According to the Cleveland Clinic, a quarter of cancer deaths can be attributed to one source: cachexia. Cachexia is a syndrome that accompanies underlying chronic illness and causes unwanted muscle and fat loss, reducing quality of life and sometimes even limiting treatment options.
A new study led by Thales Papagiannakopoulos, Ph.D., an incoming Salk professor, published in Science, points to a potential new target for preventing cachexia.
The researchers found that a common genetic subset of lung cancer is more prone to cachexia and that tumors from this subtype talk to the brain through sensory neurons in the lung. Silencing these sensory nerves to disrupt the tumor-to-brain connection reduced cachexia, as did blocking the production of the lipid signaling molecule prostaglandin E2 (PGE2) through dietary changes.
The researchers also built in a warning signal. When the cell received a confusing instruction—the biological equivalent of two commands arriving at once—it produced a separate alert instead of continuing as if nothing had happened.
To show how the system might one day be used in medicine, the team programmed cells to secrete IL-15, an immune protein that can help activate cancer-fighting immune cells.
The experiments relied on engineered circuits delivered into cells under controlled lab conditions. The authors note several challenges ahead, including avoiding unwanted RNA interactions, limiting leaky genetic switches, and finding reliable ways to insert larger circuits into cell genomes.
Nanoparticles are widely used in medicine to deliver drugs, genes or imaging agents to specific parts of the body. Once a nanoparticle reaches a cell, however, many things can happen—it can reach its target, be degraded, interact with proteins that help transport it, or interact with proteins that hinder its transport.
A longstanding problem in designing nanomedicines has been understanding what happens to nanoparticles at the cellular level, but scientists have faced many challenges. For example, optical microscopy imaging techniques provide only a generalized view of nanomedicine localization.
On the other hand, proteomics approaches require cell lysis, which disrupts the natural distribution of proteins around the nanoparticle, making it difficult to understand how nanoparticles are transported within the cell. Another method—proximity labeling—enables in situ investigation of intracellular protein-protein interactions, but it relies on genetically engineered enzyme fusion, which limits its applicability across diverse systems.
Researchers at the University of Bayreuth and Forschungszentrum Jülich have demonstrated that specific light-sensitive enzymes—so-called sensor histidine kinases (SHKs)—transmit their signal through a light-controlled change in asymmetry. With their new study, the researchers contribute to a better understanding of a central mechanism of bacterial signal processing. This may help develop new tools for biomedicine or biotechnology. The findings are reported in the journal Science Advances.
SHKs are key bacterial signaling proteins that play an important role in many processes, from controlling which genes are active at a given time to enabling the ability to cause disease. Artificially engineered light-sensitive SHKs are also used in optogenetics to precisely control gene activity with light. However, only limited structural information has been available so far for the full protein.
The new study provides important insights into how natural and engineered SHKs transmit signals across multiple protein domains. In the long term, the study may help develop new optogenetic tools that allow biological processes to be precisely controlled using light. This is particularly relevant for applications in biotechnology and biomedicine.
Human trisomy 21, responsible for Down syndrome, is the most prevalent genetic cause of cognitive impairment and remains a key focus for prenatal and preimplantation diagnosis. However, research directed toward eliminating supernumerary chromosomes from trisomic cells is limited. The present study demonstrates that allele-specific multiple chromosome cleavage by clustered regularly interspaced palindromic repeats Cas9 can achieve trisomy rescue by eliminating the target chromosome from human trisomy 21 induced pluripotent stem cells and fibroblasts. Unlike previously reported allele-nonspecific strategies, we have developed a comprehensive allele-specific (AS) Cas9 target sequence extraction method that efficiently removes the target chromosome. The temporary knockdown of DNA damage response genes increases the chromosome loss rate, while chromosomal rescue reversibly restores gene signatures and ameliorates cellular phenotypes. Additionally, this strategy proves effective in differentiated, nondividing cells. We anticipate that an AS approach will lay the groundwork for more sophisticated medical interventions targeting trisomy 21.
Keywords: CRISPR/Cas; Down syndrome; allele specificity; chromosome cut; chromosome loss; human trisomy 21.
© The Author(s) 2025. Published by Oxford University Press on behalf of National Academy of Sciences.
A newly discovered microbe is like a mini version of the Hulk.
Euplotes gigatrox is a single-celled protist that resembles an insect. It grazes on bacteria and other tiny microbes. Sometimes a small number of the protists balloon into “supergiants” more than twice their regular size. The huge cells cannibalize their smaller, genetically identical brethren. The triggers for the change aren’t entirely clear, but it tends to happen when there is plenty of food, researchers reported May 14 in the Proceedings of the National Academy of Sciences.
Hereditary hearing loss affects millions globally, with mutations in the SLC26A4 gene among the most common genetic triggers, particularly across Asian populations. This condition leads to severe-to-profound deafness accompanied by inner ear malformations, such as an abnormally enlarged vestibular aqueduct and endolymphatic sac.
While gene replacement therapies have long held immense potential, experimental interventions have historically been restricted to the embryonic stage. Delivering genetic material before birth presents steep ethical and practical hurdles, creating a critical roadblock for real-world medical applications.
A new study by researchers at the Icahn School of Medicine at Mount Sinai overturns a longstanding assumption about how mRNA vaccines generate immunity, revealing that certain non-immune cells help determine vaccine effectiveness.
The study, published in Nature Biotechnology, also introduces a powerful and versatile technology to control the expression of mRNA drugs, which the researchers demonstrate can enhance the effectiveness of mRNA cancer vaccines in preclinical studies of lymphoma. The paper is titled “mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression.”
The findings provide a new framework for designing mRNA vaccines and mRNA therapeutics, with immediate implications for cancer immunotherapy, infectious disease vaccines, and gene-editing treatments.