Understanding Biological Processes

Is Cancer a Mitochondrial Disease? A Paradigm Shift in Oncology 🧬🔬 For decades, cancer has been viewed as a genetic disease, driven by mutations in nuclear DNA that lead to uncontrolled cell division. However, emerging research challenges this narrative, suggesting that mitochondria—the cell’s powerhouses—might play a pivotal role in cancer initiation. Key findings: Mitochondrial dysfunction precedes nuclear mutations in some cancers. Abnormal mitochondrial metabolism (Warburg effect) fuels tumor growth. Restoring mitochondrial function can suppress tumorigenesis in experimental models. 🌍 If cancer is fundamentally a disease of energy metabolism, this shifts therapeutic focus: From targeting mutated oncogenes to restoring cellular bioenergetics. From gene-editing approaches to modulating mitochondrial dynamics (e.g., using drugs that restore oxidative phosphorylation). This theory resonates with Otto Warburg’s hypothesis from the 1920s, now revisited with modern tools like metabolomics and bioenergetics profiling. 💬 Could targeting mitochondria revolutionize cancer therapy? Or is this a complementary avenue alongside genetic therapies? Let’s debate. #CancerResearch #Mitochondria #Metabolism #Oncology #Therapeutics #FutureOfMedicine

Treatment failure for the lethal brain tumor glioblastoma (GBM) is attributed to intratumoral heterogeneity and tumor evolution. We utilized 3D neuronavigation during surgical resection to acquire samples representing the whole tumor mapped by 3D spatial coordinates. Integrative tissue and single-cell analysis revealed sources of genomic, epigenomic, and microenvironmental intratumoral heterogeneity and their spatial patterning. By distinguishing tumor-wide molecular features from those with regional specificity, we inferred GBM evolutionary trajectories from neurodevelopmental lineage origins and initiating events such as chromothripsis to emergence of genetic subclones and spatially restricted activation of differential tumor and microenvironmental programs in the core, periphery, and contrast-enhancing regions. Our work depicts GBM evolution and heterogeneity from a 3D whole-tumor perspective, highlights potential therapeutic targets that might circumvent heterogeneity-related failures, and establishes an interactive platform enabling 360° visualization and analysis of 3D spatial patterns for user-selected genes, programs, and other features across whole GBM tumors. Interesting spatial biology study of glioblastoma development by Joe Costello and larger team at University of California, San Francisco Link to full paper: https://lnkd.in/ex4m3XA9

Your brain produces toxic waste every minute you're awake. Most people don't know it has a cleaning system. Or that the system only turns on during deep sleep. The glymphatic system is your brain's garbage disposal. Named for the glial cells that power it. Discovered in 2012. Completely changed how we understand brain health. Every thought you think, every memory you form, every movement you make creates metabolic waste. Amyloid-beta. Tau protein. Other toxic byproducts. During the day, these accumulate between your brain cells. At night, during deep sleep, the glymphatic system flushes them out: 1. During deep sleep, brain cells shrink by 60% ↳ Creates space between neurons ↳ Allows cerebrospinal fluid to flow through ↳ Sweeps waste toward blood vessels ↳ Carries toxins out of the brain 2. The process is remarkably efficient ↳ Increases waste clearance by 10-20 fold during sleep ↳ Clears amyloid-beta that would otherwise form plaques ↳ Removes tau proteins linked to neurodegeneration ↳ Essentially "takes out the trash" every night 3. But it requires specific conditions ↳ Deep, restorative sleep (not light sleep) ↳ Side sleeping position works best ↳ Proper cerebrovascular function ↳ Adequate sleep duration Chronic sleep deprivation keeps this system from working. Less than 6 hours per night. Fragmented sleep. Sleep apnea. Chronic insomnia. The toxic proteins accumulate. Amyloid plaques form. Tau tangles develop. Neuroinflammation increases. The exact pathology we see in Alzheimer's disease. As we age, the glymphatic system becomes less efficient. Blood vessels stiffen. Fluid flow slows. Waste clearance decreases. This explains why sleep becomes more critical as you get older. And why sleep problems in midlife predict dementia 20 years later. The brutal math: One night of poor sleep increases amyloid-beta by 5% in cerebrospinal fluid. Chronic sleep debt compounds this night after night. Brain imaging shows measurable amyloid buildup after weeks of poor sleep. In otherwise healthy young adults. Who cares? I ask every dementia patient about their sleep. I commonly hear about: - years of sleeping less than 6 hours - Untreated sleep apnea - Chronic insomnia - Shift work disrupting circadian rhythms What you can do: Treat sleep apnea aggressively. CPAP adherence matters more than any dementia drug. Prioritize 7-9 hours of actual sleep time. Not just time in bed. Maintain consistent sleep-wake schedules. Even on weekends. Address insomnia with cognitive behavioral therapy before reaching for sleeping pills. Your brain needs to clean itself. Every single night. 💬 How many hours of sleep do you actually get per night? ♻️ Repost if sleep is brain maintenance, not optional 👉 Follow me (Reza Hosseini Ghomi, MD, MSE) for science-backed strategies to protect your brain health

Stanford scientists have discovered that cancer cells don’t just use one trick to hide from the immune system—they use two separate “don’t-eat-me” signals to stop macrophages from killing them. The first signal, CD47, was already famous for acting like an invisibility cloak that tells macrophages to back off, and blocking it with an anti-CD47 antibody is already in human trials. In the Nature Immunology paper, the same Stanford team also found that tumors use MHC class I as a second stop signal by binding to a macrophage receptor called LILRB1, which suppresses the macrophage’s ability to engulf and destroy the cancer. When researchers blocked both CD47 and LILRB1 in mice, tumors rapidly filled with immune cells, shrank significantly, and became far easier for the body to clear. This shows that many cancers survive by running two overlapping escape systems, and turning off both “don’t-eat-me” pathways at once may dramatically boost the immune system’s ability to attack and eliminate tumors.

We and others have shown that #psychedelics can spark the growth of new synapses in the brain. But there are some deeper questions: where do those new connections actually go? Which specific neural pathways are modified? A new study from the lab is now online at Cell by Cell Press - In this latest work, rather than imaging one synapse at a time, we turned to a more powerful tool for circuit tracing: an engineered rabies virus 🦠, which naturally hops across synaptically connected neurons in the brain. Think of it like the Google Street View self-driving cars, but for neural circuits – roaming widely to show the connected cells in the entire brain.   In the experiment, mice received either #psilocybin or saline control, followed by rabies viral tracing and whole-brain imaging of fluorescently tagged neurons. The psychedelic-induced pattern of rewiring was far from random and revealed several insights:   1) Psilocybin weakens recurrent connections in the cortex, feedback loops that may contribute to the rumination of negative thoughts. 🔄   2) The drug strengthens pathways that carry sensory signals to deeper, action-driving brain regions, tightening the link between perception and behavior. 🎯   3) The circuit reorganization was influenced by neural activity. In a proof-of-concept experiment, we show that manipulating the firing activity can alter psilocybin’s rewiring patterns, demonstrate that it may be possible to sculpt the psychedelic-evoked structural neural plasticity. 💥🧠   We hope the results will change how we think about the therapeutic mechanisms of psychedelics. It is not just more synapses; it is about which circuits are remodeled. Moreover, we have some control over the drug-evoked plasticity when we pair it with neural activity modulation, providing a reason for trying to integrate psychedelics with something like rTMS.   This was a team effort spearheaded by Quan Jiang. With help from collaborators at Allen Institute, UC Irvine, and CUHK. The research was supported by One Mind and National Institute of Mental Health (NIMH).   Link to the paper: https://lnkd.in/eSDMdg5Q

Your immune system is not mine. And that changes everything. Exposed to the same virus, each of us produces a distinct antibody profile. Not just in quantity, but in precision: the regions of the virus we target, the proteins we recognize, the memory we build. Age, biological sex and genetics reach into the very architecture of how we respond to infections. A study just published in Nature Immunology, from teams at Institut Pasteur, CNRS and the Collège de France, makes this strikingly clear — and speaks directly to one of Pasteur 2030's growing research priorities: understanding how individual biological factors shape immunity and what that means for human health. The study analyzed antibodies from 1,000 healthy individuals against more than 90,000 viral protein fragments. Age alone accounts for over half of the variation in our antibody repertoire. Against influenza H1N1 and H3N2, younger adults target the variable surface of the virus while older individuals shift toward its stable core. Women and men mount different responses to the same flu strains, despite comparable vaccination rates. And against a shared pathogen, European and African cohorts produce antibodies targeting entirely different proteins — shaped by geography and exposure history. Each body writes its own immunological story. For decades, we have designed vaccines and treatments as if immune responses were universal. Integrating this variability — across individuals, populations, and geographies underrepresented in global research — is a rethinking of medicine's foundations. Congratulations to Lluis Quintana-Murci and all the teams behind this landmark work. #Immunology #Vaccines #PersonalizedMedicine 

📢 Excited to share our latest research published in Nature: "A human brain map of mitochondrial respiratory capacity and diversity"! 🔬 In collaboration with an exceptional team, we've developed an innovative approach to bridge cellular biology and cognitive neuroscience by mapping mitochondrial function across the human brain at neuroimaging resolution. 🧠 Key findings: Grey matter contains >50% more mitochondria than white matter. Mitochondria in recently evolved cortical areas exhibit specialized energy-transforming capabilities, aligning with the metabolic demands of human-specific cognitive functions. We created MitoBrainMap, a brain-wide atlas predicting mitochondrial characteristics from MRI data. 🌟 This work opens new avenues for understanding the mitochondrial basis of normal brain function and its implications for neurodegenerative, neurovascular and neuropsychiatric conditions. Explore the interactive MitoBrainMap here 👉 https://lnkd.in/dRiwBJex Full article: https://lnkd.in/dzS2zkMS Grateful to all collaborators and institutions involved! VBHI Columbia University CNRS Bordeaux University #Neuroscience #Mitochondria #BrainMapping #MRI #NaturePublication

🧠 As a neuroscientist, I find this absolutely incredible. The first-ever atlas of brain development has just been published and it’s nothing short of breathtaking. For the first time, researchers have mapped how stem cells transform into neurons during mammalian brain development, tracking hundreds of thousands of cells in humans and mice. They’ve identified when and how neural progenitors shift from building excitatory to inhibitory neurons and even how glial cells emerge over time. In essence, they’ve charted the biological choreography of the brain’s birth. This isn’t just a technical feat. It’s a window into the deepest question in neuroscience: ➡️ How does a collection of stem cells become a mind? Projects like the BRAIN Initiative Cell Atlas Network (BICAN) are changing how we understand neurodevelopment, disorders like autism and schizophrenia, and even how we model the brain in vitro. Every data point in this atlas carries potential for precision medicine, regenerative neuroscience, and the next generation of brain-inspired models. Truly a landmark moment. What a time to be doing neuroscience. 🧬 #Neuroscience #BrainDevelopment #StemCells #BRAINInitiative #Neurogenesis #Nature #ScientificDiscovery #Neurobiology

One week of short sleep in otherwise healthy adults. Not "sleep deprived" by strict definition. Just 4-5 hours a night. Testosterone dropped 15%. Insulin sensitivity dropped 20%. Muscle protein synthesis dropped 19%. Hunger hormones rose 28%. Cortisol rose 51%. These aren't the only systems affected. They're just some of the ones that have been measured in controlled settings. No supplement, no diet hack, no training program (crazy claim, I know, but you can't outrain poor sleep...) outperforms sleep at keeping systems "online". References: Leproult & Van Cauter, JAMA, 2011. Buxton et al., Diabetes, 2010. Zuraikat et al., Diabetes Care, 2024. Spiegel et al., Lancet, 1999. Saner et al., J Physiol, 2020. Spiegel et al., Ann Intern Med, 2004.

Metal-coordination bonds, a highly-tunable class of dynamic non-covalent interactions are pivotal to the function of a variety of protein-based natural materials like mussel byssal thread fibers or abrasion resistant arthropod mandibles. However, little is known about their fundamental behavior and what design principles are used in biological materials to create tunable, strong and tough materials. How is it possible to create resilient materials out of highly fluctuating bonds? In this paper led by Eesha Khare, and in collaboration with Kerstin Blank, David Kaplan and Niels Holten-Andersen, we study the intriguing mechanics of this class of bonds, focused specifically on size effects and a careful analysis of mechanisms using a joint computational-experimental analysis. We specifically explore an intriguing feature of biology's use of metal-coordination bonds, bond clustering, rather than relying on individual bonds. The work uncovered key binding motifs to produce strong, tough, and self-healing bioinspired materials for many potential applications in engineering. We rationally designed a series of elastin-like polypeptide templates with the capability of forming an increasing number of intermolecular histidine-Ni2+ metal-coordination bonds. Using single-molecule force spectroscopy and steered molecular dynamics simulations, we show that templates with three histidine residues exhibit heterogeneous rupture pathways, including the simultaneous rupture of at least two bonds with more-than-additive rupture forces. The methodology and insights developed improve our understanding of the molecular interactions that stabilize metal-coordinated proteins and provide a general route for the design of new strong, metal-coordinated materials with a broad spectrum of dissipative timescales. A highlight of this work was the amazing collaboration between four labs. Thank you Kerstin Blank for hosting Eesha Khare at the Max Planck Institute for Colloids and Interfaces where she did the experimental work! Paper: https://lnkd.in/ebYVPz3D Khare, E., Gonzalez Obeso, C., Martín-Moldes, Z., Talib, A., Kaplan, D. L., Holten-Andersen, N., Blank, K. G., & Buehler, M. J. (2024). Heterogeneous and Cooperative Rupture of Histidine–Ni2+ Metal-Coordination Bonds on Rationally Designed Protein Templates. ACS Biomaterials Science & Engineering. American Chemical Society https://lnkd.in/e-ANrjzM