Two months after saying it was in advanced talks to acquire SpringWorks Therapeutics, Merck KGaA, Darmstadt, Germany, has announced it agreed to purchase the developer of drugs for severe rare disease and cancer for $3.9 billion.

Merck KGaA said the deal will grow its U.S. presence and expand the reach of SpringWorks’ drugs, including one approved in February.

More pointedly, Merck KGaA signaled that its purchase of SpringWorks could be the first of several potential merger-and-acquisition (M&A) deals by the healthcare, life science, and electronics giant.

“Beyond this planned transaction, we will continue to explore M&A opportunities across our three complementary business sectors, always with a firm focus on strategic fit, financial robustness, and long-term value creation,” Belén Garijo, chair of the executive board and CEO of Merck KGaA, Darmstadt, Germany, said Monday in a statement.

“The agreed acquisition of SpringWorks is a major step in our active portfolio strategy to position Merck KGaA, Darmstadt, Germany as a globally diversified, innovation and technology powerhouse,” Garijo added. “For our Healthcare sector, it sharpens the focus on rare tumors, accelerates growth, and strengthens our presence in the United States.”

SpringWorks complements Merck KGaA’s recent oncology focus by having advanced to approvals a pair of rare tumor-fighting drugs. One is Ogsiveo® (nirogacestat), a gamma secretase inhibitor indicated for adults with progressing desmoid tumors who require systemic treatment, approved by the FDA in 2023.

In February, SpringWorks won its second product approval for Gomekli™ (mirdametinib), indicated both for children ages 2+ and adults with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PNs) not amenable to complete resection. Gomekli is the first approved treatment for any form of NF1 in adults.

SpringWorks has also submitted a marketing authorization application for the drug that has been validated by the European Medicines Agency (EMA), with a Committee for Medicinal Products for Human Use (CHMP) recommendation expected in Q2 2025, potentially to be followed by approval later this year.

First in class

“It is the first in class. Obviously, we think we’re best in class for children, too,” SpringWorks CEO Saqib Islam told GEN Edge earlier this year.

Gomekli is the second FDA-approved drug for NF1. The first is AstraZeneca’s Koselugo® (selumetinib), which was authorized by the agency in 2020 solely to treat children ages 2 and older. Also focusing on NF1 is Healx, an artificial intelligence (AI)-based drug developer focused on treating rare diseases.

In February, Healx dosed the first patient in a Phase II trial (INSPIRE-NF1, NCT06541847) assessing its lead pipeline candidate HLX-1502 in NF1 patients with PNs, aggressive tumors linked to functional impairments and malignant transformation. HLX-1502 is an oral small-molecule mitochondrial dysregulator designed to prevent proliferation, growth, and viability of NF1 cells, and is being positioned by Healx as an alternative to existing treatments targeting the mitogen-activated protein kinase (MEK) pathway, such as Koselugo and Gomekli.

Along with the Gomekli approval, which occurred under Priority Review, the FDA also granted SpringWorks a pediatric disease priority review voucher (PRV) of undisclosed value. Gomekli previously received the agency’s Orphan Drug and Fast Track designations.

SpringWorks is studying additional development of the drug (under its generic name mirdametinib) in combination with BeiGene’s rapidly accelerated fibrosarcoma (RAF) dimer inhibitor (lifirafenib) in a Phase Ib/II trial in RAS/RAF mutant and other mitogen-activated protein kinase (MAPK) pathway aberrant solid tumors, and as a monotherapy in pediatric low-grade gliomas.

In gliomas, SpringWorks and St. Jude Children’s Research Hospital are partnering on the Phase II portion of a Phase I/II trial (NCT04923126) after sharing positive Phase I data at the 29th Annual Meeting & Education Day of the Society for Neuro-Oncology. “This MEK inhibitor is quite brain penetrant, which is why they [St. Jude] were originally interested in it, and that’s why they’re looking at it in that indication,” Saqib said.

Merck KGaA’s rare tumor focus was also evident last month, when the company exercised its option with Shanghai-based Abbisko Therapeutics to commercialize pimicotinib (ABSK021) in the United States and the rest of the world, in return for paying Abbisko an $85 million option fee.

Pimicotinib is an oral, highly selective small-molecule inhibitor of CSF-1R that is being developed to treat tenosynovial giant cell tumors (TGCTs), a group of rare, typically non-life-threatening tumors that involve the synovium, bursae, and tendon sheath, and which were previously known as pigmented villonodular synovitis (PVNS). Merck KGaA and Abbisko also agreed to explore pimicotinib in additional indications that include chronic graft-versus-host disease (cGvHD).

“Should accelerate sales growth”

“From a strategic perspective, we see the deal as a continuation of recent efforts to strengthen the oncology portfolio with a focus on rare tumors,” Thibault Boutherin, co-head of European Pharmaceuticals & Life Science equity research and an executive director with Morgan Stanley, and colleagues observed in a note, as reported by Bloomberg News. “The acquisition should accelerate sales growth of Merck’s healthcare division, which has been a key point of concern.”

Bloomberg Intelligence analyst Michael Shah has projected Merck KGaA will see up to €1.5 billion ($1.6 billion) in additional annual sales by 2030 from SpringWorks.

Merck KGaA generated €2 billion (about $2.3 billion) in sales from its oncology drug franchise last year, up 12.7% from 2023—but 60% of that sales volume came from a single drug, Erbitux® (cetuximab), which is indicated for forms of head and neck cancer as well as colorectal cancer. Erbitux lost European exclusivity in 2014 and U.S. exclusivity two years later, though no biosimilars of the drug have yet emerged.

For Merck KGaA, Erbitux racked up €1.2 billion (about $1.4 billion) in 2024 ex-U.S. and Canada sales, up 15.7% year-over-year (Eli Lilly markets Erbitux within the U.S. and Canada, but does not disclose its sales of that drug).

The cancer franchise accounts for 23.5% of total sales for Merck KGaA’s Healthcare business, which generated €8.5 billion (about $9.7 billion) last year, 7% organic growth from 2023, with earnings before interest, taxes, depreciation, and amortization (EBITDA) of €3 billion ($3.4 billion), a 22.7% organic sales jump from a year earlier.

“We see MRK KGaA Healthcare sales declining at 0.2% CAGR [compound annual growth rate] from 2025-28,” Anupam Rama, a U.S. biotech analyst with J.P. Morgan, noted in February.

One reason he cited was growing competition for Bavencio® (avelumab), a programmed death ligand-1 (PD-L1) blocking antibody indicated for forms of Merkel cell, urothelial, and renal cell cancers. The other reason is not cancer-related: Mavenclad® (cladribine), a purine antimetabolite indicated for relapsing forms of multiple sclerosis, faces expiration of two U.S. patents covering the 10 mg tablet in 2026, though a third does not expire until 2038.

“We have the unique opportunity with SpringWorks to establish a leadership position in rare tumors and build a strong foundation for further investments in this area, where a large unmet medical need exists,” said Peter Guenter, member of the executive board and CEO of Healthcare at Merck KGaA, Darmstadt, Germany. “For us, the planned acquisition will create long-term, sustainable growth for our healthcare business.”

Merck KGaA said its planned acquisition of SpringWorks will immediately add revenue and accelerate mid- to long-term growth for the buyer’s healthcare business. Last October, during its Capital Markets Day, Merck KGaA said it would continue to pursue external innovation via “in-licensing high-quality compounds at various stages of development”—as well as by “focused acquisitions that promise early value creation.”

21% stock surge

Investors jumped on SpringWorks stock last week as speculation about a buyout by German Merck resurfaced. SpringWorks shares surged 21% between April 21 and Thursday, from $37.06 to $44.93, before dipping 0.5% to $44.72 on Friday—a day after Merck KGaA re-confirmed it was in late-stage discussions with SpringWorks, in response to a report in The Wall Street Journal.

On Monday, after the deal was announced, SpringWorks shares on NASDAQ rose only 3% in early trading, to $46.18, and stayed flat early Tuesday, crawling to $46.19 as of 10:36 a.m. ET. Merck KGaA shares on the Deutsche Börse Xetra rose 0.6% Monday, from €122.25 ($139.27) to €122.95 ($140.23), then dipped 0.8% Tuesday to €121.95 ($139.08).

At $3.9 billion, the deal is far less than the $6 billion to $7.5 billion value range—$80 to $100 a share—for a SpringWorks buyout projected in February by Yaron Werber, MD, a managing director and senior biotechnology analyst with TD Cowen. Werber based his projection on 4–5x the projected $1.5 billion peak sales of both Gomekli and Ogsiveo, according to numerous published reports.

Higher sales projections for both drugs have since emerged. GlobalData’s Pharma Intelligence Center has projected a combined more than $1.7 billion in sales by 2030 for both SpringWorks drugs—$1.2 billion for Ogsiveo, $564 million for Gomekli. MKP Advisors has projected potential peak-year sales of $1 billion for Ogsiveo and Gomekli, Dow Jones has reported.

However, biotechs and pharmas are among companies affected by the overall stock market decline of recent months based on investor fears of U.S. tariffs triggering a recession, which has dented momentum for additional M&A deals that had been expected to build after a strong start to 2025, reflected in Johnson & Johnson’s $14.6 billion acquisition of Intra-Cellular Therapies.

Improving results

The prospect of a buyout by Merck KGaA is believed to explain why SpringWorks canceled a scheduled earnings call with analysts to discuss fourth-quarter and full-year 2024 results.

SpringWorks finished 2024 with a net loss of $258.1 million, a 21% improvement from its $325.1 million net loss in 2023, thanks to some of the $172.042 million in net product revenue generated by its Ogsiveo. The drug produced $5.447 million in net product revenue during its first month on the market in December 2023.

At $47 per share cash, the acquisition deal represents a 26% premium over SpringWorks’ unaffected 20-day volume-weighted average price of $37.38 on February 7, a day before market speculation emerged about a potential transaction between Merck KGaA and SpringWorks. Merck KGaA first confirmed talks with SpringWorks on February 11 after news of the potential deal was reported by Reuters.

The acquisition deal has been approved by the boards of both Merck KGaA and SpringWorks, and is expected to close in the second half of this year, subject to satisfying customary closing conditions, including approval by SpringWorks shareholders and regulatory approvals.

“Along with my successor Danny Bar-Zohar, we look forward to completing this strategic transaction and making a meaningful difference for patients whose lives are so profoundly affected by these complex and challenging tumors,” said Guenter, who will step down as Merck KGaA’s CEO of Healthcare effective June 1 in favor of Bar-Zohar, the Healthcare business’ global head of R&D and chief medical officer.

Headquartered in Stamford, CT, SpringWorks has “just under 400” employees, Saqib told GEN Edge, adding: “We’re not expecting very much headcount growth this year, given that we’ve already hired sales forces for Ogsiveo and for Gomekli as well. So, we expect pretty moderate and steady headcount through 2025.”

One of the AACR 2025’s opening plenary talks was presented by the brilliant Kevan M. Shokat, MD. His presentation has reminded me of his pioneering work on cell signaling networks and protein kinases, which fueled his transformational work in developing KRAS-targeted drugs. As I sit listening, I ponder the vast opportunities for new discoveries that could materialize this week from this “network” of cancer researchers I’m sitting amongst in this expansive hall.

With more than 20,000 attendees descending on the McCormick Place Convention Center this year, the collective knowledge across a panoply of cancers always strikes me as remarkably profound. I’m witnessing scientists assembled and connected by a common goal: to find cures for intractable cancers for the benefit of patients most in need.

Historically, cancer researchers were siloed and compartmentalized, distinct by their respective disciplines. Fortunately, today we see more unification in the cancer community, driven ostensibly by the shared multiple pathways that connect many of the cancers being discussed this week at AACR.

The second plenary talk by Paul Mischel, MD, gave an illuminating talk focused on extra-chromosomal DNA (ecDNA) and the implications for the amplification of oncogenes and drug resistance. He explained that ecDNA interferes with the immune response, so if we can find ways to block ecDNA, we may be able to stem the tide of cancer proliferation.

Johanna Joyce, PhD, then took the rostrum and spoke eloquently on the tumor microenvironment, underscoring the immense complexity of targeting key cell types and understanding clonal evolution, drug resistance, and the inherent issues cancer researchers face with brain tumor biology.

The final speaker, Catherine Wu, MD, discussed, with great clarity, the work her team is doing in ovarian cancer and cancer vaccines. She made the point that despite our efforts to deal with advanced diseases, we should be making moves to focus on cancer prevention. Wu hopes that in the near future every patient will receive cancer genomic profiling as a standard diagnostic workup, and she looks forward to a time when we can ensure patients have access to cancer vaccines as part of their routine clinical care.

All of this foundational research, of course, is contingent on funding. With recent catastrophic cuts by the current administration in the United States, the cancer research community has been left in a perilous situation. There are growing concerns about political interference, funding disruptions, and instability in the cancer research ecosystem, which ultimately threatens to undermine scientific progress. Actions to take in the stand against this existential threat were discussed during a panel session comprised of passionate past and present leaders from the NIH and AACR and patient advocates.

The discussion opened with the statement that, according to a Research America poll, the United States is a divided nation. The population may be separated by what they watch on Netflix or by what brands they like, but there are things Americans are unified in their opinions—namely, whether the federal government should support basic scientific research in the interests of advancing the frontiers of knowledge. Additionally, there is a majority consensus that the U.S. public is happy to supply more money via taxes to help fund innovation in scientific research.

Patricia LoRusso, DO, FAACR, who was serving her penultimate day as AACR president, gave an impassioned talk on the bleak implications of what these cuts will mean. She made the point that, “When researchers start altering proposals, not because the science is weak, but because the politics are difficult, something much deeper is lost.” Her passion was palpable as she continued to espouse evocative statements, and the audience was compelled to give a standing ovation.

Subsequent speakers followed in the same emphatic vein. Monica M. Bertagnolli, MD, addressed the audience not simply as a previous NIH director, but more importantly as a cancer survivor herself, underscoring that the continuity of clinical trials is essential to sustaining progress against cancer. Larry Saltzman, MD, is a retired physician and former executive research director for the Leukemia & Lymphoma Society, who had earlier been honored as a recipient of the 2025 Distinguished Public Service Award at the AACR Annual Meeting for his exceptional advocacy for NIH funding said, “I’m proof of what happens when Congress prioritizes decades of researchers, frontline providers, and a part of raising our voice to help those understand that investment in basic research is incredible.”

As I cast my eye around the auditorium, I was left with a feeling of regret that more attendees hadn’t been there to bear witness to such a great discussion. It was duly noted by Kristen Dahlgren, a former NBC journalist and cancer survivor, who made the point that we need to do a better job of articulating and disseminating the gravity of the situation—she felt that effective communication is clearly faltering. Dahlgren said, “There is a way to unite this country and unite people behind what you’re doing.”

Dahlgren knows better than most how communicating a story in the right way, to the right audience, is critical in building the requisite interest, engagement, and ultimately movement to effect change. To that end, she is working on a documentary highlighting the funding crisis we’re facing, so let’s hope this can create the groundswell for meaningful change. Whatever doubts lingered throughout this discussion, these seemed to dissipate through their collective indomitable spirit, and as LoRusso said, “Urgency is not a hypothetical variable.” Patients simply cannot wait, nor should they have to.

A research team from the UCLA Health Jonsson Comprehensive Cancer Center, the University of Texas MD Anderson Cancer Center, and collaborators have demonstrated that a novel topical BRAF inhibitor gel called LUT014 significantly reduces the severity of an acne-like rash, a common and painful side effect experienced by patients undergoing anti-EGFR therapies for colorectal cancer.

The results of the clinical trial, which the investigators say confirm the treatment’s safety and effectiveness, were discussed in an oral presentation at the AACR conference in Chicago.

“The findings offer the first real solution in two decades for managing this rash, which frequently impacts patients receiving targeted therapies for colorectal cancer,” said study co-author Zev Wainberg, MD, professor of medicine at the David Geffen School of Medicine at UCLA. “The ability to effectively treat it with a simple topical gel has the potential to greatly improve quality of life for patients and treatment outcomes.”

Anti-EGFR therapies, such as cetuximab and panitumumab, are a cornerstone of treatment for many cancers, including colorectal cancer. However, they often cause an acneiform rash that frequently leads to impaired quality of life and can lead to dose reductions or discontinuation of treatment, limiting their potential benefits, noted Wainberg.

LUT014, being developed by Lutris Pharma, works by paradoxically reactivating MAPK, a key signaling pathway in the skin that anti-EGFR therapies shut down. By applying the BRAF inhibitor gel directly to the affected areas, the gel helps restore skin function, reduce inflammation, and improve symptoms without impacting the anti-cancer effects of the treatment.

Approach and results

The Phase II double-blind, placebo-controlled, and randomized study enrolled 118 patients across 23 medical centers. Patients had colorectal cancer and developed moderate to severe rashes while taking cetuximab or panitumumab, two common anti-EGFR treatments.

The participants were randomly divided into three groups. One group used a low-dose gel, another a higher-dose gel, and the third used a placebo gel, which had no active drug. In each case, the gel was applied once a day for 28 days.

The main goal was to see if the rash improved, either by one level of severity or through better quality-of-life scores related to skin issues. The researchers found that patients using LUT014 gel experienced marked improvements in rash severity and quality of life compared to those receiving a placebo, without interfering with their cancer treatment.

Nearly 70% in the group using higher-dose gel saw their scores improve compared to about half (48%) of those using the low-dose gel and about one in three (33%) patients using gel with no active drug.

According to the scientists, it is now possible to alleviate skin toxicity without compromising the effectiveness of cancer treatment. This could help patients stay on their treatments longer, reducing the need for dose reductions or discontinuation, which in turn may improve overall treatment outcomes.

“Until now, patients were simply told that the rash was an unavoidable side effect of these treatments, something they had to endure for the sake of fighting their cancer,” said Antoni Ribas, MD, PhD, professor of medicine at the David Geffen School of Medicine and director of the tumor immunology program at the Jonsson Comprehensive Cancer Center, and a study co-author.

“But the data is overwhelmingly positive,” continued Ribas, who is also the founder and director of Lutris Pharma, the company that developed LUT014. “This approach not only improves patients’ quality of life but also makes the cancer treatment more manageable.”

Researchers headed by teams at the Garvan Institute of Medical Research and at the Kirby Institute at UNSW Sydney have discovered why receiving a vaccine booster in the same arm as the first vaccine dose can generate a more effective immune response more quickly. The researchers found that when a vaccine is administered, macrophage immune cells became ‘primed’ inside lymph nodes. These macrophages then direct the positioning of memory B cells (Bmems) to more effectively respond to the booster when given in the same arm.

The researchers say findings from their study in mice, which they validated in humans receiving a COVID vaccine, provide evidence to refine vaccination approaches and offer a promising new approach for enhancing vaccine effectiveness.

“This is a fundamental discovery in how the immune system organizes itself to respond better to external threats—nature has come up with this brilliant system and we’re just now beginning to understand it,” said Professor Tri Phan, MBBS, FRACP, FRCPA, PhD, Director of the Precision Immunology Program at Garvan. Scientia Professor Anthony Kelleher, MBBS, PhD, BSc, FRACP, FRCPA, FAAHMS, Director of the Kirby Institute, further commented, “A unique and elegant aspect of this study is the team’s ability to understand the rapid generation of effective vaccine responses. We did this by dissecting the complex biology in mice and then showed similar findings in humans. All this was done at the site of the generation of the vaccine response, the lymph node.”

Phan, and Kelleher are co-senior authors of the team’s published paper in Cell, titled “Macrophages direct location-dependent recall of B cell memory to vaccination.”

Immunization introduces a harmless version of a pathogen—the vaccine antigen—into the body. This is filtered through lymph nodes, which act as immune ‘training camps’ that train the body to fight off the real pathogen. “Vaccines protect from recurrent infection and disease by inducing the secretion of neutralizing antibodies by long-lived plasma cells (PCs) and by generating memory B cells (Bmems),” the authors noted. Phan and colleagues had previously discovered that the memory B cells, which are crucial for generating antibody responses when infections return, linger in the draining lymph node (dLN) closest to the injection site.

Using state-of-the-art intravital imaging at Garvan, the team discovered that, in mouse models, the memory B cells migrate to the outer layer of the local lymph node, where they interact closely with the macrophages that reside there. When a booster was then given in the same location, the primed subcapsular sinus macrophages (SSMs)—already on alert— efficiently captured the antigen and activated the memory B cells to make high quality antibodies. “… we tracked the migratory behavior and cell fate of Bmems in response to prime-boost vaccination with a model protein antigen,” the team explained. “Our data show that murine Bmems in the dLN reside in the subcapsular niche where they interact with SSMs, in contrast to ndLN [non-dLN] Bmems, which are located deeper in the follicle.”

The quality and quantity of the recall response to a second immunization was significantly higher when boosted in the dLN on the same side, compared with the ndLN on the other side. “These site-specific differences in the Bmem recall response were dependent on SSMs in the subcapsular niche,” the authors noted.

Study co-first author Rama Dhenni, PhD, who undertook the research as part of his Scientia PhD program at Garvan, commented, “Macrophages are known to gobble up pathogens and clear away dead cells, but our research suggests the ones in the lymph nodes closest to the injection site also play a central role in orchestrating an effective vaccine response the next time around. So location does matter.”
To determine the relevance of the animal results to human vaccines, the team at the Kirby Institute also conducted a clinical study with 30 volunteers receiving the Pfizer-BioNTech COVID-19 mRNA vaccine. 20 participants received their booster dose in the same arm as their first dose, while 10 had their second shot in the opposite arm. The results of analyses, the authors reported, indicated that “boosting of vaccine responses in the same arm as the priming dose generates superior depth and breadth of recall responses in the first week.”

Their collective data, the authors stated, “… show that primed SSMs control the quantity and quality of the Bmem recall response in the dLN and provide a rationale for administering the second dose of prime-boost vaccines in the same arm.”

Added Alexandra Carey-Hoppé, co-first author and PhD student from the Kirby Institute, “Those who received both doses in the same arm produced neutralizing antibodies against SARS-CoV-2 significantly faster—within the first week after the second dose.”

“These antibodies from the same arm group, were also more effective against variants like Delta and Omicron,” added Mee Ling Munier, PhD, co-senior author and Vaccine Immunogenomics group leader at the Kirby Institute. “By four weeks, both groups had similar antibody levels, but that early protection could be crucial during an outbreak.”

Munier added, “If you’ve had your COVID jabs in different arms, don’t worry – our research shows that over time the difference in protection diminishes. But during a pandemic, those first weeks of protection could make an enormous difference at a population level. The same-arm strategy could help achieve herd immunity faster—particularly important for rapidly mutating viruses where speed of response matters.”

Beyond the potential to refine vaccination guidelines, the findings offer a promising avenue for enhancing the effectiveness of vaccines. “If we can understand how to replicate or enhance the interactions between memory B cells and these macrophages, we may be able to design next-generation vaccines that require fewer boosters,” Phan pointed out. In their paper the authors concluded “These data reveal an unappreciated role for primed draining lymph node SSMs in Bmem cell fate determination.” From their results, they “… identify SSMs and their cell-cell communication with Bmems as potential cellular and molecular targets to improve the depth and breadth of antibody responses and vaccine efficacy.”

Have you ever wondered if there is a way to heal bones without having to take bone from another part of the body? A new doctoral thesis from the University of Borås, Sweden, now presents exciting advancements in this area. It involves using bacteria to produce fibers that can help heal bones.

Sabrina Kopf, Ph.D. in Polymer Technology, has investigated a special type of bioplastic, polyhydroxyalkanoates (PHA), produced by bacteria.

“The idea is to use these fibers in textile structures that can support bone healing in cases of large bone defects. For bones to heal, bone cells need something to attach to. Bone cells recognize the substance calcium phosphate. Therefore, we have added this substance to the fibers,” she explained.

The biggest challenge in the project was processing PHA into fibers with the equipment available in the laboratory. By melting the plastic and pressing it through a hole, similar to making spaghetti, she was able to produce fibers. These were then tested with bone cells to see if the cells could survive on the material.

“It turned out that it is possible to produce fibers with similar strength to bone. Additionally, we were able to produce simple knitted and woven textile structures from these fibers. The bone cells adhered to the material’s surface and appeared healthy, which is a good sign,” said Kopf.

Bone is, after blood, the second most transplanted tissue in the world, indicating a significant need for bone replacement materials.

“Today, bone from the patient’s own body is often used, meaning that bone is taken from, for example, the pelvis and transplanted to the damaged area in the body. This limits the amount of bone available. Additionally, the risk of complications at the donation site is high. Using synthetic materials like PHA fibers could be a solution to this problem,” said Kopf.

PHA fibers are also environmentally friendly. They can be produced from residuals and degrade in all types of environments without remaining as microplastics. This makes them a sustainable option for the future.

“The results of my project are a small step forward in biomedical research and can inspire other researchers to explore the potential of textiles in medical applications,” said Kopf.

Research at the University of Borås focuses on sustainable development based on global goals. Sabrina explained how this project connects to these goals: “Being able to produce fibers from PHA benefits not only the health care sector, even though that was the approach of my thesis. The fibers can also be used in other textile applications and contribute in all aspects where textiles are involved in the UN’s sustainable development goals, as PHA and its products are biodegradable and have no negative impact on the environment.”

Kopf will start as a researcher in melt spinning at RISE in the fiber development department, working with the same technology she used in her thesis.

When children lose their baby teeth, there is an adult set already growing beneath the gums, ready to emerge. But if we lose our permanent teeth, there aren’t any more waiting in the wings. Right now, the options for replacing these lost teeth are either dentures or titanium implants, neither of which provide the same function and feedback as a real, living tooth.

Pamela Yelick, AG89, a professor at Tufts University School of Dental Medicine, wants to be able to grow new, living teeth to replace those we’ve lost. In a paper published at the end of 2024 in Stem Cells Translational Medicine, Yelick and her colleagues showed that they could grow human-like teeth in pigs using a combination of human and pig tooth cells. The work is a significant step toward replacing dental implants with bioengineered living teeth.

Dental implants typically have a base of titanium, which is anchored into the jawbone. Titanium integrates well with bone, but it doesn’t have the soft tissue that surrounds a natural tooth root to cushion chewing forces and promote healthy bone turnover, or nerves to provide sensory feedback.

If the implant isn’t perfectly aligned, or a person is chewing too hard, the bone around the implant can start to break down and be absorbed back into the body. This creates opportunities for bacteria to reach the implant, which can accelerate bone resorption and eventually cause the implant to fail.

“Even creating a tooth root that you could put an artificial crown on—with living dental pulp in the middle, secured by periodontal ligaments instead of being screwed into the jaw—could be a huge improvement to a person’s oral health and in turn, systemic health,” says Yelick, who also holds appointments in the Graduate School of Biomedical Sciences and in the School of Engineering.

Prompting the body to grow new teeth isn’t easy. Our teeth start as a tooth bud—a little bulb of cells inside the jaw—which grows and differentiates into all the hard and soft tissues that make up a tooth and connect it to the jaw. The researchers needed to create their own bioengineered tooth bud with the right cell types and instructions to grow into a tooth on its own.

The tooth bud is made of two types of cells: dental epithelial cells, which produce tooth enamel, and dental mesenchymal cells, which eventually form the rest of the tooth, including the dental pulp, dentin, cementum, and periodontal ligament tissues.

Yelick and her team were able to collect dental mesenchymal cells from the pulp of extracted human wisdom teeth and other healthy teeth removed for orthodontic reasons, but dental epithelial cells are only present in the very early stages of tooth development. They can’t be collected from people once our teeth have been formed. They can, however, be collected from unerupted teeth present in pig jaws.

Unlike humans, pigs can grow multiple sets of adult teeth, so their adult jaws contain additional tooth buds. The researchers acquired pig jaws that would otherwise have been discarded from slaughterhouses and were able to extract tooth buds from them. They cultured these dental cells, as well as cells from human teeth, in the lab and then added them to a bioengineered scaffold that helped provide the necessary cues to start tooth development. Then they implanted these bioengineered tooth buds into the jaws of adult pigs, and monitored the animals for several months.

The researchers found that the bioengineered teeth developed at a similar rate as natural pig teeth, which is fairly close to that of human teeth. Because the experiment was only planned for three months, the teeth did not have a chance to emerge through the gums, but they underwent the same developmental stages as natural teeth.

“We found that we could make these beautiful little teeth,” Yelick says. “They’re still in the jaw—they haven’t erupted yet—but they look just like natural human teeth.”

Yelick and her colleagues hope to follow the tooth development for a longer duration in future experiments. They are also investigating the signaling molecules that direct cell behavior, looking for ways to initiate tooth growth from within the jaw instead of needing to extract and culture cells separately in the lab.

Their ultimate goal is to be able to prompt cells within a person’s jaw to grow new, entirely human teeth—no pig cells required. There is still more work to be done before the researchers are able to grow a living replacement for a human tooth, but Yelick thinks it is achievable in the next decade.

“Ideally, you keep your teeth as long as possible. That’s the best scenario,” Yelick says. “But if something happens, we hope to have biological tooth substitutes available.”

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.”

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 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.”

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.