Science, Volume 392, Issue 6800, Page 814-814, May 2026.
Complex interplay of neuronal and hormonal gut-brain responses to essential amino acid deficit
Science, Volume 392, Issue 6800, May 2026.
Interacting effects of human presence and landscape modification on birds and mammals
Science, Volume 392, Issue 6800, Page 879-884, May 2026.
Precancerous Pancreatic Lesions May Not Always Lead to Cancer
Pancreatic cancer is an often deadly disease that, even if successfully treated, has a relative survival rate of about 13%, according to the NIH. When detected and treated early, that survival rate increases substantially. Developing strategies to diagnose cancer early or identify precancerous tissues is vital to success and increased survival.
A common precursor to pancreatic cancer is the presence of lesions called pancreatic intraepithelial neoplasia (PanIN). Researchers from the University of Michigan and the University of Maryland have been studying these precursor lesions and previously identified metabolic biomarkers involved with the development of PanIN to cancer. In their new study, published in Cancer Discovery, they expand their work into the PanIN microenvironments—the cells and tissues directly surrounding the lesions—to understand the cellular changes in an effort to find markers to use in diagnostics.
To examine the microenvironments, the team utilized single-cell RNA sequencing and spatial transcriptomics, isolating single cells and mapping their gene expression.
“These lesions are like needles in a haystack,” said co-senior author Timothy Frankel, MD, professor of surgical oncology and co-director of the Rogel and Blondy Center for Pancreatic Cancer at the University of Michigan. “The prior way of looking at this was to look at the entire haystack. You get a lot of information about hay and very little information about the needle.” He explained that using these precise techniques to examine cells individually is both more efficient and allows the researchers “to just focus in on the needle so we can look at multiple needles using the same amount of computing power and resources.”
The researchers used whole donated human pancreases to map the progression from PanIN to cancer, both for the precancerous and cancerous cells themselves, and the microenvironments surrounding them.
The pancreatic cancer microenvironment contains a highly diverse group of interactive cells, including fibroblasts and immune cells. The researchers found that while the epithelial tissue gene expression changes on a continuum from PanIN to cancer, the cells in the microenvironment are much more dynamic.
“Progression to cancer is accompanied by profound geographical reorganization of myeloid cells and lymphocytes and the formation of a cancer-specific fibroblast population characterized by high levels of Smooth Muscle Actin, LRRC15, and the WNT signaling component LEF1,” they wrote.
“It turns out, the microenvironment of these precursor lesions is the same as the microenvironment of the normal pancreas,” explained co-senior study author Marina Pasca di Magliano, PhD, professor of surgical immunology and co-director of the Rogel and Blondy Center for Pancreatic Cancer at the University of Michigan.
“The lesions have not convinced any of the cells around them to change. That’s not what we were expecting. We were expecting the two components, the cells and the microenvironment, to evolve in lockstep. They did not.”
These unexpected results indicate that there are other factors or stressors impacting the microenvironment. This is also in line with prior data showing that while pancreatic cancer is preempted by PanIN, not all, and in fact most, PanIN occurrences do not lead to a cancer diagnosis.
“It is incredible to see how we can uncover the fundamental cellular mechanisms of disease etiology by blending new computational methods and cutting-edge spatial transcriptomics technologies,” said co-corresponding author Elana J. Fertig, PhD, director of the Institute for Genome Sciences at the University of Maryland School of Medicine and associate director of quantitative sciences at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center. “Through careful study design, we can use the spatial information to start delving into the unknown dynamics of pancreatic tumor evolution.”
Moving forward, more research is needed to identify those stressors that may impact the microenvironment surrounding PanINs, which would allow the lesions to turn into cancers. Understanding those switches may open the door for developing earlier diagnostics or therapies to help prevent cancer development in the first place.
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AI Designs Miniprotein Switches for GPCR Targeting
Many scientists first encountered G protein–coupled receptors (GPCRs) as a looping sketch across the cell membrane in an early biology textbook. That simple diagram belied the complexity of a receptor family now known to govern vision, smell, hormone sensing, and the actions of countless medicines. Yet despite their centrality, designing molecules that can precisely switch GPCRs on or off has remained one of drug discovery’s most persistent challenges.
A new study led by the UW Medicine Institute for Protein Design and Skape Bio demonstrates that AI‑driven de novo protein design can finally meet that challenge. The work, published recently in Nature, shows that computationally designed miniproteins—compact proteins under 100 amino acids—can be engineered to either activate or block GPCRs with high affinity, potency, and selectivity. The paper is titled “De novo design of miniproteins targeting G protein-coupled receptors.”
The research team developed a suite of design strategies to create miniproteins capable of slipping into the deep, flexible pockets that govern GPCR signaling. These pockets shift shape depending on whether the receptor is active or inactive, making them difficult to target with conventional biologics. By designing molecules that recognize specific receptor states, the team generated agonists for receptors involved in itch and pain, and antagonists for receptors implicated in cancer, metabolic disease such as diabetes and obesity, and migraine.
“Protein design takes our understanding of how proteins fold and reverses it—asking if we can envision, with the aid of AI computing, a new protein that sticks to a target in a purpose-built way,” said senior author David Baker, PhD, director of the Institute for Protein Design, professor of biochemistry at the University of Washington School of Medicine, and a Howard Hughes Medical Institute Investigator. “This paper showcases how we can do this repeatedly for different GPCRs in ways that capitalize on their dynamic motion to either activate or inactivate them.”
Cryo‑EM structures of five designed miniproteins closely matched their computational models, underscoring the accuracy of the design pipeline. In one mouse study, a designed chemokine‑receptor antagonist mobilized hematopoietic stem and progenitor cells at levels comparable to a clinically used drug—but with fewer side effects, according to the authors.
For first author Edin Muratspahić, PhD, the moment of validation came when the designed molecules did more than bind. “Seeing computationally designed miniproteins not only bind but actually control GPCR signaling in living cells was a defining moment for me,” he said.
A second major advance reported in the study is a high‑throughput “receptor diversion” screening system that evaluates tens of thousands of designed proteins directly in living human cells. Traditional GPCR screens often require purifying or stabilizing receptors—steps that can distort their natural signaling behavior. By keeping receptors in their native membrane environment, the new system accelerates discovery while preserving biological relevance.
According to corresponding author Christoffer Norn, PhD, co‑founder of Skape Bio, the study lays out a roadmap for all‑computational design of GPCR ligands.
The methods described in the paper are already being adapted at Skape Bio to explore GPCR targets involved in metabolic, inflammatory, and neurologic pathways—areas where conventional discovery efforts have often struggled.
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STAT+: Closely watched experimental Parkinson’s drug fails key clinical trial
Biogen and Denali Therapeutics said Thursday that their experimental therapy for Parkinson’s disease failed to slow the degenerative brain disorder in a randomized trial, dealing a substantial blow to a scientific approach that stoked excitement among advocates and academics.
In the study, 648 adults with Parkinson’s were randomized to receive either a placebo or a pill targeting a protein called LRRK2. In 2004, researchers discovered that mutations in the LRRK2 gene can cause a rare, inherited form of Parkinson’s. And in 2018, another group of scientists showed that blocking the protein might actually benefit all patients with the disease.
Thursday’s results are a significant setback to the latter idea.
MyLungHealth, a Patient-Facing Education Tool for Lung Cancer Screening: Qualitative User-Centered Design Study
Background: Lung cancer remains the leading cause of cancer-related mortality worldwide, with low-dose computed tomography screening demonstrating an approximately 20% reduction in mortality among high-risk individuals. Despite this benefit, screening prevalence remains suboptimal, with often less than 20% of eligible individuals reported to be up to date on screening. Shared decision-making is essential for effective lung cancer screening (LCS) implementation, with decision aids shown to enhance patient knowledge and engagement. Objective: The aim of this study is to identify patient preferences, concerns, and design considerations through qualitative evaluation of MyLungHealth, a personalized patient-facing educational tool for LCS integrated with electronic health records, and to describe how these findings informed iterative design modifications. Methods: We employed qualitative research methods through focus groups (n=34) and individual interviews (n=18) with individuals who met screening eligibility criteria. Participants were recruited from the University of Utah Health and New York University Langone Health between May and December 2023. Feedback was analyzed using Braun and Clarke’s thematic analysis principles. Results: Six themes were organized into three overarching domains. Domain A included interpretation and impact of personalized risk information: theme 1, difficulties interpreting risk information, and theme 2, varied impacts of risk information on motivation. Domain B included autonomy, privacy, and user interface preferences: theme 3, desire for autonomy and control over personal health data, and theme 4, preference for straightforward language and multiple information formats. Domain C included integration with clinical workflows and patient portal systems: theme 5, expectations for integration with health care provider workflows, and theme 6, mixed experiences with personal health record systems. These insights led to key design modifications, including simplified risk presentation, multimodal content delivery options (video and text), and implementation of electronic health record alerts for clinicians. Conclusions: The user-centered design process for MyLungHealth revealed important considerations for developing effective patient education tools for LCS. The findings highlighted the need for simplified risk presentation, personalized information delivery, and integration with clinical workflows. These findings underscore the importance of balancing comprehensive risk communication with user accessibility. Trial Registration: ClinicalTrials.gov NCT06338592; https://clinicaltrials.gov/study/NCT06338592 International Registered Report Identifier (IRRID): RR2-10.1136/bmjopen-2024-087056
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STAT+: 3 burning questions senators had for the NIH director
Thursday’s Senate Appropriations Committee hearing was intended to focus on President Trump’s proposed budget for the National Institutes of Health’s fiscal year 2027 budget.
Instead, many of the senator’s questions for NIH Director Jay Bhattacharya and the five institute directors who joined him focused on more immediate concerns: a leadership vacuum at the agency’s sprawling infectious disease institute amid two outbreaks, the slow pace of funding over the course of the current fiscal year, and the impact of various Trump administration policies on the research community.
Here are three questions that were raised during the hearing:
STAT+: Merck-Kelun lung cancer drug cut risk of tumor progression by 65%, ASCO abstract shows
A type of targeted chemotherapy developed by China-based Kelun-Biotech and licensed to Merck cut the risk of tumor progression by 65% in patients with lung cancer, according to Phase 3 study results reported Thursday.
A preliminary survival benefit favoring the Kelun-Merck drug, called sacituzumab tirumotecan, or sac-TMT, was also seen in the study, but will require longer follow-up to confirm.
The study, conducted in China, is the first successful combination of an antibody-drug conjugate with a PD-1-targeted immunotherapy in patients with advanced but previously untreated non-small cell lung cancer.
Wacker Expands Service Offerings with Launch of Contract Research for Nucleic Acid-Based Therapies
Wacker reports that it is launching contract research services (CRS) at its biotech center in Munich for R&D-grade pDNA, RNA, and LNPs for preclinical studies. The new offering complements services of subsidiary CDMO Wacker Biotech, which has sites in Germany, the Netherlands, and the U.S.
In addition to producing pDNA, RNA, and LNP formulations, Wacker’s CRS team says it offers construct design services, including plasmid and RNA construct design as well as RNA engineering and optimization via partners, e.g., UTR, poly(A) and cap optimization. Company scientists also conduct lipid library screening and lipid nanoparticle formulation and provide functional assays and analytical services.
By integrating early-stage R&D support with a globally interconnected GMP manufacturing network, CRS helps customers streamline development and reduce supply-chain fragmentation, maintains a Wacker spokesperson. The approach enables an accelerated path from design to delivery in the field of advanced therapies, while lowering risk and cost through resourcing in early phases and a scalable transfer to Wacker Biotech for clinical material, continued the company official.
“Every RNA or LNP project is unique. Our goal is to provide flexible, customizable services that adapt to our clients’ specific needs in a rapidly evolving landscape,” explained Christian Dubiella, the CRS global program manager. “Too often, innovative, potentially life-saving therapeutic concepts die on the vine due to the high cost of developing even small amounts of drug substance for R&D studies. Our CRS enable us to serve highly specialized customers, especially small startups.”
One of CRS’ first customers is SRTD Biotech, an emerging biotech in Germany, which is starting small scale on novel therapeutic approaches.
“Our platform technology based on seRNAs (selectively expressed RNAs) can easily be adapted to numerous therapeutic areas by utilizing the transcriptome for selective cell targeting and fusogenic LNPs for organ-specific targeting,” said Bernd Hoffmann, CEO/CSO and cofounder of SRTD. “Wacker is an ideal partner on the road to realizing our vision of delivering seRNAs to patients to improve their lives.”
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