Blocking Erythropoietin Signaling in Mice Converts Liver Tumors into Immunotherapy Responders

Stanford University scientists have found that erythropoietin (EPO), a protein identified nearly 40 years ago for its ability to stimulate the production of red blood cells also plays a surprising, critical role in dampening the immune system’s response to cancer. Their preclinical studies found that blocking activity of EPO converts formerly “cold” – or immune-resistant – liver tumors in mice into “hot” tumors teeming with cancer-fighting immune cells.

Combining EPO inhibition with an immunotherapy that further activates these immune cells against the cancer led to complete regression of existing liver tumors in the majority of treated mice, which lived for the duration of the experiment. In contrast, control animals survived only a few weeks. Although the work was carried out in preclinical models, there are strong indications that the protein, erythropoietin or EPO, plays a similar role in many types of human cancers.

“This is a fundamental breakthrough in our understanding of how the immune system is turned off and on in cancer,” said Edgar Engleman, MD, PhD, a Stanford University professor of pathology and of medicine. “I could not be more excited about this discovery, and I hope treatments that target the mechanism we uncovered will quickly move forward to human trials.”

Senior author Engleman, together with first author research scientist David Kung-Chun Chiu, PhD, and colleagues, reported on their findings in Science, in a paper titled “Tumor-derived erythropoietin acts as an immunosuppressive switch in cancer immunity.”

Successful cancer immunotherapy requires a patient to mount an effective immune response against tumors, but many cancers evade the body’s immune system, the authors explained.

For their reported study the team set out to investigate factors that govern antitumor immunity and tumor immunotype. Interestingly, the team noted, “EPO, a glycoprotein hormone known for stimulating red blood cell production, has recently been implicated in other biological processes involving resolution of inflammation.” Engleman added, “Research from more than a decade ago has shown that giving EPO to cancer patients with anemia to stimulate red blood cell formation accelerates the growth of the tumor.”

The connection was so striking that in 2007 FDA required a black box warning label on the drug cautioning against its use in people with cancers. Researchers also saw a clear correlation between patient prognosis and the levels of naturally occurring EPO and its receptor (EPOR) in the tumor. “Clinically, high expression of EPO is linked to poor prognosis in several cancers, including HCC, and accumulation of immunosuppressive cells such as regulatory T cells (Treg cells) and regulatory macrophages,” the team stated in their paper.

“Those old reports showed clearly that the more EPO or EPOR there was in tumors, the worse off the patients were,” Engleman said. “But the connection between EPO and cancer immunity was never made until now. In fact, it took a long time and a lot of experiments to convince us that EPO plays a fundamental role in blocking the immune response to cancer, because EPO is so well established as a red blood cell growth factor.”

The researchers were interested in the effect on cancer growth of a common immunotherapy targeting a molecule called PD-1 on immune cells called T cells. Binding to PD-1 blocks the ability of cancer cells to dampen the activity of T cells. Anti-PD-1 therapies are routinely used to treat many types of human cancers including melanoma, Hodgkin’s lymphoma and some types of lung cancer. In some cases they have transformed patient outcomes. But a large majority of tumors, including most liver, pancreas, colon, breast and prostate cancers are resistant to the treatment.

“Cancer patients with inflamed (T cell–rich) tumors, indicative of an active antitumor immune response, often benefit from immune checkpoint blockade (ICB) therapy,” the team noted in their research article summary. “However, despite the presence of tumor mutations that should theoretically trigger an immune response, most patients have noninflamed (T cell–deprived) tumors and do not benefit from ICB … the mechanisms that determine the immune cell profile or immunotype of tumors remain poorly understood.”

The researchers further pointed out that such noninflamed tumors are often “ … replete with immunosuppressive macrophages and neutrophils that hinder T cell priming, activation, and homing—critical processes for fostering antitumor immunity.”

Using somatic genome editing techniques the investigators created and compared several mouse models of liver cancer to help study how liver tumors develop and respond to treatment. “To investigate the basis for treatment failure, we examined spontaneous mouse models of hepatocellular carcinoma (HCC) with either an inflamed T cell–rich or a noninflamed T cell–deprived tumor microenvironment (TME),” the researchers explained in their paper. Each model recapitulates specific mutations, histology and the response to approved therapies found in subtypes of human liver cancers. Tumor formation was either induced by injecting a combination of DNA encoding proteins associated with liver cancer into the animals’ tail vein or by implanting liver cancer cells into the animals’ livers.

The researchers found that, similar to what has been observed in human liver cancers, some combinations of mutations led to the development of liver tumors that were largely ignored by the immune system, rendering them immune privileged, or cold. These tumors did not shrink when the animals were treated with anti-PD-1 because few T cells were present in the tumor.

In contrast to the cold tumors, other mutations led to hot or “inflamed” tumors that were replete with T cells. These tumors were highly sensitive to anti-PD1 treatment, which triggered the T cells to attack the cancer.

Unexpectedly, the cold tumors displayed elevated levels of EPO when compared with hot tumors. This increase is likely caused by the oxygen-poor microenvironment—a condition called hypoxia—prevalent in cold tumors. Hypoxia induces the production of proteins in cancer cells that, in turn, ramp up the production of EPO to create more red blood cells to combat low oxygen levels. “Hypoxia in tumors has been studied for decades,” Engleman said. “It just didn’t dawn on anyone, including me, that EPO could be doing anything in this context other than serving as a red blood cell growth factor.”

In their research article summary, the authors noted, “Using spontaneous preclinical models of HCC with distinct immunotypes, we show that the EPO/EPOR axis functions as an immunosuppressive switch in macrophages that maintains a T cell–deprived TME, thus posing a major barrier to effective antitumor immunity.”

The researchers also turned to existing databases to confirm that elevated levels of EPO are correlated with poorer survival of people with cancers of the liver, kidney, breast, colon and skin. They then tinkered with the ability of the tumor cells to make EPO and were surprised at what happened in the animals’ liver tumors.

They found that mutations that had led to the development of cold tumors instead caused hot tumors when the tumors were modified to be unable to make EPO. Conversely, hot tumors that had previously been successfully eradicated by the immune system thrived when they were engineered to make elevated levels of EPO.

Further exhaustive research showed that, in cold tumors, the tumor cells make and secrete EPO, which binds to receptors on the surface of immune cells called macrophages. “Tumor-derived EPO autonomously generates a noninflamed TME by interacting with its cognate receptor EPOR on tumor associated macrophages (TAMs),” the authors stated. The macrophages then switch to an immunosuppressive role, shooing away cancer-killing T cells and tamping down their activity. “Collectively, our data strongly support the notion that noninflamed HCC relies on EPO production to evade immune surveillance, with the macrophage EPO/EPOR axis being the primary immunosuppressive mechanism,” they added.

The importance of this EPO-moderated crosstalk between tumor cells and macrophages showed clearly when the researchers studied the combinatorial effect of simultaneously blocking the EPO signaling pathway and anti-PD-1 pathway.

In those experiments, no mice with cold liver tumors that were treated with control or with anti-PD-1 lived more than eight weeks after tumor induction. In contrast, 40% of mice with macrophages unable to make the EPO receptor lived for 18 weeks after tumor induction, the point at which the experiment was terminated. When anti-PD-1 treatment was given to mice lacking the EPO receptor, all animals lived for the duration of the experiment. “Removing either tumor-derived EPO or EPOR on TAMs leads to an inflamed TME and tumor regression independent of genotype,” the authors further pointed out. “Inactivation of EPO/EPOR reprograms macrophages to initiate a robust antitumor immune response, converting a noninflamed TME into an inflamed one.”

Added Engleman, “It’s simple. If you remove this EPO signaling, either by lowering the hormone levels or by blocking the receptors on the macrophages, you don’t just get a reduction in tumor growth, you get tumor regression along with sensitivity to anti-PD-1treatment.”

Engleman and his colleagues are now designing treatments targeting EPO signaling in human cancers. Non-specifically targeting the EPO protein could cause anemia, which Engleman speculates might be an acceptable trade-off for an effective cancer therapy. An alternative approach is to selectively block the EPO receptors on the surfaces of macrophages in the cancer. “I continue to be amazed by this finding,” Engleman said. “Not every tumor is going to respond in the same way, but I’m very optimistic that this discovery will lead to powerful new cancer therapies.”

The authors acknowledged that their study relied on murine models of HCC, which limits generalization, although they noted that “… the association between high EPO expression and poor prognosis across various solid malignancies suggests that similar mechanisms could contribute to the noninflamed immunotype and resistance to anti–PD-1 immunotherapy in other tumor types. On this basis, targeting the EPO/EPOR axis may have application for the treatment of solid tumors beyond HCC.”

Sugar Swap Leads to Sweet Spot in Creating “Super Stem Cells”

A small shift in nutrient supply has led to the development of a new method to rejuvenate stem cells. Scientists at the University of Copenhagen found that these “super stem cells” remain healthier in culture and demonstrate an improved ability to differentiate into various specialized cell types. This small but impactful change to stem cell culture could advance both fertility treatment and regenerative medicine.

Led by Robert Bone, PhD, assistant professor at the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), the research team identified that a small modification to the standard stem cell culture media—replacing glucose with galactose—resulted in the cells switching their primary energy source from glycolysis to oxidative phosphorylation.

“We show that by changing their diet, the stem cells can rejuvenate and turn into ‘super stem cells’,” said Bone. “It forces them to metabolize their energy in a different way than they normally would, and that process essentially reprograms the stem cells.”

Their study was published in The EMBO Journal under the title, “Altering metabolism programs cell identity via NAD+-dependent deacetylation.”

Using embryonic stem cells (ESCs) from mice, the team replaced glucose with galactose in culture media. By changing their nutrient source, the ESCs are reprogrammed into an earlier stage of development, more similar to the inner cell mass (ICM) of the early mammalian blastocyst.

“The net result is that they behave like they are from an earlier stage of development, which enhances their ability to develop, or differentiate, into other types of cells,” said Bone.

The reprogramming of these cells activates NAD⁺-dependent sirtuin deacetylases—enzymes that play a central role in regulating aging and gene expression—resulting in deacetylation of histone and key transcription factors that enhance their identity and function.

Transcriptional noise is also reduced, as the chromatin is more densely packed in areas with redundant or irrelevant genetic information and more accessible in areas encoding developmental instructions.

“What’s really striking is that they’re not just better at differentiating, but they stay fit and keep healthy much better over time compared to stem cells in standard culture conditions,” said senior author Joshua Brickman, PhD, professor at reNEW. “And it is done with a relatively simple method.”

IVF and regenerative applications

Among the most immediate translational prospects is in vitro fertilization (IVF). The researchers observed that their metabolically reprogrammed stem cells had enhanced capacity to form extraembryonic tissue.

“One of the things that the ‘super stem cells’ seem to be better at making is a cell lineage that becomes something called the yolk sac,” said Bone. “Previous research has found that the formation of the yolk sac in embryos cultured in a dish is very important for their ability to implant and become successful pregnancies.”

The team looks forward to the use of this strategy in clinical applications. “We hope to improve IVF technology by developing a culture for IVF that uses the same metabolic process,” added Brickman. “Hopefully, it can be used as part of the embryo culture regime that they use in the clinic to improve success rates of implantation.”

Additionally, this study has broader implications on aging and age-related disease studies. As they are more similar to ICMs, the rejuvenated ESCs may generate tissues such as liver, skin, and neural lineages in culture more efficiently. The implications span a wide range of therapeutic applications, from tissue regeneration to neurodegenerative disease. The team aims to further study the possibility of using this strategy on other cell types.

“Perhaps we could use this trick to regenerate aging cells and treat diseases such as Parkinson’s disease, osteoporosis, or diabetes,” supposed Brickman. “Can we use this diet to revitalize liver or heart cells and use them to treat patients with congestive heart failure or liver cirrhosis?”

The study provides fresh insight into how environmental changes—such as nutrient availability—can influence cellular identity and fate. The findings lay important groundwork for developing robust and therapeutically useful stem cell populations through metabolic reprogramming.

Plant-based calamari rivals real seafood in texture

Plant-based seafood alternatives should have similar flavors, textures and nutritional content to the foods they mimic. And recreating the properties of fried calamari rings, which have a neutral flavor and a firm, chewy texture after being cooked, has been a challenge.

Building off previous research, a team publishing in ACS Food Science & Technology describes successfully using plant-based ingredients to mimic calamari that matches the real seafood’s characteristic softness and elasticity.

Previously, Poornima Vijayan, Dejian Huang and colleagues presented air-fried vegan calamari rings made from a 3D-printed paste of microalgae and mung bean proteins at ACS Fall 2023, a meeting of the American Chemical Society. When the researchers air-fried the calamari mimic (demonstrated in the short video below), it had an acceptable taste, but they noted that the texture wasn’t ideal.

So, now they’ve optimized the recipe and printing parameters, improving the plant-based product’s texture so that it’s more like real calamari when battered and deep-fried—the way most calamari is prepared.

The researchers tested multiple versions of their printable paste recipe, varying the amounts of mung bean protein isolate, powdered light-yellow microalgae, gellan gum (thickener) and canola oil (fat). A food-grade 3D printer deposited the pastes into layered rings about 1.8 inches wide (4.5 centimeters). Unlike the original research, this time the researchers froze the rings overnight and then battered and quickly deep-fried them.

In lab tests, the researchers analyzed properties related to the cooked samples’ chewiness, including hardness, springiness and cohesiveness. The deep-fried product with the textural properties closest to real calamari contained 1.5% gellan gum, 2% canola oil and 10% powdered microalgae.

From microscope images, the researchers saw that small voids in the structure of these plant-based samples modified their softness, so they resembled the real seafood counterpart. Additionally, an analysis of the protein content in the optimal recipe found that the plant-based version could have more protein (19%) than the reported protein composition of squid (14%).

“This research showcases the potential of 3D printing to transform sustainable plant proteins like mung bean and microalgae into seafood analogs with comparable texture,” says Vijayan, the study’s lead author. “Our next steps involve understanding consumer acceptance and scaling formulation for broader applications.”

Prairie grass shows benefits for sustainable aviation fuel in studies

Switchgrass has gripped Midwestern soils for millions of years, but soon, the earthbound prairie grass could fly. New studies from the University of Illinois Urbana-Champaign identify economic and environmental considerations that make switchgrass a candidate for sustainable aviation fuel.

The Sustainable Aviation Fuel Grand Challenge kicked off in 2021 with the goal of expanding SAF production to 35 billion gallons by 2050, while cutting greenhouse gas emissions in half. Forecasted to contribute up to 230 million dry tons annually, switchgrass is one of several purpose-grown bioenergy feedstocks that could help meet this challenge. Not only does the perennial species produce great quantities of biomass, switchgrass can be harvested annually for a decade or more without repeated planting, requires minimal nitrogen fertilizer compared to corn, and performs important ecosystem services.

Scientists know this because they have been studying switchgrass for its bioenergy potential for decades. But previous studies used less productive switchgrass cultivars, were conducted on smaller and less realistic plots of land, or overlooked the fertilizer inputs required for optimal productivity. In two new studies, U. of I. researchers grew modern “energy” cultivars at the field scale across the Midwest to determine which cultivars are most profitable where, and how they compare to corn in terms of ecosystem services.

“All the data that helps us estimate switchgrass suitability for SAF comes from small plot research or older forage-type switchgrass cultivars. We wanted to test high-yielding switchgrass cultivars on a larger scale to provide a more accurate picture of the benefits these new cultivars provide,” said D.K. Lee, senior author of both studies and professor in the Department of Crop Sciences, part of the College of Agricultural, Consumer and Environmental Sciences at U. of I.

Postdoctoral researcher Muhammad Umer Arshad led the effort to analyze switchgrass profitability. The team planted three newer energy-type cultivars—Independence, Liberty, and Carthage—alongside two forage cultivars—Shawnee and Sunburst—on low-productivity marginal land across four Midwestern states: Illinois, Iowa, Nebraska, and South Dakota. They also tested two nitrogen fertilizer rates, 28 and 56 kilograms per hectare; for comparison, corn typically gets about 200. After five years of growth, Arshad conducted economic analyses to calculate expenses and profits in each location.

“Our findings clearly show that Independence and Liberty are much more profitable than the forage cultivars on all the sites, but the most profitable nitrogen rate varied across locations,” Arshad said. “In most cases, 56 kilograms per hectare achieved higher yields, but in some sites, 28 kilograms performed better in terms of profit.”

Although Independence and Liberty outperformed the forage cultivars, these energy types of switchgrass did not perform equally across the sites. For example, depending on the nitrogen rate, Independence was most profitable in U.S. hardiness zone 6a, whereas Liberty showed the highest profit margins in zone 5b and Carthage, was most profitable in zone 4b.

“With these energy-type cultivars, farmers can put marginal lands to use and see returns after two years,” Arshad said. “Our results can help guide decision-makers to optimize input strategies for biomass production and meet renewable energy demands.”

During the decade or so that switchgrass is churning out biomass, it’s also busy providing ecosystem services—a win-win, according to postdoctoral fellow Nictor Namoi, who led a companion study in field-scale plots in Illinois.

Namoi assessed soil greenhouse gas emissions (carbon dioxide and nitrous oxide) and nitrate leaching in Independence switchgrass over three years, and compared these metrics to other fields planted in continuous corn under no-till management. The idea was to compare ecosystem services for these two cropping systems on equal footing.

“One of the many benefits of growing purpose-grown energy crops on marginal lands is ecosystem services associated with the perennial nature of energy crops. They can also potentially generate higher profits than conventional row crops on less productive land,” Namoi said. “Demonstrating ecosystem services of switchgrass, including reduction of greenhouse gas emissions and nutrient loss, will promote purpose-grown energy crops on marginal land.”

Nitrous oxide emissions and nitrate leaching were significantly reduced in switchgrass compared to corn, with 80% less nitrate leaching by the third year. Namoi says the nitrous oxide finding is straightforward: with switchgrass getting just 56 kilograms of nitrogen fertilizer per hectare and corn receiving 202 kilograms, there’s a lot more nitrogen available in corn fields to be emitted as the potent greenhouse gas.

Carbon dioxide emissions were less straightforward. After the second year, CO2 emissions were over 50% higher in switchgrass than in corn.

“I wasn’t expecting that,” Namoi said. “But there’s a lot more biomass belowground in switchgrass, about five times that of corn.”

More roots mean more respiration, the normal process in which roots convert oxygen and glucose into energy, with carbon dioxide as a byproduct. Lee says he’s seen this pattern with switchgrass and other purpose-grown bioenergy crops before, but he’s still convinced that the overall benefits of switchgrass outweigh this particular deficit.

“For one thing, more root biomass means more long-term carbon sequestration potential,” he said. “When we measure total biomass of switchgrass, there’s about 10 megagrams of carbon belowground. That’s huge.”

Another key advantage of switchgrass, Namoi added, is its ability to thrive on marginal land.

“By definition, marginal land is not profitable for commodity crops,” he said. “So switchgrass reduces competition with food crops and makes use of otherwise unproductive areas.”

With commodity and oil prices at a low point, the demand for purpose-grown bioenergy feedstocks is relatively weak at the moment. But that could all change rapidly as tariffs impact global economies. Namoi says when the market is ready, switchgrass will be, too.

“Our research ensures that we can feed productive cultivars into the SAF production system once the economy and the technology is ready to transition,” he said.

The first study, “Comparative Economic Analysis Between Bioenergy and Forage Types of Switchgrass for Sustainable Biofuel Feedstock Production: A Data Envelopment Analysis and Cost–Benefit Analysis Approach,” is published in GCB Bioenergy.

The second study, “Field-Scale Evaluation of Ecosystem Service Benefits of Bioenergy Switchgrass,” is published in the Journal of Environmental Quality.

Psychedelics May Reverse Effects of Neuroimmune Interactions That Drive Fear Responses

A newly reported study suggests that fear and the immune system are connected in previously unknown ways. Results from the preclinical research, headed by scientists at Mass General Brigham, showed that interactions between immune and brain cells drive fear responses, and suggest that treatment with psychedelics such as 3,4-methylenedioxymethamphetamine (MDMA), or psilocybin, may reverse these effects.

Collective findings from the study, including work in mouse models and in human tissues, indicated that the immune system can influence stress and fear behaviors by changing how brain cells communicate. Headed by Michael Wheeler, PhD, at the Gene Lay Institute of Immunology and Inflammation, and the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital, the investigators further showed that psychedelic treatments could target these neuroimmune interactions and reduce stress-induced fear in preclinical models. They found similar results in human tissue samples.

“Our study underscores how psychedelics can do more than just change perception; they can help dial down inflammation and reset brain-immune interactions,” said Wheeler. “This could reshape how we think about treatment for inflammatory disorders and conditions like anxiety and depression.” Wheeler is corresponding author of the team’s published paper in Nature, titled “Psychedelic control of neuroimmune interactions governing fear,” in which the researchers stated, “Together with validation in clinical samples, these data suggest that psychedelics can be used to target neuroimmune interactions relevant to neuropsychiatric disorders and potentially other inflammatory diseases.”

Prior research has shown immune signaling can drive the development of neuropsychiatric diseases such as major depressive disorder, the authors wrote. “Neuroimmune interactions—signals transmitted between immune and brain cells—regulate many aspects of tissue physiology, including responses to psychological stress, which can predispose individuals to develop neuropsychiatric diseases.” However, the team further stated that the ways specific immune mechanisms can also affect behaviors due to chronic stress or MDD remained unclear. “… although immunotherapies that target peripheral signals induced by psychological stress may be a viable therapeutic area in neuropsychiatric disorders such as MDD,” the team continued, “many relationships between behavioral changes and immunoregulatory mechanisms in the brain remain to be defined.”

For their reported study, the team studied a mouse model of chronic stress. Results from initial tests with the animals showed that in response to chronic stress, plasma levels of corticosterone and certain cytokines and a chemokine were increased. “These results implicate potential links among chronic stress, peripheral inflammatory responses, fear behavior, and neuroimmune interactions,” they reported. Subsequent studies found that increased crosstalk between cells in the amygdala, or the brain’s fear center, boosted fear behaviors, elevated inflammatory signaling, and activated fear-promoting amygdala neurons.

Furthermore, their research showed that inflammatory immune cells called monocytes migrated from other parts of the body to the brain meninges during chronic stress. The research team demonstrated that artificially manipulating these cells impacted fear behaviors. “… we use a combination of genomic and behavioural screens to show that astrocytes in the amygdala limit stress-induced fear behavior through epidermal growth factor receptor (EGFR),” they explained. “… we uncovered a psychedelic-sensitive neuroimmune signaling axis tuned by the recruitment of inflammatory monocytes to the brain meninges, which influences astrocyte–neuron responses in the amygdala and fear behavior.”

The investigators also reported that treating stressed mice with psilocybin and MDMA prevented monocytes from accumulating in the brain and lowered fear behaviors. “By using a phenotypic screen of shared properties among two clinically relevant psychedelics, analogous to studies of social behavior, we found that both psilocybin and MDMA similarly influence immune-cell abundance in tissues,” the authors stated. The resulting data, the scientists continued, “… point to potential direct and indirect mechanisms by which psychedelics influence physiological responses to chronic stress and neuroimmune interactions.”

The investigators found similar signals of response to stress in human brain cells and in gene expression datasets from patients with MDD, suggesting that the same interactions between the immune system and the brain may play a role in neuropsychiatric disorders in humans. These results, they reported, “… suggest that the neuroimmune mechanisms we initially defined in mice may be relevant in humans and in MDD.”

The authors noted that further experiments are needed to understand exactly how psychedelics affect immune cells and brain communication. “Further research is needed to establish causal cellular and molecular mechanisms by which psychedelics influence tissue physiology more generally, which may reveal psychedelic-responsive pathways with therapeutic applications in unanticipated disorders, including in inflammatory diseases,” they stated. Next steps include examining the long-term effects of psychedelic treatment on patients with MDD or inflammatory diseases. Wheeler is currently collaborating with investigators from the Massachusetts General Hospital Center for the Neuroscience of Psychedelics on a clinical trial of patients with depression who are being treated with psychedelics and will examine their tissue samples.

“We’re not saying that psychedelics are a cure-all for inflammatory diseases or any other health condition,” said Wheeler. “But we do see evidence that psychedelics have some tissue-specific benefits and that learning more about them could open up entirely new possibilities for treatments.”

In their report, the team concluded, “This study defined mechanisms of astrocyte–neuron crosstalk in the amygdala and their potential regulation by peripheral immune cells in chronic stress and possibly MDD. Together, our results highlight the therapeutic potential of targeting immune mechanisms in neuropsychiatric disorders.”

Watchmaker Genomics and Revvity Team to Automate and Streamline NGS Library Preparation

Watchmaker Genomics says it will collaborate with Revvity to automate and verify methods for all of its DNA and RNA library preparation kits on the Sciclone™ G3 NGSx liquid handling workstation. The agreement makes Revvity the first provider to automate Watchmaker’s entire library preparation portfolio.

By integrating Watchmaker’s streamlined DNA and RNA library preparation kits with Revvity’s platform, laboratories can now implement automation with optimized, ready-to-run protocols that reduce hands-on time, reduce errors, and increase throughput, according to Sandra Rowe, vp of marketing at Watchmaker Genomics. The collaboration delivers end-to-end automation of Watchmaker’s NGS library preparation portfolio, including support for low-input and FFPE sample types, and enables up to 96 samples per run, she added.

“As we launch new innovations such as TAPS for methylation analysis and library normalization tools, continued collaboration with Revvity will be key to ensuring these technologies are accessible and scalable,” said Rowe.

“We’re teaming up with Watchmaker to deliver robust, automated workflows that help genomics labs simplify operations and improve data quality,” said Kevin Quick, vp of platforms at Revvity. “We look forward to continuing this collaboration, including extending method availability to additional platforms to bring even more flexible and scalable NGS solutions to researchers worldwide.”

The Sciclone G3 NGSx platform is a high-throughput liquid handling system used in genomic labs for library prep, PCR setup, and sample processing. Coupled with Watchmaker’s library prep kits, labs can now run entire workflows more efficiently, said Quick.

EditCo, Promega to Combine CRISPR Knock-In Capabilities with Protein-Labeling Tech

EditCo Bio and Promega have announced a strategic licensing agreement that grants EditCo access to Promega’s HiBiT, HaloTag, and NanoLuc technologies. Under the terms of the arrangement, EditCo will incorporate Promega’s bioluminescent and protein-labeling technologies into its CRISPR-engineered cell lines. According to the partners, the combined solutions will allow customers to generate precise gene edits in cell lines with functional validation.

Promega’s HiBiT technology is a small bioluminescent peptide tag for quantitative analysis of protein expression and interactions in live cells. The HaloTag is a protein labeling system that relies on covalently attaching fluorescent and bioluminescent probes for use in imaging, protein interaction studies, and biochemical assays. Finally, the NanoLuc technology is a luciferase enzyme that provides a bioluminescent signal for monitoring cellular and molecular processes in real-time.

Through this agreement, EditCo will be able to facilitate precise genomic knock-ins and also offer functional validation services that ensure that engineered cells maintain proper protein expression, stability, and activity. Cell models produced from the combined capabilities could be used for mechanistic studies, drug screening, and other advanced applications that require quantitative protein analysis.

Integrating HiBiT, HaloTag, and NanoLuc into EditCo’s knock-in workflows provides researchers with “powerful tools to track protein expression, interactions, and activity with high sensitivity and accuracy,” said Travis Maures, PhD, CSO at EditCo Bio. Specifically, scientists will be able to “probe protein dynamics directly within living cells, empowering deeper insights into complex biological mechanisms,” added Tom Livelli, Promega’s vice president for life sciences.

Earlier this year, EditCo launched XDel Knockout Cells, a new CRISPR-based gene editing product that uses up to three guideRNAs to create fragment deletions in target genes.

At the time of the launch, Maures explained to GEN that the guides work cooperatively, meaning that as each individual one binds, it unwinds the DNA in a way that makes it easier for the next one to bind. The result is a “product where the knockout percent is in the high 90s,” he said. Furthermore, because it’s so efficient, “we can titrate down the dose that the cells get of guides and CRISPR complexes,” which reduces the risks of off-target effects, he added. “That’s also part of the optimization of our process.”

The product is available in a variety of customizable formats, including cell pools, cell clones, and engineered cell libraries. Researchers can select from immortalized cells or induced pluripotent stem cells, either customer-supplied or EditCo-supplied.

Electricity-conducting organism named after Native American Tribe may advance bioelectronic devices

Scientists have identified a novel species of bacteria that acts as electrical wiring, potentially ushering in a new era of bioelectronic devices for use in medicine, industry, food safety, and environmental monitoring and cleanup.

The researchers who discovered the new cable bacteria species in a mud flat at the Oregon coast named it Ca. Electrothrix yaqonensis in honor of the Native Americans of the region where the species was found.

The findings are published in Applied and Environmental Microbiology.

Cheng Li, a postdoctoral researcher at Oregon State University at the time of the research, and Clare Reimers, distinguished professor emerita in the OSU College of Earth, Ocean, and Atmospheric Sciences, identified the new species in intertidal sediment samples from the Yaquina Bay estuary.

Cable bacteria consist of rod-shaped cells attached end to end with a shared outer membrane, forming filaments that can reach several centimeters in length. Their electrical conductivity, unusual among bacteria, is an adaptation that optimizes their metabolic processes in the sediment environments in which they live.

The new species features metabolic pathways and genes that are a mix of the Ca. Electrothrix genus and the other known cable bacteria genus, Ca. Electronema.

“This new species seems to be a bridge, an early branch within the Ca. Electrothrix clade, which suggests it could provide new insights into how these bacteria evolved and how they might function in different environments,” said Li, who in June will return to Oregon State as an assistant professor in the College of Agricultural Sciences following a stint on the faculty of James Madison University.

“It stands out from all other described cable bacteria species in terms of its metabolic potential, and it has distinctive structural features, including pronounced surface ridges, up to three times wider than those seen in other species, that house highly conductive fibers made of unique, nickel-based molecules.”

The fibers enable the bacteria to perform long-distance electron transport, connecting electron acceptors like oxygen or nitrate at the sediment surface with donors like sulfide in deeper sediment layers. The bacteria’s ability to participate in reduction-oxidation reactions over significant distances gives it a key role in sediment geochemistry and nutrient cycling.

“These bacteria can transfer electrons to clean up pollutants, so they could be used to remove harmful substances from sediments,” Li said. “Also, their design of a highly conductive nickel protein can possibly inspire new bioelectronics.”

Cable bacteria can live under diverse climatic conditions and are found in various environments, including both freshwater and saltwater sediments.

Ca. Electrothrix yaqonensis draws its name from the Yaqona people, whose ancestral lands encompassed Yaquina Bay. Yaqona referred to the bay and river that made up much of their homeland, as well as to the people themselves.

Today, Yaqona descendants are part of the Confederated Tribes of Siletz Indians, with whom the researchers worked on coming up with a name for the new species.

“Naming an ecologically important bacterium after a Tribe recognizes its historical bond with the land and acknowledges its enduring contributions to ecological knowledge and sustainability,” Li said.

Scientists from the University of Antwerp, Delft University of Technology and the University of Vienna also participated in the research.

California-based Tempest Therapeutics is laying off 21 of its 26 full-time employees. The cuts come while the biotech is exploring strategic alternatives, including a merger or acquisition, as it tries to move its investigational PPARα antagonist into late-stage development.
About a week after announcing it was eyeing strategic alternatives, including a merger or acquisition, Tempest Therapeutics disclosed it is cutting about 80% of its workforce. The Brisbane, California–based biotech is letting go of 21 of its 26 full-time employees effective April 30, according to an April 18 SEC filing. The company expects key staff will transition to consulting agreements.

Tempest expects to incur about $1.5 million in costs in connection with the workforce reduction, primarily in one-time severance payments, according to the filing.

On April 9, the company announced it was exploring strategic alternatives so it could advance clinical-stage programs and maximize stockholder value. Those programs include the PPARα antagonist amezalpat, which has FDA orphan drug and fast track designations for hepatocellular carcinoma (HCC) and which the biotech deemed “Phase 3-ready” in the press release. In addition to a merger or acquisition, Tempest said it was also considering partnerships, licensing deals or joint ventures.

The biotech already has one partner for small-molecule drug amezalpat. In October, Tempest announced an agreement with Roche to study amezalpat in combination with Tecentriq and bevacizumab, which Roche markets under the brand name Avastin, for use in treating unresectable or metastatic HCC.

Tempest had a net loss of $41.8 million and an accumulated deficit of $207.1 million as of Dec. 31, 2024, according to a March 27 SEC filing. The biotech also noted it had cash and cash equivalents of $30.3 million at the end of last year. In a March 27 note to investors, William Blair analysts noted that the $30.3 million was only enough to cover “start-up costs” of a Phase III trial for amezalpat.

Banning Industry From FDA Adcomms Won’t ‘Move the Needle Much’ in Makary, RFK’s Fight Against COIs

FDA Commissioner Marty Makary last week announced a directive that would limit industry participation in the agency’s advisory committees. But not only do company reps serve only as non-voting members, a 1997 law actually requires industry involvement.
Newly confirmed FDA commissioner Marty Makary wants to “restore impeccable integrity” to the drug review process, and he’s starting by banning pharmaceutical representatives from serving as members on some of the agency’s advisory committees. Reaction to this move, however, has been relatively muted.

“I don’t think [the new directive] will move the needle much,” Genevieve Kanter, an associate professor of public policy at the University of Southern California Price School of Public Policy, told BioSpace in an email. Kanter specifically noted that industry representatives are already non-voting members. “The central and perhaps more difficult conflict of interest issues relate to the industry ties of the scientific members of the committee, and that issue hasn’t been directly addressed yet,” Kanter said.

Steven Grossman, policy and regulatory consultant and author of the FDA Matters blog, concurred. “My advice to stakeholders: put your energies into proposals that make more of a difference than this one,” he told BioSpace in an email.

It’s unclear at this point how comprehensive the new policy will be. The new directive “limits individuals employed at companies regulated by the [FDA], such as pharmaceutical companies, from serving as official members on FDA advisory committees, where statutorily allowed,” according to the agency’s Friday announcement.

This reference to “statutorily allowed” could present a bit of a quagmire for the FDA. A provision in the Food and Drug Administration Modernization Act of 1997 “has been interpreted to mean that newly created advisory committees must include an industry representative,” Kanter said. “My guess is that the FDA may remove industry reps from advisory committees that existed prior to 1997.”

As of April 2024, the FDA had 33 advisory committees. The advisory panel, the Obstetrics and Gynecology Advisory Committee, was established in 1965, largely to track the safety of thalidomide. As of 1967, the Anti-Infective Agents Advisory Committee was also up and running. As of 1997, the Vaccines and Related Biological Products Advisory Committee and Oncologic Drugs Advisory Committee were also active.

But for advisory committees established after that 1997 legislation, it seems that industry representatives cannot, by law, be excluded.

Another interpretation is that the language only applies to advisory committees “regarding a clinical investigation or the approval for market for a drug,” Kanter said. Panels that review, for example, post-market safety or that discuss other regulatory issues, would not be required to have an industry rep.

Makary: ‘Surrounded by Swamp Creatures’

The question of potential industry influence on the FDA has been simmering for years, largely centered around the so-called “revolving door,” through which employees move from industry to FDA and vice versa. In an interview with former Fox News journalist Megyn Kelly last week, Makary referenced the case of Curtis Wright, the FDA examiner who signed off on Purdue’s infamous painkiller OxyContin and later left the agency to work for the now-defunct pharma.

“That’s the kind of thing that breeds distrust and that’s why people perceive that this agency, the FDA, has been captured by industry,” Makary told Kelly.

Newly appointed Health and Human Services Commissioner Robert F. Kennedy Jr. has taken this up, along with other potential “conflicts of interest,” he sees within the FDA. In a tour of the FDA campus earlier this month, Kennedy blasted the agency and its staff, accusing them of being a “sock puppet” to the pharma industry. After ousting Peter Marks, head of the FDA’s Center for Biologics Evaluation and Research, the FDA appointed interim director Scott Steele, who has never worked at a biopharma company.

At another point during the interview, Makary said he was “surrounded by the swamp creatures” after his nomination for FDA commissioner.

“When I got his nomination for the job, I cannot tell you how many lobbyists, former members of Congress, the swamp, reached out to me,” offering to write letters on behalf of their companies to the senators on the confirmation committee. “You know what I said? Don’t talk to the senators. I don’t want your letters. They’re not for free. Those are obligations that then you feel indebted to return once you’re in office.”

The Advisory Committee Debate

Addressing the new policy directive regarding adcomms, Makary said, “The idea is that there should not be a cozy relationship. . . . There should be a user-friendly process for industry, but not a cozy relationship.”

For his part, Grossman offered points on both sides. “Industry representatives on advisory panels do not vote, do not have a professional or monetary interest in the outcome and have little ability to sway the outcome. Yet, they do provide a useful perspective that other panelists often value,” he said. “Nonetheless, the appearance is jarring and it is understandable that questions are being raised.”

Kanter added that industry reps “could present a practical perspective on the feasibility and implications of committee recommendations, as well as important constraints facing the sector—for example, issues with the supply chain or manufacturing.” The sponsor, who would also be in the meeting, “isn’t generally able to raise these concerns without being directly asked by committee members.”

As per Thursday’s announcement, Makary plans to replace the ousted industry representatives with input from patients, caregivers and other community representatives.

“Patient advocates and caregivers know a great deal about the health conditions that are affecting their daily lives, and some of them may be physicians or researchers themselves,” Kanter said. She acknowledged, however, that “in general, they do not go through the same screening process for scientific expertise as the other members and may not know as much about the scientific issues.”

Instead, these panel members play a different role in the conversation, “introducing information about the experience of living with the health condition or caring for someone with the condition, the needs, priorities, and sentiment of the patient community at large, and adding context and perhaps helping interpret the numbers and statistics,” Kanter continued.

Overall, she said, “This move is an important sign that Commissioner Makary will take a second look at the issue of industry influence on FDA activities, and I am generally supportive of that.”

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