Researchers uncover possible new treatment to target a devastating childhood brain cancer

Professor Peter Lewis
Photo Credit: Courtesy of University of Wisconsin–Madison

Using fruit flies, University of Wisconsin–Madison researchers have developed a new model for investigating the genetic drivers of a rare but aggressive brain tumor in children. The work has already identified potential treatment targets for the deadly cancer that has previously had few therapeutic options.

“Right now, these tumors are incurable, and the standard of care hasn’t changed for 30 years,” says Peter Lewis, a professor in the Department of Biomolecular Chemistry.

The cancer is called pediatric diffuse midline glioma. As its name suggests, the malignancy arises along the midline of the brain or spinal cord and infiltrates surrounding tissue in a way that makes it impossible to remove with surgery. Instead, typical treatment revolves around radiation therapy, and that extends a patient’s life by just months or at most a few years.

Professor Peter Lewis: “What we found might extend well beyond these very rare childhood tumors into more common ones.”

The limited treatment options have driven researchers to more closely examine the genetic mutations that cause the cancer to develop in the first place, with an eye on finding ways to disrupt that process. 

In the case of diffuse midline glioma, previous research identified mutations in certain DNA-packaging proteins as a likely culprit.

Cholesterol-lowering drugs could reduce the risk of dementia

Low cholesterol can reduce the risk of dementia, a new University of Bristol-led study with more than a million participants has shown.

The research, led by Dr Liv Tybjærg Nordestgaard while at the University of Bristol and the Department of Clinical Biochemistry at Copenhagen University Hospital – Herlev and Gentofte, found that people with certain genetic variants that naturally lower cholesterol have a lower risk of developing dementia.

The study, which is based on data from over a million people in Denmark, England, and Finland, has been published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 

Some people are born with genetic variants that naturally affect the same proteins targeted by cholesterol-lowering drugs, such as statins and ezetimibe. To test the effect of cholesterol-lowering medication on the risk of dementia, the researchers used a method called Mendelian Randomization — this genetic analysis technique allowed them to mimic the effects of these drugs to investigate how they influence the risk of dementia, while minimizing the influence of confounding factors like weight, diet, and other lifestyle habits.

Air Pollution Can Contribute to Obesity and Diabetes

The most significant sources of fine air pollutants include exhaust fumes from cars, industrial plants and heating systems, as well as emissions from construction sites and forest fires.
Photo Credit: Uvi D

Long-term exposure to fine air pollution can impair metabolic health by disrupting the normal function of brown fat in mice. A study co-led by the University of Zurich shows that this occurs through complex changes in gene regulation driven by epigenetic mechanisms. The results demonstrate how environmental pollutants contribute to the development of insulin resistance and metabolic diseases.

There is growing evidence that air pollution is not just harmful to our lungs and heart, but also plays a significant role in the development of metabolic disorders like insulin resistance and type 2 diabetes. A new study co-led by Francesco Paneni, professor at the Center for Translational and Experimental Cardiology of the University of Zurich (UZH) and the University Hospital Zurich (USZ), and Sanjay Rajagopalan, professor at the Case Western Reserve University, Cleveland, now sheds light on the topic.

Researchers discover of a new type of diabetes in babies

Photo Credit: Rene Terp

Advanced DNA sequencing technologies and a new model of stem cell research has enabled an international team to discover a new type of diabetes in babies.

The University of Exeter Medical School worked with Université Libre de Bruxelles (ULB) in Belgium and other partners to establish that mutations in the TMEM167A gene are responsible for a rare form of neonatal diabetes.

Some babies develop diabetes before the age of six months. In over 85 per cent of cases this is due to genetic mutation in their DNA. Research led by the University of Exeter found that in six children with additional neurological disorders such as epilepsy and microcephaly identified alterations in a single gene: TMEM167A.

To understand its role, ULB researcher Professor Miriam Cnop’s team used stem cells differentiated into pancreatic beta cells and gene-editing techniques (CRISPR). They found that when the TMEM167A gene is altered, insulin-producing cells can no longer fulfill their role. They then activate stress mechanisms that lead to their death.

Engineered “natural killer” cells could help fight cancer

Caption:A new study identifies genetic modifications that make “natural killer” cells more effective at destroying cancer cells.
Image Credit: NIAID
(CC BY-NC-ND 4.0)

One of the newest weapons that scientists have developed against cancer is a type of engineered immune cell known as CAR-NK (natural killer) cells. Similar to CAR-T cells, these cells can be programmed to attack cancer cells.

MIT and Harvard Medical School researchers have now come up with a new way to engineer CAR-NK cells that makes them much less likely to be rejected by the patient’s immune system, which is a common drawback of this type of treatment.

The new advance may also make it easier to develop “off-the-shelf” CAR-NK cells that could be given to patients as soon as they are diagnosed. Traditional approaches to engineering CAR-NK or CAR-T cells usually take several weeks.

“This enables us to do one-step engineering of CAR-NK cells that can avoid rejection by host T cells and other immune cells. And, they kill cancer cells better and they’re safer,” says Jianzhu Chen, an MIT professor of biology, a member of the Koch Institute for Integrative Cancer Research,and one of the senior authors of the study.

Antibody discovered that blocks almost all known HIV variants in neutralization assays

Image Credit; Scientific Frontline / AI Generated

 A Cologne-led research team has discovered the antibody 04_A06, which neutralizes the human immunodeficiency virus (HIV) in almost all tested variants in vitro and even overcomes typical resistance mechanisms. The discovery potentially opens up new perspectives for the prevention and treatment of HIV infections.

An international research team led by the University of Cologne has discovered an antibody that could advance the fight against HIV. The newly identified antibody 04_A06 proved to be particularly effective in laboratory tests. It was able to neutralize 98.5 percent of more than 300 different HIV strains, making it one of the broadest antibodies against HIV identified. In experiments with humanized mice – animals whose immune system has been modified to resemble that of humans – 04_A06 permanently reduced the HIV viral load to undetectable levels. Most other HIV antibodies, in contrast, only achieve short-term effects in this animal model, as resistance develops quickly. The study ‘Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bNAb for HIV-1 prevention and therapy’ was published in Nature Immunology.

Chemists create red fluorescent dyes that may enable clearer biomedical imaging

Caption:MIT chemists have created a fluorescent, boron-containing molecule that is stable when exposed to air and can emit light in the red and near-infrared range. The dye can be made into crystals (shown in these images), films, or powders. The images at top were taken in ambient light and the images at bottom in UV light.
Image Credit: Courtesy of the researchers
(CC BY-NC-ND 4.0)

MIT chemists have designed a new type of fluorescent molecule that they hope could be used for applications such as generating clearer images of tumors.

The new dye is based on a borenium ion — a positively charged form of boron that can emit light in the red to near-infrared range. Until recently, these ions have been too unstable to be used for imaging or other biomedical applications.

In a study appearing today in Nature Chemistry, the researchers showed that they could stabilize borenium ions by attaching them to a ligand. This approach allowed them to create borenium-containing films, powders, and crystals, all of which emit and absorb light in the red and near-infrared range.

That is important because near-IR light is easier to see when imaging structures deep within tissues, which could allow for clearer images of tumors and other structures in the body.

“One of the reasons why we focus on red to near-IR is because those types of dyes penetrate the body and tissue much better than light in the UV and visible range. Stability and brightness of those red dyes are the challenges that we tried to overcome in this study,” says Robert Gilliard, the Novartis Professor of Chemistry at MIT and the senior author of the study.

New mechanism revealed: How leukemia cells trick the immune system

Thoas Fioretos, Niklas Landberg, and Carl Sandén are the research team behind the study now being published in Nature Cancer.
Photo Credit: Tove Smeds

A research team at Lund University in Sweden has discovered a mechanism that helps acute myeloid leukemia cells to evade the body’s immune system. By developing an antibody that blocks the mechanism, the researchers could restore the immune system’s ability to kill the cancer cells in laboratory trials and in mice. The discovery is published in Nature Cancer.

Immunotherapy has improved the treatment for many cancers, but progress has been limited in leukemia. Acute myeloid leukemia (AML) is particularly intractable, with a five-year survival rate of just over 30 per cent. The existing treatments are often aggressive and may include both strong chemotherapy and stem cell transplantations.

“We wanted to see if we could find surface proteins unique to leukemia stem cells, and which would therefore act as interesting targets for a targeted treatment. If such proteins were not present on healthy blood stem cells it might be possible to attack the tumor – without harming the healthy blood system,” says Thoas Fioretos, research group leader and professor of clinical genetics at Lund University, and senior consultant at Skåne University Hospital.

Scientists Have Created New Lanthanum Complex Promising for Anti-cancer Therapy

Lanthanum complexes demonstrate antioxidant activity, anti-inflammatory effect, acceleration of tissue regeneration and anesthesia.
Photo Credit: Louis Reed

As a result of the joint work of an international group of scientists from Russia (Ural Federal University), Bulgaria (Medical University, Sofia), and Spain (Complutense University of Madrid, Rey Juan Carlos University), a new lanthanum (III) complex with a luminescent triazole ligand has been obtained that is able to selectively regulate the level of reactive oxygen species (ROS) in cells. The result opens up prospects for the development of new anti-cancer and anti-infective drugs. The interim results of the study were published in the journal Molecules.

“New lanthanum complexes demonstrate a wide range of biological effects such as antioxidant activity, anti-inflammatory effect, acceleration of tissue regeneration and anesthesia. In a study that we conducted together with biologists from the Medical University of Sofia, we found out that both lanthanum complexes of La(III) and free organic ligands can affect the level of reactive oxygen species. At the same time, we found that they have a dual effect: in some tests, they act as antioxidants, protecting healthy cells, in others, as pro-oxidants, contributing to the death of tumor cells. This specific focus of action makes them promising candidates for the development of new drugs for cancer,” said Natalia Belskaya, Professor at UrFU Department of Technology pf Organic Synthesis.

Fat particles could be key to treating metabolic brain disorders

For decades, it was widely accepted that neurons relied exclusively on glucose to fuel their functions in the brain. This is not the case.
Photo Credit: The University of Queensland

Evidence challenging the long-held assumption that neuronal function in the brain is solely powered by sugars has given researchers new hope of treating debilitating brain disorders.

A University of Queensland study led by Dr Merja Joensuu showed that neurons also use fats for fuel as they fire off the signals for human thought and movement.

“For decades, it was widely accepted that neurons relied exclusively on glucose to fuel their functions in the brain,” Dr Joensuu said.

“But our research shows fats are undoubtedly a crucial part of the neuron’s energy metabolism in the brain and could be a key to repairing and restoring function when it breaks down.”

Dr Joensuu from the Australian Institute for Bioengineering and Nanotechnology along with lab members PhD candidate Nyakuoy Yak and Dr Saber Abd Elkader from UQ’s Queensland Brain Institute set out to examine the relationship of a particular gene (DDHD2) to hereditary spastic paraplegia 54 (HSP54).

Researchers use nanotubes to improve blood flow in bioengineered tissues

Assistant Professors Ying Wang (Department of Biomedical Engineering) and Yingge Zhou (School of Systems Science and Industrial Engineering) collaborated on research about engineered tissues.
Photo Credit: Jonathan Cohen.

When biomedical researchers need to test their latest ideas, they often turn to engineered human tissue that mimics the responses in our own bodies. It’s become an important intermediary step before human clinical trials.

One limiting factor: The cells need blood circulation to survive, and achieving that can be difficult in three-dimensional cell structures. Without proper vascular systems — even primitive ones — engineered tissue faces restricted size and functionality, even developing necrotic regions of dead cells.

New research from Binghamton University’s Thomas J. Watson College of Engineering and Applied Science offers a possible solution to the problem. In a paper recently published in the journal Biomedical Materials, Assistant Professors Ying Wang and Yingge Zhou show how the latest nanomanufacturing techniques can create a better artificial vascular system.

Simple test can predict risk of severe liver disease

The researchers' new method can contribute to earlier detection of cirrhosis and liver cancer.
Image Credit: Scientific Frontline / AI Generated

A new study from Karolinska Institutet, published in the scientific journal The BMJ, shows how a simple blood analysis can predict the risk of developing severe liver disease. The method may already start to be applied in primary care to enable the earlier detection of cirrhosis and cancer of the liver.

“These are diseases that are growing increasingly common and that have a poor prognosis if detected late,” says Rickard Strandberg, affiliated researcher at Karolinska Institutet’s Department of Medicine, Huddinge, who has developed the test with his departmental colleague Hannes Hagström. “Our method can predict the risk of severe liver disease within 10 years and is based on three simple routine blood tests.” 

For the study, the researchers at Karolinska Institutet and their colleagues in Finland evaluated how well the method can estimate the risk of severe liver disease. The model, which is called CORE, was produced with advanced statistical methods and is based on five factors: age, sex and levels of three common liver enzymes (AST, ALT and GGT), which are commonly measured during regular health checks. 

Study reveals how a single protein rewires leukemia cells to fuel their growth

IGF2BP3 IHC performed on a B-cell acute lymphoblastic leukemia (B-ALL) case; blasts are positive while normal hematopoietic cells are negative.
Image Credit: Courtesy of the Rao Lab.

Cancer cells are relentless in their quest to grow and divide, often rewiring their metabolism and modifying RNA to stay one step ahead. Now, researchers at the UCLA Health Jonsson Comprehensive Cancer Center have identified a single protein, IGF2BP3, that links these two processes together in leukemia cells. The protein shifts how cells break down sugar, favoring a fast but inefficient energy pathway, while also altering RNA modifications that help produce the proteins leukemia cells need to survive and multiply.

The discovery published in Cell Reports, positions IGF2BP3 as a “master switch” in leukemia, linking metabolism and RNA regulation, processes long thought to operate independently. Understanding this connection could pave the way for new therapies aimed at cutting off the energy and survival pathways that cancer cells depend on.

Unique pan-cancer immunotherapy destroys tumors without attacking healthy tissue

“It’s the holy grail – one treatment to kill virtually all cancers,” says Michael Demetriou.
Photo Credit: Steve Zylius / UC Irvine

A new, highly potent class of immunotherapeutics with unique Velcro-like binding properties can kill diverse cancer types without harming normal tissue, University of California, Irvine cancer researchers have demonstrated.

A team led by Michael Demetriou, MD, PhD, reported that by targeting cancer-associated complex carbohydrate chains called glycans with binding proteins, they could penetrate the protective shields of tumor cells and trigger their death without toxicity to surrounding tissue.

Their biologically engineered immunotherapies – glycan-dependent T cell recruiter (GlyTR, pronounced ‘glitter’) compounds, GlyTR1 and GlyTR 2 – proved safe and effective in models for a spectrum of cancers, including those of the breast, colon, lung, ovaries, pancreas and prostate, the researchers reported today in the journal Cell.

Study shows mucus contains molecules that block Salmonella infection

MIT researchers have discovered how mucins found in the mucus that lines the digestive tract can disarm the bacterium that causes Salmonella (purple).
Image Credit: Courtesy of the researchers
(CC BY-NC-ND 4.0)

Mucus is more than just a sticky substance: It contains a wealth of powerful molecules called mucins that help to tame microbes and prevent infection. In a new study, MIT researchers have identified mucins that defend against Salmonella and other bacteria that cause diarrhea.

The researchers now hope to mimic this defense system to create synthetic mucins that could help prevent or treat illness in soldiers or other people at risk of exposure to Salmonella. It could also help prevent “traveler’s diarrhea,” a gastrointestinal infection caused by consuming contaminated food or water.

Mucins are bottlebrush-shaped polymers made of complex sugar molecules known as glycans, which are tethered to a peptide backbone. In this study, the researchers discovered that a mucin called MUC2 turns off genes that Salmonella uses to enter and infect host cells.

Key driver of pancreatic cancer spread identified

A 3D tumor vessel-on-a-chip model, showing pancreatic cancer cells (green) invading an engineered blood vessel (red) by breaking down the vascular basement membrane (yellow).
Image Credit: Courtesy of Lee Lab

A Cornell-led study has revealed how a deadly form of pancreatic cancer enters the bloodstream, solving a long-standing mystery of how the disease spreads and identifying a promising target for therapy.

Pancreatic ductal adenocarcinoma is among the most lethal cancers, with fewer than 10% of patients surviving five years after diagnosis. Its microenvironment is a dense, fibrotic tissue that acts like armor around the tumor. This barrier makes drug delivery difficult and should, in theory, prevent the tumor from spreading. Yet the cancer metastasizes with striking efficiency – a paradox that has puzzled scientists.

New research published in the journal Molecular Cancer reveals that a biological receptor called ALK7 is responsible, by activating two interconnected pathways that work in tandem. One makes cancer cells more mobile through a process called epithelial-mesenchymal transition, and the other produces enzymes that physically break down the blood vessel walls.

Stronger together: a new fusion protein boosts cancer immunotherapy

An immune cell (small, orange) attacking a cancer cell (large, dark red).
Image Credit: M Oeggerli (Micronaut 2019), M P Trefny, and A Zippelius, Translational Oncology, University Hospital Basel, supported by Pathology University Hospital Basel, and Bio-EM Lab, Biozentrum, University of Basel

A newly developed molecule brings together two powerful immunotherapy strategies in one treatment. Researchers at the University of Basel and University Hospital Basel have demonstrated that this fusion protein can both block the “do not attack” signal used by cancer cells and selectively activate tumor-fighting immune cells. This dual action could pave the way for more effective cancer therapies with fewer side effects.

Back in the early 1980s, Linda Taylor, just 33 years old, was diagnosed with advanced skin cancer and faced a grim prognosis. Luckily, she met Dr. Stephen Rosenberg from the National Cancer Institute in Bethesda, Maryland, who treated her with an experimental approach harnessing the body’s own immune system to fight the disease. In 1984, Taylor became the first patient ever to be cured through immunotherapy – a groundbreaking case that forever changed the landscape of cancer treatment.

That pioneering therapy relied on interleukin-2 (IL-2), a signaling molecule that activates many types of immune cells to attack tumors. IL-2 later became the first immunotherapy approved by the U.S. Food and Drug Administration (FDA). However, while effective, IL-2 therapy often causes severe side effects and can also stimulate regulatory T cells, which dampen the immune response instead of boosting it.

Subtle cues between cells and immune system contribute to spread of cancer

Purdue University researcher John Tesmer is deciphering an intricate cell signaling system critical to immune response.
 Photo Credit: Alisha Willett / Purdue University

In the march of metastasis, a molecular trail of crumbs guides some cancer cells from the primary tumor to establish new colonies within the body. Blocking the cells’ ability to follow the trail might halt metastasis but could also meddle with an intricate cellular signaling system critical to immune response. Purdue University scientists are deciphering this signaling system to better understand how it could be used to address multiple diseases, including cancer.

Recent work, published in Nature, focused on a specific transaction inside the cell but is broadly applicable to how cells respond to signals from the endocrine system, a hormonal messaging system that influences metabolism, growth and reproduction and helps the body maintain homeostasis.

“There are multiple pathways inside a cell that are triggered by this messaging system and when they don’t work together properly, it promotes disease,” said research lead John Tesmer, the Walther Distinguished Professor in Cancer Structural Biology in the College of Science and a member of the Purdue Institute for Cancer Research. “Some of these pathways are useful, so ideally, we shouldn’t just turn off the signal at the source. But maybe we can find compounds that elicit a more nuanced response inside the cell, such as by preserving good pathways and dampening those that are bad.”

How Botox enters our cells

Volodymyr M. Korkhov (left) and Richard Kammerer of the Center for Life Sciences at PSI have made important advances towards understanding how botulinum neurotoxin, botox for short, enters our nerve cells.
Photo Credit: © Paul Scherrer Institute PSI/Mahir Dzambegovic

Botulinum toxin A1, better known under the brand name Botox, is not only a popular cosmetic agent, but also a highly effective bacterial neurotoxin that – when carefully dosed – can be used as a drug. It blocks the transmission of signals from nerves to muscles: This can relax muscles under the skin, which in cosmetics is used to smooth facial features. It can also alleviate conditions that are caused by cramping muscles or faulty signals from nerves, such as spasticity, bladder weakness, or misalignment of the eyes. However, if the dose is too high, the use of Botox can be fatal due to paralysis of the respiratory muscles. This can happen as a result of bacterial meat poisoning and is called botulism.

To make the most effective use of botulinum toxin as a drug, to precisely control its action, and to expand the range of possible applications of the toxin, researchers want to better understand how the toxin enters nerve cells to exert its effect. Until now, little was known about this.  “This is mainly because we had no structural data on what the toxin looks like in its full-length form when binding to its nerve cell's receptor,” says Richard A. Kammerer of the PSI Center for Life Sciences. So far there had only been studies on the structure of individual domains of the toxin – that is, specific parts of its complex molecular structure – and on the structure of such domains in complex with the receptor or one of its domains. 

Discovery of unexpected collagen structure could ‘reshape biomedical research’

Jeffrey Hartgerink is a professor of chemistry and bioengineering at Rice.
Photo Credit: Courtesy of Jeffrey Hartgerink / Rice University

Collagen, the body’s most abundant protein, has long been viewed as a predictable structural component of tissues. However, a new study led by Rice University’s Jeffrey Hartgerink and Tracy Yu, in collaboration with Mark Kreutzberger and Edward Egelman at the University of Virginia (UVA), challenges that notion, revealing an unexpected confirmation in collagen structure that could reshape biomedical research.

The researchers used advanced cryo-electron microscopy (cryo-EM) to determine the atomic structure of a packed collagen assembly that deviates from the traditionally accepted right-handed superhelical twist. Published in ACS Central Science, the study suggests collagen’s structural diversity may be greater than previously believed.

“This work fundamentally changes how we think about collagen,” said Hartgerink, professor of chemistry and bioengineering. “For decades, we have assumed that collagen triple helices always follow a strict structural paradigm. Our findings show that collagen assemblies can adopt a wider range of conformations than previously thought.”