Charles Warren

Eric Topol, MD, very well done! I was discussing this with one of my associates —LISA GREENFIELD, CAFS—and we discussed the urgent need for IAQ (indoor air quality) measurement solutions. Our bodies are regularly exposed to the smallest particles, some less than .016 nanometers, although many microplastics are larger and can pass into cells via cellular translocation. Those tiny particles can penetrate deeply into the body, often bypassing protective layers in cell walls through diffusion or transport. Once inside, they create tissue oxidation. These small particles can even pass the blood-brain barrier (as you've shown), sometimes hijacking small metallic particles to sneak past. Exposure to contaminants may lead to neurotoxicity, which is related to neurodegenerative diseases. Neurotoxicity has been reported in vivo after exposure to particulate matter, such as certain degraded microplastics, a significant finding that underscores the potential health risks associated with such exposure. In a study by Ziani et al. in 2023*, it was demonstrated that oxidative stress and the activation of brain microglia (immune cells) may be caused by direct contact with translocated particles, which are capable of passing through the cell wall in a process called translocation. Their research showed that microplastics can also indirectly and directly damage organs, tissue, and epithelial cells (in the respiratory, digestive, and CNS systems) through the action of circulating pro-inflammatory cytokines (from other inflammation sites), subsequently damaging neurons. Exposure to traffic pollution, including particulate matter, has been associated with mild cognitive impairment in the elderly, increasing the risk of Alzheimer’s disease development and a higher incidence of dementia (Ziani et al., 2023). Microplastics could contribute to the increasing incidence of neurodegenerative diseases through the same mechanisms depending on individual susceptibility. Indeed, in vivo toxicity testing has shown that microplastics can impact neuronal function and behavior (Ziani K et al., 2023). In the brain of European seabass (Dicentrarchus labrax), microplastics are reported to inhibit acetylcholinesterase (AChE), cause oxidative stress with an increase in lipid peroxidation levels, and increase the anaerobic pathway of energy production. (also Ziani K et al., 2023). *Ziani K, Ioniță-Mîndrican CB, Mititelu M, Neacșu SM, Negrei C, Moroșan E, Drăgănescu D, Preda OT. Microplastics: A Real Global Threat for Environment and Food Safety: A State of the Art Review. Nutrients. 2023 Jan 25;15(3):617. doi: 10.3390/nu15030617. PMID: 36771324; PMCID: PMC9920460.

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Excited to announce the 2025 Gordon Research Conference (GRC) on Protein Engineering, this second GRC on Protein Engineering will be held at Bryant University in Smithfield, RI from July 27th to August 1st 2025 https://lnkd.in/g-763SeF. please come join us if you would be interested in this exciting field. Different fields have experienced a transformative expansion in research distinction and capabilities. There now exists a strategic opportunity for protein engineering to take the lead and spearhead the integration of this joint effort, reflected by The Nobel Prize in Chemistry 2024. We believe that this GRC conference will create a gateway for the next generation of engineers and researchers, and will be a vehicle toward future development in the midst of an amazing convergence of multiple cutting-edge areas in protein engineering and its applications. Confirmed speakers include the Nobel Laureate Prof. Frances Arnold and distinctive scientists showing below: 1.            Fundamental Principles of Protein Engineering Possu Huang (Stanford University)/Frances Arnold (CalTech, Nobel Laureate)/Huimin Zhao (University of Illinois at Urbana-Champaign) 2.    Biosensors and Imaging Jennifer Prescher (UC Irvine)/Jin zhang (UC San Diego)/Robert Campbell (Tokyo University)/Nathan Shaner (UC San Diego) 3.    Rational Design of New-to Nature Proteins Jiri Damborsky (FNUSA-ICRC & Masaryk University, Czech Republic)/Joelle Pelletier (University of Montreal)/Sílvia Osuna (University of Girona & ICREA, Spain)/Koga Nobuyasu (Osaka Univ, Japan) 4.    AI for Protein engineering Zhongyue John Yang (Vanderbilt University)/ Jennifer Listgarten (UC Berkeley)/Doug Barrick (Johns Hopkins University) 5.    Biocatalysis and Industrial applications Carlos Martinez (Pfzer)/ Stephanie Galanie (Merck)/Zhi Li (National University of Singapore, Singapore)/Brent Dorr (Ginkgo Bioworks) 6.    Protein Engineering for Synthetic Biology Pimchai Chaiyen (Vidyasirimedhi Institute of Science and Technology (VISTEC), Thailand)/Weixin Tang (University of Chicago)/Jay Keasling (University of California, Berkeley) 7.    Directed Evolution for Enzyme Optimization Yang Yang (University of California Santa Barbara)/Leilei Zhu (Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, China)/Miguel Alcalde (Institute of Catalysis, CSIC, Spain)/Chang Liu (University of California, Irvine) 8.    Protein engineering for Immunotherapy and other diseases Anna Wu (Beckman Research Institute, City of Hope)/Xue Gao (University of Pennsylvania)/Bingfei Yu (University of Southern California)/Wilson Wong (Boston University) 9.    Repurposing Protein for Novel Chemistry and Applications Stefan Lutz (Codexis Inc)/Xiongyi Huang (Johns Hopkins University)/Xiaojing Gao (Stanford University)

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Human Microbiome and Immunity Numerous studies have demonstrated that the human microbiome, especially the gut microbiome, plays a key role in the development and function of the immune system. Trillions of microorganisms live in and on the body, helping to shape immune responses, defend against pathogens, and maintain immune balance. Therefore, this relationship between the microbiome and immunity is critical for overall health and disease prevention. As the first line of defense, the gut microbiome works by establishing a physical barrier and competing with harmful pathogens for space and nutrients. Beneficial microorganisms in the gut help regulate the activity of immune cells by stimulating them and ensuring a balanced immune response. This balance is essential to prevent overreactions, such as inflammation and autoimmunity, where the immune system mistakenly attacks the body's own tissues. Research has found that a healthy, diverse microbiome can promote a well-regulated immune system and reduce the risk of infection and inflammatory diseases. Conversely, an unbalanced microbiome, known as dysbiosis, can lead to decreased immunity and chronic inflammation. This has been linked to a variety of diseases, including allergies, asthma, autoimmune diseases, and inflammatory bowel disease (IBD). Research has also found that factors such as genetics, diet, antibiotic use, and environmental exposures can influence the composition of the microbiome and thus immune health. For example, fiber-rich and fermented foods support microbial diversity, while processed foods can disrupt the balance of gut bacteria and weaken immune function. Recent studies have shown that microbiome-targeted therapies such as probiotics, prebiotics, and fecal microbiota transplants (FMTs) can enhance immune health by restoring microbial balance. These interventions provide promising strategies for treating or preventing disease by supporting a strong and well-regulated immune system through microbiome management. It is foreseeable that further understanding of the complex relationship between the microbiome and immunity will open up new possibilities for personalized medicine and health optimization. References [1] Danping Zhang et al., Cell Research 2020 (https://lnkd.in/eKyuGir6) [2] Ji Youn Yoo et al., Microorganisms 2020 (10.3390/microorganisms8101587) #Microbiome #Immunity #GutHealth #ImmuneSystem #Dysbiosis #HealthyLiving #Probiotics #Inflammation #AutoimmuneDiseases #Nutrition #ScienceNews #HealthOptimization #PersonalizedMedicine

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Check out this beautiful video from @altM.bio that serves as a mini explainer, busting some of the biggest myths about biomaterials. It dives into the three most important aspects when choosing sustainable alternatives: quality, cost, and scalability. If you’ve ever had questions about biomaterials, this video answers them all in the most compelling way. Don’t miss it! #Biomaterials #SustainableInnovation #CircularEconomy #FutureOfMaterials #SustainableAlternatives #MaterialScience #GreenTech #EcoInnovation #SustainabilityMatters #ClimateAction #CleanTech #Bioeconomy #ResponsibleManufacturing #InnovationForSustainability #SustainableSolutions

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Grant revenue is not revenue. I'm all for non-dilutive funding, if and only if the SBIR/STTR-funded project accelerates your strategy with development of a product that will be sold (so science fair projects). However... *grant revenue is not validation dollars on the top line.* What you have shown is an ability to write grants, the basis for the research that led to the startup (in the case of academic spin-outs) in the first place. What you have not shown is 💸 the desire for customers to purchase your product(s) ➡ an ability to articulate a go-to-market plan, or 🔐 a down in the trenches understanding of product-market fit. Startups are a game of the quick and dead -- take the time and money you would spend writing these grants early in the life of your company and hit the road, listen to your customers, learn where and how your products fit, and start selling. Your P&L shows me your real progress there -- As an investor and advisor, I would rather see $10,000 in revenue from sales from a handful of customers in 2 quarters than a X% chance you get a $1M grant in 9 months.

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Stellantis's outgoing CEO shows that nobody is as good or as bad as they are made out to be. That's why it's critical to take into account whether there were tailwinds, special chemistry with peers, or other factors that were attendant to success. A lot of the work that goes into quantitatively understanding the success of companies works the same way. In the 1950s, economists worked hard to disentangle the behavioral aspects of running a company from the financial aspects of how the company performance was perceived and understood by the market. Modigliani, Miller, Merton, Cyert, Simons and others spent a lot of time on foundational thinking: how do you know what matters, and how can you price it? For example, Merton realized that one way to think about corporate debt (aside from taxes etc.) was in terms of a combination of treasury bonds plus a short put option on the assets of the company. Essentially, a company's ability to pay off its debts is the likelihood that they would be forced to liquidate the company if the total value of the company dipped too low. This kind of thinking fueled the transition from balance sheet thinking strategy that James O. McKinsey pioneered 80 years ago to the modern forms that BCG and McKinsey have developed over the last 40 years. If we can tease apart the behavior of the firm from the perception of the performance of the firm, and we can show that some things are more often seen in the top 10% performers, perhaps there is a consistent economic and management basis for high performance. The thing is, the most important parts of these models are inconvenient to deal with. Treasury bond yields change all the time. Consumer purchasing power changes, consumer relative preferences all shift and flow unevenly. It's super hard to collect and calibrate all these factors to tease out what managers really did, and whether they were responsible for the company performance. It's even harder to sell those insights because by the time you have enough calibration to be convincing to a third party, the value of that information has likely decayed quite a bit. Do you even remember Lee Iacocca? I bet a lot of you don't! Stellantis is a prisoner of decades of poor decision making, lousy labor relations, and a delusional belief that they deserve to exist. Did the Nissan playbook make sense to deploy there? For every Ghosn, there is an equal and opposite reGhosn. That's why I think McKinsey's pivot away from numbers and "beyond the hockey stick" thinking, and towards basics of leadership was a smart move to sell. You have to sell information that doesn't exist yet. That's what the right leader ought to accomplish for the right firm. Don't be encumbered by the past, go off and do something wonderful.

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I had plans for today, but made the 'mistake' of perusing the FDA website. And the song "What's goin' on?" came to mind [See COMMENT SONG added below.] My reflexive read was that 'Wedgewood' is tablewear. As may be, the image below is from a 483 reply from a domestic US compounder, dated 07 DEC 2023. What's going on indeed - this is from almost a year ago. As noted yesterday, compounders are a current topic - right Luis Charles Chavarría, Neil Di Spirito and Joel Russo M.S., CQA , among others? (cf: https://lnkd.in/e85ThAdT ) All 15 pages will make interesting reading, I think - and when you get to the signatures, legal counsel seems to be missing. ("What's Going On' again?) The responses cover 7 observations - and the first one in the image below is certainly familiar. I leave them to your reading if you care to - and for those newish to this, I find this a reasonable template. (Others may disagree.) BUT my second key point is how much else was on the same page / table. (See COMMENT TABLE for the image.) Quite a collection of correspondence - I don't have time to review it; another time for that. Here's the link to the response - enjoy the day (unless you root for the NY Yankees ....) URL: https://lnkd.in/e-ejmFS9 #fda #drugcompounding #sterileproduct #AQL #503B #California

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This week we’re scheduled to get some clarity on FDA’s Elevidys Accelerated Approval. There are three main categories that the FDA is due to weigh in on – each precedent-setting in its own way: The first is whether the current narrow Elevidys label will be expanded beyond 4- and 5-year-old Duchenne patients. Recall, the EMBARK Confirmatory trial enrolled patients ages 4-7. Sarepta’s sBLA submitted in December ‘23 also included some early subset data from ENVISION (and older supporting data from ENDEAVOR) that could potentially support age expansion. Sarepta has treated patients as old as 25 years old with Elevidys in the context of clinical trials. Sarepta believes their Elevidys label should be age agnostic. The second is whether Elevidys will remain on market with Accelerated Approval or be converted to a full approval, at least for the 4-5 year olds. Recall, whether granted access to the market via accelerated approval or full approval, the price is likely to remain $3.2M. Sarepta does not appear to be discounting or offering outcomes-based agreements or warranties so $3.2M is probably the actual price tag (with Sarepta making minor pricing concessions to distribution channels). Finally, because the sBLA included supporting subset data from ENDEAVOR and ENVISION, Sarepta is asking for removal of the ambulatory requirement that is currently in the Elevidys Accelerated Approval label. Alas, analysts see the evidence for efficacy in non-ambulatory patients as too limited and preliminary to warrant approval. But time will tell. Since back in the Garabedian days, I’ve learned to never bet against Sarepta. If Sarepta gets all that it has asked FDA for, after this week, Elevidys’ will have full approval with a label open to all age Duchenne patients, regardless of ambulatory status. But that scenario is unlikely; the FDA response will probably be more mixed than binary. However, any expansion of label has implications for payers, as more patients from the prevalent Duchenne population would have access immediately. And at $3.2M per patients, insurers, reinsurers and self-insured employers will be watching because...$3.2M here and $3.2M there and pretty soon you’re talking real money. Sarepta has assured the investment and patient community that it is ready to meet product demand, regardless of how the FDA chips fall. So there you have it.  We should know by week's end. #sarepta #elevidys #cgt #atmp #acceleratedapproval #reinsurance #duchenne

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I shared it before, but this guide is so good on magnetic beads that is worth for you to take a look: Magnetic beads (or superparamagnetic particles) are versatile little tools for easy and effective isolation of biomolecules. Read Magbeads 101: A guide to choosing and using magnetic beads, to compare the different surface chemistries and find the best bead for your application. We have a bead for every need! https://cytiva.link/altrz

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👀 What could researchers understand if they could actually see their cells flickering through a flow cytometry laser via real-time, identifying snapshots, like high school students filing by for their yearbook portraits? 📸 And what if we had the technology not only to photograph the cells at high speeds, but to help us categorize those images automatically and identify underlying patterns?  ✨ Now, we do via AI-powered automated image analysis.  https://lnkd.in/eyrQ4Xpt #AttuneCytPix #AI #FlowCytometry

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Trust your team, and enable them to do great work. I was fishing in Rhode Island recently 🎣 (can't give up spots, or I'll walk the plank) and saw these beautiful old ships. It must have been wild to get a whole bunch of crew together, navigating by the stars to get 'East'. No wind instruments, weather forecasting, GPS location....nothing. It's you, your crew, the stars, and some hand drawn map. Similar to startup #biotech companies, the captain is capable of performing many jobs, but a tight ship has a captain who delegates: the skipper, and each crew member who is trusted to do their job because everyone is counting on them. Similar to a biotech, they're rationing their food (cough* latest series of funding), until they can restock at the next port (I suppose the port is a VC 🧐 ). Will I be like the other ships that ended up on the rocks? Will we make it to the next port? Will I still be on the ship when we make it? There are a whole bunch of things that need to go right, and everyone has a job to do. Among these folks is the rockstar MacGyver person. The person who seems to move mountains for the team. This 'MacGyver', tends to shoulder the load stoically, and rarely asks for help. These are the kind of people that like having extra work, as they can feel the the impact they're making on the team, but 'coiling rope' isn't exactly making the ship go faster. I see this frequently in startup biotechs, where the MacGyver is on a bunch of side quests (that they're capable of), but their time isn't well spent. e.g. the bioinformatician, who's manually curating data, or pulling data for the wet lab team every time they need to run an analysis. It's up to the leaders to enable their team to make the best impact on the organization, but also on the superstar to recognize that although some work may be helpful, but their skills would be a game changer elsewhere. My 2 cents for the day: a lot of people are unaware or don't ask for help, and reading between the lines as a leader will forge rockstar teams.

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Building new molecules is a challenge. A new AI tool is changing that by designing molecules piece by piece with a fragment-based approach.

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Every day our customers surprise us with new ways to do more advanced tests in a POC format. Please read this new blog post: Key breakthroughs in molecular POC testing Learn more about the emerging technologies used and the sample preparation techniques that are key to ensuring their success. Learn more: https://lnkd.in/e4qQB4a6

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Brad Hightower, I enjoyed reading both your prior posts, the one on Patient Centricity as well as the internet is not real post. To be honest the big question is "What does Patient Centricity mean?", and despite what the "Clinical Trial Influencers" and some Startup CEOs will tell you, it is about getting patients insights into development of therapies not just input into a single trial. It is also about making sure where possible we can avoid/minimize additional burden on patients for taking part in the trial. Can we argue against that? I completely agree with your point on crappy protocols, though.

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I really like this post from Eric, very important concepts to think about organizational design for future. This is all skills (technical and people) listed in one snapshot. We all get focused on today but harder to see over the horizons and pay attention to the changes that are going to drive the economic growth for any business. Thank you Eric for sharing!!! Love this table and this my kind of thinking because it is so important to build skills in the teams!! #future #growth #employers #employees #human resources #orgnizational design #AI #skills #Systems #cyber security #data #digitalization

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Do Gametes (Egg/Sperm) Create a Sex Binary? Science Says No. https://lnkd.in/gdbf_Atk Some people who don't understand that biological sex is created by a constellation of traits will ask, do gametes (egg/sperm) create a sex binary? The answer is that gametes cannot be used to create a sex binary in humans, because no gametes can be present along with ambiguous gonadal tissue. This third “undefined” possibility eliminates the possibility for a binary sex classification. Furthermore, gametes are well known to mix-and-match with other sex traits—commonly, chromosomes, genitals, sex hormones, and secondary sex characteristics—making them one of multiple sex markers that in aggregate constitute a person’s sex as female, male, or a blend of both (intersex). Key Takeaways: 1. Gametes cannot be used to create a sex binary in humans, because no gametes can be present along with ambiguous gonadal tissue. 2. This third “undefined” possibility eliminates the possibility for a binary sex classification in humans. 3. Gametes are only one of multiple sex markers that in aggregate constitute a person’s sex as female, male, or a blend of both (intersex/undefined). 4. Other critical sex markers beyond gametes include but are not limited to gonads, genitals, chromosomes, sex hormones, and secondary characteristics. No sex marker, including gametes, present as a sex binary. https://lnkd.in/gdbf_Atk What questions or comments do you have about biological sex (or gender) spectrum? Ask them in comments below. #science #lgbtqia #lgbtqiacommunity #intersex

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Empowering Teams with Adaptive Leadership Today, adaptive #leadership is super important. It’s not just about changing our styles; it’s about #empowering our teams to share their thoughts and ideas. When we move away from a #top-down approach and encourage autonomous teams, everyone feels valued and motivated. By focusing on outcomes instead of micromanaging, we let our teams take ownership of their work, which drives #engagement and sparks innovation. Using key performance indicators (#KPIs) can help guide our teams while still giving them the freedom to find their own path to success. The leader sets the structure and ensure the team has the support that need to thrive. It’s also crucial that everyone knows how their work fits into the bigger picture and the organization’s goals. Let’s keep pushing for adaptive leadership, open dialogue, and making sure every voice is heard. How do you empower your team while fostering their independence? I’d love to hear your thoughts! 💬 Nice reading —> https://lnkd.in/gGgrsGcg #AdaptiveLeadership #EmpowerYourTeam #LeadershipMatters #TeamAutonomy #OutcomesOverMicromanagement #InnovativeLeadership #LeadershipDevelopment

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The Silent Tutors: How LLMs Are Bridging Knowledge Gaps in Cell Therapy Manufacturing

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