Radically different
Nature Medicine, Published online: 07 July 2026; doi:10.1038/s41591-026-04511-6
Multiomics profiling of extracorporeal cross-circulation with gene-edited pig liver xenografts in four human decedents provides comprehensive information on immune, coagulation and metabolic parameters that will help in the clinical development of this strategy for delivering hepatic support to patients with liver failure.
Scientists from the Cedars-Sinai Board of Governors Regenerative Medicine Institute, including investigators from the Cedars-Sinai Biomanufacturing Center, say they will share groundbreaking discoveries and discuss new frontiers in research at ISSCR 2026. The annual meeting of the International Society for Stem Cell Research will take in Montreal from July 8–11.
The Cedars-Sinai Center for Space Medicine Research has taken a special interest in biomanufacturing in space. It studies how microgravity aboard the International Space Station and other space platforms can be used to manufacture higher-quality biomedical products.
Researchers investigate the production of stem cells, organoids, engineered tissues, exosomes, and biopharmaceuticals, taking advantage of the reduced effects of gravity on cell growth and three-dimensional tissue formation.
The center collaborates with NASA, commercial space companies, and biotechnology partners to determine whether space-based manufacturing can yield therapies with improved quality, consistency, and function. Its long-term goal is to translate discoveries made in space into scalable manufacturing methods that advance regenerative medicine, drug development, and personalized healthcare on Earth.
At the upcoming ISSCR 2026 meeting, Arun Sharma, PhD, director of the Center for Space Medicine Research, will participate in a session co-sponsored by Cedars-Sinai on regenerative medicine in low Earth orbit. The focus of Sharma’s talk is accelerating development of organoid-based disease modeling and stem cell therapies due to increased access to microgravity, as well as in-space biomanufacturing.
Avinash Srivastava, PhD, a biomedical scientist in the Cedars-Sinai Biomanufacturing Center, is presenting information on the center’s proprietary integrated induced pluripotent stem cell biomanufacturing platform. The platform integrates standardized manufacturing with advanced bioprocessing to facilitate the scalable production of high-quality engineered cell therapies.
Dhruv Sareen, PhD, associate professor of Biomedical Sciences and founding director of the Cedars-Sinai Biomanufacturing Center, is presenting research on the integration of an in situ seed plating system into the center’s manufacturing workflow to streamline production of complex induced pluripotent stem cell lines for clinical-grade and research use.
The post Biomanufacturing in Space to Be Key Topic at ISSCR 2026 appeared first on GEN – Genetic Engineering and Biotechnology News.
It has never been more difficult for employers to offer health insurance for their workers. That’s especially true for America’s small businesses, the backbones of entire communities. More and more, they’re giving up entirely.
America’s employer-based health insurance system — the dominant form of coverage for people younger than 65 — is crumbling. The percentage of working-age adults who get their health coverage from a job has declined from 67% in 1998 to about 60%. It’s also more expensive than ever. STAT interviewed dozens of people across the country as part of a series that probes how and why this is happening. Panic, despair, and anger are most apparent among smaller shops and firms.
Small business owners and workers feel as though most, if not all, of their options are unaffordable, especially if they have plans with high out-of-pocket costs. Rising premiums — driven by high prices for hospitals, doctors, and prescription drugs and more intensive care — are eating into bottom lines and paychecks. Desperate companies are getting rid of traditional health benefits at an unprecedented pace. This shift is fraying the uniquely American expectation that jobs come with protection for injuries and illnesses — an expectation that is the product of World War II wage controls, industry opposition to government health care, and the biggest break in the tax code.
Public health advice has long emphasized exercise: move more, meet weekly activity targets, reduce time spent sitting. But a growing body of evidence suggests that the pattern of inactivity may also matter. Sitting for long, uninterrupted periods may not carry the same health implications as the same amount of sedentary time broken up by movement.
A new study published in PLOS Medicine adds cancer outcomes to that discussion. Researchers analyzed accelerometer data from 91,292 UK Biobank participants who wore wrist activity monitors for seven days and were then followed for a median of more than 12 years. The study found that prolonged sedentary behavior was associated with higher risk of cancer mortality and cancer incidence, while interrupted sedentary behavior showed the opposite pattern.
Sedentary behavior includes waking activities such as sitting, reclining, or lying down that require very low energy expenditure. Most guidelines and public health messages focus on total sedentary time. That is understandable: total sitting time is easy to communicate and has been repeatedly linked to poor cardiometabolic outcomes.
But the new study asks a more precise question: does it matter whether sedentary time happens in long blocks or is regularly interrupted?
The researchers defined prolonged sedentary behavior as bouts lasting at least 30 minutes in which at least 90% of the time was sedentary. Interrupted sedentary behavior included shorter bouts or sedentary periods broken up by movement. This distinction allowed the team to examine not only how much time people spent inactive, but how that inactivity was distributed throughout the day.
Each additional hour per day of prolonged sedentary behavior was associated with a 9% higher risk of cancer death. Prolonged sedentary time was also associated with higher overall cancer incidence, obesity-related cancers, and type 2 diabetes-related cancers.
Interrupted sedentary behavior showed an inverse association across the same outcomes. In other words, sedentary time that was broken up by activity was not linked to the same pattern of risk as long, uninterrupted bouts.
The authors summarize the implication clearly: “These findings suggest that not only the total amount of sedentary time, but also how sedentary time is accumulated, may be important for cancer risk.”
This matters because sedentary behavior is widespread and often built into modern work, transport, and leisure routines. For many people, the practical question is not whether they can avoid sitting altogether, but whether they can interrupt long sitting periods often enough to reduce risk.
The study also used substitution models to estimate what might happen if sedentary time were replaced with different types of activity. Replacing one hour per day of prolonged sedentary behavior with light physical activity was associated with a 12% lower risk of cancer death. Replacing 30 minutes per day with moderate physical activity was also associated with lower cancer mortality risk.
That finding is important because light activity is more achievable for many people than structured exercise. Standing up, walking slowly, doing household tasks, or taking brief movement breaks may not feel like “exercise,” but they may still interrupt metabolically harmful patterns of prolonged inactivity.
As the authors note, “light movement shouldn’t be ignored.”
The biological rationale is plausible. Experimental studies have shown that breaking up sitting with short activity bouts can improve glucose and insulin responses compared with uninterrupted sitting. Prolonged sedentary time may also contribute to low-grade inflammation, impaired immune function, insulin dysregulation, and ectopic fat accumulation—pathways that have all been discussed in relation to cancer risk.
The study has important strengths. It used device-measured activity rather than self-reported sitting time, reducing recall bias. It also followed participants for more than a decade and included multiple cancer outcomes.
Still, the findings should be interpreted carefully. This was an observational study, so it cannot prove that prolonged sitting directly causes cancer or cancer death. UK Biobank participants are also known to be healthier and more physically active than the general UK population, which may limit generalizability. Activity was measured over only seven days, and the monitors could not capture the context of sedentary behavior, such as whether someone was sitting at work, watching television, driving, or resting because of underlying illness.
The authors also note that residual confounding cannot be ruled out. People who sit for long uninterrupted periods may differ from others in ways that are difficult to fully measure, including occupation, frailty, health status, or broader lifestyle patterns.
Cancer prevention is often framed around smoking, alcohol, diet, body weight, vaccination, screening, and exercise. Sedentary behavior is increasingly part of that picture, but this study suggests the message may need to become more specific.
The goal may not only be to reduce total sitting time, but to avoid accumulating that time in long, uninterrupted blocks. For public health, that is a potentially actionable target: movement breaks at work, walk-and-talk meetings, standing transitions, household activity, or brief light-intensity movement after long periods of sitting.
The study does not suggest that movement breaks replace established cancer prevention measures. Nor does it mean that every hour of sitting carries the same risk for every person. But it does support a more nuanced view of inactivity: the body may respond differently to sedentary time that is regularly interrupted than to sedentary time accumulated in prolonged bouts.
As activity monitors become more common and prevention science becomes more personalized, cancer prevention advice may eventually move beyond broad exercise targets toward daily behavior patterns. For now, the message is simple enough: long sitting spells may be worth breaking, even with light movement.
The post Why Long, Uninterrupted Sitting May Matter for Cancer Prevention appeared first on Inside Precision Medicine.
Researchers at the University of California San Diego have uncovered the structural mechanisms that cause congenital myasthenic syndromes (CMS), revealing mutation-specific treatment strategies and identifying an existing antidepressant as a promising candidate for drug repurposing.
The study, published in Nature, explains how disease-causing mutations alter the human acetylcholine receptor (AChR), the protein responsible for converting nerve signals into muscle contraction. The findings also provide a framework for developing precision medicines tailored to the specific mutation carried by individual patients.
CMS is a rare inherited group of neuromuscular disorders that typically appears at birth or early childhood. Mutations in the AChR impair communication between nerves and muscles, leading to muscle weakness, difficulty walking, breathing problems, and, in severe cases, paralysis or death. Although more than 50 disease-causing mutations have been identified, the molecular mechanisms underlying these disorders have remained largely unknown.
To address this question, the investigators determined 12 high-resolution structures of representative mutant AChRs with and without therapeutic compounds. By combining these structural data with functional studies, they identified common mechanisms that explain the two major forms of CMS.
Fast-channel CMS is caused by loss-of-function mutations that reduce receptor opening and weaken neuromuscular transmission. The researchers discovered a previously unknown allosteric binding pocket that can be targeted by positive allosteric modulators (PAMs), compounds that enhance receptor activity without directly activating the channel.
Notably, different PAMs restored receptor function in different patient mutations rather than producing a universal effect. The authors write that this “mutation-specific activity underscores the capability and necessity of tailoring therapies to individual patient genotypes.”
The study also showed that the newly identified drug-binding pocket is largely absent until a PAM binds, creating an opportunity to design more effective compounds that stabilize receptor function. The authors conclude that these findings point to “a new class of allosteric drugs” with potential applications not only in fast-channel CMS but also in disorders such as myasthenia gravis, in which acetylcholine receptor function is compromised.
The team also investigated slow-channel CMS, a gain-of-function disorder in which receptors remain open too long, causing excessive calcium influx and progressive damage at the neuromuscular junction.
Structural analyses revealed that the current therapies quinidine and fluoxetine act through a shared mechanism, blocking the receptor pore despite their distinct chemical structures.
The investigators also evaluated reboxetine, an antidepressant already approved in several countries. Unlike the existing drugs, reboxetine selectively inhibited abnormal receptor activity across multiple slow-channel mutations while largely sparing normal receptor function.
The authors believe that reboxetine’s ability to suppress pathological receptor activity, together with its established clinical safety profile, “positions it as a potential candidate for slow-channel CMS therapy,” although they caution that its known adverse effects warrant careful evaluation in future clinical studies.
Beyond identifying therapeutic opportunities, the study establishes unifying principles of CMS pathogenesis. The researchers found that fast-channel mutations weaken the coupling between acetylcholine binding and channel opening, whereas slow-channel mutations stabilize an abnormally widened, desensitized-like pore. These shared structural mechanisms explain why genetically diverse mutations produce similar clinical symptoms while requiring different therapeutic strategies.
The work also revises understanding of receptor biology. The authors write that their findings “overturn the traditional view of the β subunit as merely a structural scaffold,” instead demonstrating that it plays “a central role in the gating cycle.”
Overall, the researchers conclude that their integrated structural and functional analyses define how CMS mutations disrupt receptor gating, reveal the molecular basis of current and candidate therapies, and identify new druggable sites for intervention. They conclude that the work provides “a roadmap towards the development of safer and more effective, mutation-specific treatments for both fast-channel and slow-channel CMS.”
The post Structural Biology Reveals New Drug Targets for Rare Neuromuscular Disease appeared first on Inside Precision Medicine.
Genetically engineered CAR T cells expressing artificial receptor proteins are increasingly used in the clinic to boost the immune system’s response against leukemias and other cancers. Researchers at Lausanne University Hospital and University of Lausanne, and at Center for Human Immunology Lausanne, have now adapted this approach to suppress the immune system’s response to a common birch pollen allergen. The investigators developed regulatory T cells (Tregs) armed with chimeric allergen receptors (CAlleR Tregs), which in tests reduced or preventing asthma symptoms in mice sensitized to the allergen. The team suggests that their technique could eventually be used to treat a wide variety of allergies in humans.
“Our study provides proof-of-concept and preclinical evidence that CAlleR Tregs redirected against a birch pollen allergen can downmodulate birch pollen–induced allergic asthma,” said study lead Yannick D. Muller, MD, PhD, an associate professor at Lausanne University Hospital and the University of Lausanne.
Muller and colleagues reported on their study in Journal of Experimental Medicine (JEM) in a paper titled “Chimeric allergen receptor regulatory T cells suppress birch pollen allergic airway inflammation,” concluding “These findings unveil a novel mechanism for targeting soluble antigens and highlight the potential of CAlleR Tregs to prevent and treat severe allergies.”
Asthma affects over 300 million people worldwide, around 60% of whom suffer from allergic asthma. Allergens trigger an immune response in a patient’s airways, causing inflammation, excessive mucus production, and difficulty in breathing. “Allergic asthma is driven by an exacerbated type 2 immune response, characterized by the overproduction of IL-4, IL-5, and IL-13 by Th2 cells,” the authors explained. These cytokines trigger events that ultimately result in airway hyperresponsiveness, and airway mucus plugging, which is the primary cause of death in asthma.
Allergen immunotherapy (AIT), which involves the administration of gradually increasing doses of allergen, is the only treatment that addresses the underlying cause of asthma. Yet, it is not recommended for patients with severe asthma, representing the most vulnerable population at greatest risk of asthma-related morbidities and mortality. “This highlights the need for new, safe, and durable treatments for restoring allergen tolerance in severe allergic asthma,” Muller commented.
Regulatory T cells (Tregs) are immune cells that can dampen the body’s immune responses and prevent excessive inflammation. Tregs are being investigated as potential therapies for a variety of inflammatory and autoimmune disorders. “Importantly, Tregs can be expanded ex vivo and reinfused with multiple clinical trials evaluating their potential in autoimmune and inflammatory disorders,” the team continued. “However, Treg therapy has shown only limited efficacy, which has been mostly attributed to the lack of antigen specificity.”
Muller and colleagues wondered whether they could boost the therapeutic potential of Tregs by genetically engineering them to express receptor proteins that recognize specific allergens. This approach is analogous to the CAR T cell method that is now commonly used to treat cancers: cytotoxic T cells are engineered to express chimeric antigen receptors that specifically recognize proteins on the surface of cancer cells, directing the immune system to attack and kill the tumor cells.
A leading cause of allergic asthma is birch tree pollen, to which 8–16% of the European population are sensitive. The birch allergen Bet v1 is the most abundant allergenic protein, the authors commented. And while AIT for birch pollen–associated rhinitis and asthma has been shown to be effective, it is contraindicated for patients with severe and uncontrolled asthma. “This highlights the unmet need for new, safe, and durable treatments for restoring allergen tolerance in severe allergic asthma.”
Muller’s team constructed chimeric allergen receptors (CAlleRs) that specifically recognize the Bev v1 component of birch tree pollen. These CAlleRs were based on antibodies isolated from a birch-allergic patient, linked to protein signaling domains that can activate Treg cells. “We identified and characterized four novel anti–birch-specific antibodies and generated single-chain variable fragments (scFvs) fused to a CD28-ζ signaling domain,” the investigators noted.
Exposure to the birch pollen allergen, when stabilized by noncompetitive antibodies, boosted the suppressive activity of Tregs expressing these CAlleRs. The researchers found that simultaneous binding by a CAlleR and a non-competing antibody promotes receptor–allergen cross-linking underlying a novel mechanism to induce T cell activation by soluble antigens. “This mechanism opens new avenues not only for rewiring synthetic receptors against any soluble antigens including autoantigens for therapeutic intervention but also for delineating a more global pathway for antigen cross-presentation in allergies.”
Muller and colleagues injected these CAlleR-expressing Tregs into mice that were already allergic to birch pollen. When these treated animals were re-exposed to birch pollen, they showed decreased signs of allergic inflammation, reduced mucus production, and increased lung function. Next, the researchers injected CAlleR-expressing Tregs into mice that had never been exposed to birch pollen. When these animals were subsequently exposed to pollen, they failed to develop any asthma symptoms.
The team concluded, “These findings unveil a novel mechanism for targeting soluble antigens and highlight the potential of CAlleR Tregs to prevent and treat severe allergies.” Muller added, “Future studies should evaluate the persistence and stability of CAlleR Tregs over time and define the optimal modalities for implementing such a therapeutic approach.” CAlleRs could also be developed that specifically suppress the immune response to other common allergens, including house dust mites or certain food allergens.” Future work should evaluate whether such approach could also be suitable to restore tolerance against food allergies,” the investigators said.
The post Chimeric Allergen Receptor Treg Cells Suppress Allergic Asthma in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.
Nature Medicine, Published online: 06 July 2026; doi:10.1038/s41591-026-04506-3
Data rights are the missing pillar for modernizing consent in medicine
Nature Medicine, Published online: 06 July 2026; doi:10.1038/s41591-026-04551-y
Author Correction: Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial
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Hope you got to relax this weekend. Here’s my favorite July Fourth video. (It’s loud.)