Science

Wrapped up my latest visit to New York City, and it reaffirmed a vital truth: the iconic skyline, while breathtaking, also represents a significant carbon challenge. As buildings contribute over two-thirds of NYC's emissions, their transformation is crucial to achieving the ambitious 2050 goal of an 80% reduction.   Digital technologies offer a feasible and cost-effective solution. Consider these numbers:   Digital building management alone can achieve 42% emission reduction in offices, with payback periods of less than three years. Electrification and microgrids with renewable energy sources can further reduce emissions by 28%.   The combined impact? 70% reduction in operational carbon emissions. Achievable today, with a quick return on investment.   Now, imagine the impact at scale: New York City's iconic skyline, gleaming with clean energy. Let's make it a reality.

What is driving my cancer? From the patient perspective there are only two types of cancer, the ones we survive and ones we don’t.  In the USA alone, two million people are annually diagnosed with cancer and over half a million will die.  The fundamental reason for poor outcomes is that the diagnosis is often incomplete. A biopsy allows a pathologist to confidently say a cancer is present. We say we have made a “diagnosis” of cancer. However, until we understand what molecular event "drives" the patient’s cancer, all we can offer is non-specific treatments - surgery, radiation, and chemotherapy.  While effective for some, these treatments are associated with substantial and often long-term toxicity.  The biggest problem, however, is that these treatments are just not effective enough. When we can answer the question “what is driving my cancer” treatment outcomes are transformed. A cancer driver is a biological event that is only present in the patient’s cancer cells and not in normal cells.  This translates into precise treatments that are more effective and less toxic.  There are already good examples of precise treatments based on a deeper understanding of what drives cancer such as HER2 positive breast cancer (Herceptin), EGFR mutant lung cancer (Tagrisso), hereditary cancers due BRCA1 and 2 mutations (Lynparza). The problem is that these drivers are only present in a minority of cases.  We are still left with very large numbers of patients without an identified cancer driver - these cases often have diagnostic labels that underscore our diagnostic ignorance. “Triple negative breast cancer” and “non-small cell lung cancer lacking a driver mutation” are sad examples. These tumors have drivers, they just have not been identified. Why do we fail to identify cancer drivers in all cases of cancer? One fundamental reason is that molecular diagnostic methods are often compartmentalized. Each test examines the corrupted biology present in cancer cells at only one level, a DNA-only test, an RNA-only test, or a protein-only test.  This is not how the cancer cell works – the information flows from the abnormal DNA into RNA which drives abnormal protein expression.  It is largely the abnormal proteins that are the cancer drivers. Most new drugs target proteins in precise ways but current techniques do not measure protein expression in cancer cells in sufficient depth or scale to diagnose the cancer driver in every case. I am therefore devoting the next phase of my career to the development and application of proteogenomic techniques to standard pathology slides, with integrated analyses of DNA, RNA and Protein. Every hospital in the world holds a museum of cancer specimens in their pathology departments gathering dust.  Clinical Trial organizations have millions of them. We need to apply proteogenomic technologies at scale to improve treatment for future generations of cancer patients. I am looking forward to posting my progress on this vision!

What if your brain and immune system are the real keys to longevity? 🔥 Just out in Nature Medicine 🔥 “Plasma proteomics links brain and immune system aging with healthspan and longevity” by Hamilton Se-Hwee Oh, Tony Wyss-Coray, Anne Brunet, Michael Greicius & colleagues We often talk about aging as a slow, systemic decline ; but what if the real story is about a few crucial organs pulling the strings? We've been studying how immune system aging drives systemic decline for almost 2 decades and reading this elegant paper reaffirms this claim. In this massive study of ~45,000 people from the UK Biobank, Tony's group built machine learning models that estimate the biological age of 11 organs from plasma proteins. 🧬 Key insights: ✅ Each organ ages independently —> brain and immune system stand out ✅ Aged brains increase Alzheimer’s risk as much as carrying an APOE4 allele ✅ Aged immune systems drive mortality and chronic diseases ✅ Youthful brains and immune systems reduce mortality risk by nearly 60% ✅ Individuals with both youthful organs had the lowest death risk of all (HR = 0.44) ✅ Plasma proteomics tracks aging better than existing clinical clocks (like PhenoAge) 💡 The promise for longevity: If we can measure, protect, and intervene on the aging of specific organs — especially the brain and immune system — we might delay chronic disease and extend healthspan. Massive kudos to the phenomenal team across Stanford, the UK Biobank Pharma Proteomics Project, and the Wu Tsai Neurosciences Institute for making this possible. A milestone in translational aging science! BRAIN AND IMMUNE SYSTEM YOUTH PREDICT LONGEVITY #longevity #aging #biomarkers #proteomics #brainhealth #immunology

Proteogenomics refers to the integration of mass spectrometry-based proteomics with genomics, epigenomics, and transcriptomics next generation sequencing (NGS) data. This multiomic approach to translational research allows for novel insights into existing and future drug targets for the development of more effective and precise cancer treatments. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has performed proteogenomic characterization of over 1,000 treatment-naive primary tumors spanning 10 cancer types. A new study by Sarah Savage and larger team at the Baylor College of Medicine integrates the CPTAC dataset with other public datasets to provide insights into existing cancer drug targets while systematically identifying new candidate targets. Their team created a convenient web app to explore the dataset here: https://lnkd.in/efSKFxsj Pan-cancer proteogenomics expands the landscape of therapeutic targets. https://lnkd.in/e8w5Fcfx Methods overview: The authors analyzed harmonized CPTAC proteogenomics data from 1,043 tumor and 524 normal tissue samples across 10 cancer types. Drug target information was collated from DrugBank, Guide to Pharmacology, Drug Gene Interaction Database, and the in silico human surfaceome and classified into 5 tiers Integrative analysis of proteogenomics data and genetic screen data was used to identify synthetic lethal partners of genomically altered tumor suppressor genes. Neoantigen analysis was performed using the NeoFlow pipeline to identify mutation-derived neoantigens. A computational pipeline was developed to identify tumor-associated antigens as targets for immunotherapy Results overview: Proteomic analysis quantified 2,863 druggable proteins, which showed a wide range of abundance and heterogeneous mRNA-protein correlations across cancer types. Integration of proteomic and cell line data identified 51 pan-cancer targetable dependencies driven by protein overexpression and 31 driven by protein hyperactivation Evaluation showed the predicted targets were enriched for approved or investigational oncology drugs and could increase the success rate of identifying effective drugs by 2.6-fold. Integration of proteogenomics and cell line data revealed protein dependencies associated with loss of tumor suppressor genes like TP53, providing a strategy to target tumor suppressor loss Neoantigen analysis prioritized mutant KRAS peptides as promising public neoantigens. Computational prediction followed by experimental validation identified broadly applicable tumor-associated antigens as potential immunotherapy targets

🔬 Overcoming hurdles in mRNA therapeutics, scientists have developed a second near-infrared (NIR-II) lipid nanoparticle (LNP) approach to enhance mRNA delivery efficiency using a stimulus-responsive photothermal-promoted endosomal escape delivery (SPEED) strategy. 🌡️ How does it work? In the acidic endosomal environment, a specially designed pH-activated NIR-II dye-conjugated lipid (Cy-lipid) within the LNPs is protonated, turning on NIR-II absorption for light-to-heat conversion under 1064 nm laser irradiation. This heat triggers a change in the LNPs' morphology, promoting their rapid escape from the endosome. 📈 The result? Around a 3-fold increase in the translation capacity of enhanced green fluorescent protein (eGFP) encoding mRNA compared to the group without NIR-II light. Moreover, the bioluminescence intensity in the mouse liver region, induced by delivered luciferase encoding mRNA, showed a positive correlation with increasing radiation dose, validating the SPEED strategy. 🚀 This innovative approach offers a promising formulation strategy for the efficient delivery of therapeutic mRNA drugs with enhanced translation capability and therapeutic efficacy https://lnkd.in/eTsYEGYh #mRNATherapeutics #NIRIILNPs #DrugDelivery #SPEEDStrategy #Innovation #nanomaterials #nanoscience #nanotechnology #lipidnanoparticles #LNPs #strategy #work #translation

😩 Did you know that it can take 50 years to reabsorb deforestation emissions? 🌲 Yes, you heard that right. When we cut down forest, it takes up to 50 years for those new seedlings that we plant to offset that deforestation with, to reabsorb the damage. 🛍 I'm a fan of all solutions - and when I buy carbon or biodiversity credits to offset some of Climate Collective's work travel, or compensate for our family's outsized carbon footprint (living in North America puts us in the top bracket globally) I buy a mix of things. 🛠 That means avoidance, reductions and removals solutions, as they are all needed, and fill different parts of the complicated mosaic that is decarbonization. Recently, I've grown a bit concerned about the debate around avoidance credits, where many people argue they are ineffective.. This is worrisome as avoidance credits are critical to strengthen the work to avoid deforestation. To me, the benefits of preventing carbon emissions before they happen, versus undoing emitted carbon dioxide (CO₂) become enormous at the needed gigaton scale: trillions in investment today prevents quadrillions spent on disaster relief. Leah Ellis for World Economic Forum put it well:  "There are three ways of addressing a broken gushing faucet: you can fix the tap, put a bucket under the leak, or mop up the resulting water off the floor." Avoidance is fixing the tap. This means two things: - investing in the development and deployment of carbon avoidance technologies, which produce the goods and services the world’s population needs without emitting more CO₂ - doubling down on nature-based carbon avoidance projects, particularly projects that avoid deforestation Why is avoiding deforestation so important? Well, you read my headline. Paraphrasing Steve Zwick, who pulled this example from a 2019 paper from Nature: One hectare of deforestation emits 355 tons of CO2 (all at once). One hectare of reforestation absorbs 6.7 tons of CO2 per year. ⏳ That means it will take 50 years for newly planted trees to reabsorb the carbon released by every hectare deforested today. Many times, the most impactful thing we can do is to not do anything. Avoid the impact so we don't have to clean up its mess. Are you buying carbon credits for your organization or personal footprint? Carbon credits are a really powerful tool to channel investments towards cost-effective climate action, in areas where it can have the highest impact. Having worked across these markets since 2007 I know they are far from perfect - but personally I'm committed to supporting the emergence of a new generation carbon markets, where digital tech and data unlocks high-integrity climate action. 🌱 I invite everyone to join me. Do what you can, how you can. But please do something.

Especially in the field of dementia care and support where our emotions, mental state, and demeanor directly affect the person living with dementia, how caregivers in a team setting FEEL is foundational to how residents also feel. One of the cardinal rules of working on our team is that we do not have unresolved conflict with one another. We really work hard at it, and as leaders we always have the mindset of “we build and maintain trust.” In other words, we facilitate healthy conflict resolution - not just reactively but proactively to build and keep positive rapport between teammates. The primary reason is that many people living with later-stages of dementia have diminished abilities in social cognition. Social cognition is what allows us to have context in social situations. We process, remember, and reference information from past social experiences to help us understand and predict the behaviors of others and our own. A simple example is when you walk into a room and you sense tension between the two other people in the room. Prior experience and context clues let’s us understand: - they’re in the middle of a heated conversation - they are friends - I should politely exit when I can - I won’t leave abruptly so as to make it awkward for them - They know that I know I sense tension - They otherwise seem to be safe; it’s just awkward and they need a moment Then we might diffuse the added dynamic of a third person in the room and choose to leave the room by saying, “oh, I forgot my coffee mug at my desk. A sign that I really need my coffee to even think straight!” A person without social cognition abilities might walk into that same situation and: - not understand where the tension is directed - think or say, “what did I do wrong?” - start to feel unsafe - say the “wrong” thing On a dementia care TEAM, think of how often an understaffed, overworked, and emotionally unregulated environment could wreak havoc on a group of people with little to no social cognition. We can’t just be okay with writing care tasks as their sole job responsibilities. We have to teach and expect commitment to an emotionally regulated care environment. We have to teach leaders how to perceive and resolve conflict on the team. “I don’t come to work to make friends. I come to do a job and go home” and “I hate dealing with drama. We’re all adults” are both red flags on our team. 🚩 This mindset isn’t just about residents. These skills help everyone involved. As an industry we talk a lot about outcomes. We should really be talking about our inputs first. #dementia #seniorliving #memorycare

New from me - the FDA has cleared an AI algorithm that, when used with a digital stethoscope from startup Eko Health, can detect a key risk factor for heart failure. The algorithm was originally developed by the Mayo Clinic for use with electrocardiograms, but as adapted by Eko, it can be used by primary care physicians during routine checkups. Which means that early signs of heart disease might be caught before any symptoms emerge. “These tools are incredibly powerful — they help us screen for conditions for which we have treatments," Mayo Clinic cardiovascular head Paul Friedman told me.

A secret weapon to creating longevity of life is to exercise your mind. We all have known about working your body. But it's equally important to be relentless about working your mind. The hard truth is that this is a hard habit to develop for most people by the time they realize they need to do so. For those of you who are young enough to aggressively develop this habit, please... START! 1. Read (books, not just captions) 2. Explore subject matters laterally and vertically 3. Create and build Si Ramo, who was my mentor and founder of TRW (now Northrop Grumman), lived until he was 103. In his early 80s, Si was an active mentor to me when I as NASA Administrator. He kept up with the latest space business news and provided very focused suggestions. He also engaged the media where he could be helpful. In his 90s, he and I met for lunch once a quarter and enjoyed engaging in conversations about music, technology, politics and the state of our nation. We'd also go out on double dates with our wives and the four of us would always be the last ones left in the restaurant. Si Ramo also received a patent at 100. I have another (best) friend Bob who is my age. In his 70s, he got his photography collection of translucent composites into the Smithsonian. In his 80s, he completed a masters thesis on epidemiology at the University College London. So many people spend thousands to millions to focus on the financial part of retirement planning. But they seem to forget the things that cost nothing and will provide infinite return!