #NIHDiscoveries #CancerResearch #ResearchandDevelopment(R&D) #NIH #RASMutations #MarketAccessToday #MarketAccess

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I would highly recommend taking a look at our publication. https://lnkd.in/dBQwFqbU TITLE CAR NK cell therapy in hematologic malignancies and solid tumors; obstacles and strategies to overcome the challenges ABSTRACT Adoptive cell treatment (ACT) utilizing chimeric antigen receptors (CAR) diverts the specificity of safe cells against a target-specific antigen and portrays exceptional potential for cancer treatment. While CAR T cell treatment has risen as a breakthrough with unprecedented results within the therapeutic procedures of human malignancies, different deficiencies including challenging and costly generation processes, strict patient qualification criteria, and undesirable toxicity have ruined its application. Unlike T cells, the application of natural killer (NK) cells has attracted consideration as a reasonable alternative owing to the major histocompatibility complex (MHC)-independency, shorter life expectancy, the potential to create an off-the-shelf immune product, and potent antitumor properties. In this article, we provide an updated review of the differences between CAR T and CAR NK cells, current enhancements in CAR NK design, the available sources for collecting NK cells, and strategies for the transduction step of the CARs to NK cells. Furthermore, we focus on the published and ongoing preclinical and clinical studies of CAR NK treatment strategies both in hematologic malignancies and solid tumors. We also discuss limitations and plausible solutions to improve the perseverance, function, safety, and efficacy of CAR NK cells with a special focus on solid tumors.

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🚨 New Manuscript Alert! 🚨 I’m thrilled to share our latest study, now available on bioRxiv: “Macropinocytosis controls metabolic stress-driven CAF subtype identity in pancreatic cancer”. Highlights from our findings: 🔬 Pancreatic ductal adenocarcinoma (PDAC) adapts to glutamine depletion by stimulating macropinocytosis, not only in tumor cells but also in cancer-associated fibroblasts (CAFs). 🌟 We uncover how macropinocytosis regulates CAF subtype identity under metabolic stress, revealing an intrinsic inflammatory CAF (iCAF) program driven by MEK/ERK signaling. 🧩 By targeting macropinocytosis, we can reorganize the tumor stroma and sensitize PDAC to immunotherapy and chemotherapy—a step toward more effective treatments for this aggressive cancer. Special recognition goes to the incredible first author, Yijuan Zhang, whose dedication and expertise drove this work forward. Yijuan is an amazing scientist, and her contributions to understanding the metabolic crosstalk in PDAC have been nothing short of inspiring! A huge thank you to the entire team for their hard work and collaboration on this impactful project. We’re excited to see how these findings will spark new therapeutic strategies for PDAC. Take a look at the manuscript here: https://lnkd.in/giq6X8sf #PancreaticCancer #CancerResearch #Macropinocytosis #TumorMicroenvironment #PDAC #Collaboration

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Incredible! SLAC National Accelerator Laboratory’s “electron camera” can reveal some of nature’s #ultrafast processes. Now, researchers across the lab have collaborated to achieve improvements to that tool to make its #molecular movies even sharper, keeping #SLAC at the forefront of pioneering tools for ultrafast #science. The Megaelectronvolt Ultrafast Electron Diffraction (MeV-UED) instrument at the Linac Coherent Light Source (LCLS) at SLAC is a kind of high-speed “electron camera” that allows researchers to watch the inner workings of a chemical reaction or a material as it changes and reacts to its environment. https://lnkd.in/gaEWfeZN

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Two important firsts in genome editing 1. Fetal non-human primate base editing delivers to multiple organs https://t.co/p7HAc0NvUQ 2. A.I.-generated gene editors success in human cells https://lnkd.in/gSKGGuTd

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Something to be concerned. Science must be based on ethics and honesty. These actions along with buying authorships are unacceptable behaviors that need to be eradicated. We probably should start on critically discussing how we value CVs for career development. https://lnkd.in/dR4Abh9i

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Could Digestive Enzymes Contribute to Aging? UCSD researchers have hypothesized a mechanism of aging called “autodigestion”- where digestive enzymes like trypsin, normally confined to the small intestine, leak into peripheral organs as we age. This leakage causes significant tissue damage, resulting in higher levels of collagen damage within organs linking this autodigestion to aging. Using Collagen Hybridizing Peptides (CHPs) to detect damaged collagen, the study revealed how this enzyme leakage accelerates aging and harms vital tissues. Here are their key findings:  Older rats showed higher collagen damage across multiple organs, including the liver, lungs, heart, brain, skin, and kidneys. This damage was closely linked to the presence of leaked digestive enzymes. When older rats were treated with a serine protease inhibitor for just two weeks, enzyme leakage and collagen damage were significantly reduced, offering a potential therapeutic approach. Implications: These findings imply that dietary habits, such as meal frequency and caloric intake, could influence the rate of enzymatic leakage and associated tissue damage, shedding a light on new avenues for therapeutic and lifestyle interventions to preserve tissue integrity and metabolic health. Learn more by reading our full blog and the paper itself here: https://lnkd.in/eHKegbDU

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If you're at #EADVCongress and want to learn about how state-of-the-art technologies such as genomics, single-cell RNAseq and spatial transcriptomics are shedding light on skin cancer pathogenesis, come join my presentation at 1640 today in the Actinic Keratosis updates session (room 7.1).

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May is #MentalHealthAwarenessMonth! Join the conversation by sharing how you prioritize moments of well-being. Whether it's a walk, a good book, a new tune or practicing mindfulness, let's show that mental health matters every day! - Keith, UW Postdoc Fellow #TakeTheMoment

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