Tag: Medicine

A new masking technology could expand the potential of antibody-based therapies for diseases such as Parkinson’s

Over the past few decades, antibody-based therapies have revolutionized modern medicine and are now widely used to treat cancer, autoimmune diseases, inflammatory disorders, and even infectious diseases. Despite their success, however, antibodies have a significant limitation: they struggle to penetrate cells and are therefore largely limited to targeting molecules located on the cell surface or outside the cell. In addition, antibody-based drugs have difficulty crossing the blood-brain barrier, restricting their use in treating diseases such as Parkinson’s and Alzheimer’s. Now, researchers at Tel Aviv University, together with colleagues, have developed a new technology that could overcome these barriers, enabling antibodies to reach the most important targets, those located inside the cell itself.

The technology was developed through a collaboration between research groups from Cornell University in the United States, Tel Aviv University, and the Technion. The study was led by Prof. Chris  A. Alabi and Prof. Matthew P. DeLisa from Cornell, collaborating with Prof. Avi Schroder from the Technion and TAU’s Prof. Ben Maoz of the Fleischman Faculty of Engineering and the Sagol School of Neuroscience and Prof. Uri Ashery of the Wise Faculty of Life Sciences and the Sagol School of Neuroscience, together with Prof. Christopher Alabi of Cornell. The findings were published in the Proceedings of the National Academy of Sciences (PNAS).

A Temporary “Mask” for Antibodies

In the study, the researchers developed an innovative approach based on temporarily “masking” the antibody using a synthetic molecule called SL4. This masking alters the antibody’s chemical properties in a controlled manner, allowing it to be encapsulated in lipid nanoparticles (LNPs), similar to the technology used to develop mRNA vaccines against COVID-19. Once the nanoparticles enter the cell, the antibody is released and regains its original structure and activity.

According to the researchers, this represents a significant breakthrough because approximately 80% of the proteins involved in human disease are located inside cells, making them inaccessible to most antibody-based therapies. The ability to deliver active antibodies into the cell cytoplasm opens new possibilities for treating diseases that have long been considered inaccessible to drug-based interventions.

The study demonstrated that the masking process significantly improves the efficiency with which antibodies can be encapsulated within lipid nanoparticles. Whereas unmodified antibodies were incorporated into the nanoparticles with relatively low efficiency, the masked antibodies achieved substantially higher encapsulation rates while retaining their stability and their ability to recognize the molecular target associated with the disease.

Reaching Targets Inside the Cell

The researchers tested the technology using a series of therapeutic antibodies targeting key biological pathways involved in disease development. The antibodies successfully entered cells and altered important signaling pathways associated with various types of cancer and inflammatory diseases. Following treatment, the activity of these pathways was significantly reduced, indicating that the antibodies had reached their intended targets and remained active inside the cells.

One of the study’s most promising findings emerged from a research model of Parkinson’s disease. The researchers used an antibody targeting alpha-synuclein, a protein whose accumulation in the brain is one of the hallmarks features of the disease. Following delivery of the antibody via the nanoparticles, they observed a significant reduction in the pathological aggregates of the protein in nerve cells, a finding that suggests that the technology could pave the way for new treatments for neurodegenerative diseases.

Beyond the Brain

The technology was also evaluated in a model of acute inflammatory lung injury. The researchers found that delivering antibodies via the lipid nanoparticles reduced inflammatory markers and improved pathological features of lung tissue. These findings highlight the potential for developing targeted therapies for severe inflammatory conditions.

Prof. Ben Maoz said: “For many years, delivering antibodies into cells has been considered one of the greatest challenges in the field of biologic therapies. We have succeeded in developing a system that enables antibodies to cross the cellular barrier and reach targets that were previously beyond their reach. We believe this is an important step toward expanding the therapeutic toolbox of modern medicine and paving the way for more precise treatments for complex diseases that still lack adequate therapeutic solutions.”

Toward a New Generation of Biologic Therapies

The researchers emphasize that the technology is still at the preclinical stage. Nevertheless, they believe the platform could lay the foundation for a new generation of biologic therapies. If it successfully progresses through development and clinical trials, it could, for the first time, enable the widespread use of antibodies against intracellular targets,  a goal widely regarded in the pharmaceutical industry as the next frontier of personalized medicine.

A new TAU technology identifies lung cancer’s biological fingerprint with more than 90% accuracy, without DNA sequencing, and could also help monitor patients’ response to treatment.

Researchers at Tel Aviv University have developed a new method for diagnosing lung cancer: a simple, fast, low-cost blood test that does not require DNA sequencing. The method identifies a chemical fingerprint of cancer cells in the blood, by analyzing cell-free DNA originating from those cells. In the study, the test distinguished between lung cancer patients and healthy individuals with a sensitivity of 93.1% and a specificity of 90.3% for patients with stage 2-4 disease.

The study was led by Prof. Yuval Ebenstein of the School of Chemistry at the Faculty of Exact Sciences, the Department of Biomedical Engineering and the Zimin Institute at Tel Aviv University, in collaboration with researchers from JaxBio Technologies, Bnai Zion Medical Center, and Sheba Medical Center. The paper was published in the journal Nature Precision Oncology.

A Different Approach to Lung Cancer Detection

Lung cancer is the leading cause of cancer-related death worldwide. At present, early diagnosis relies primarily on CT scans, but these tests generate a high rate of suspicious findings that ultimately prove to be benign, sometimes leading to unnecessary biopsies and surgeries. At the same time, existing liquid biopsies are generally based on DNA sequencing, a costly and complex process requiring advanced computational infrastructures.

The new method bypasses the need for DNA sequencing. After extracting cell-free DNA from a blood sample, the researchers label it with a light-emitting marker and bind it to a DNA chip they have developed. The chip is then scanned with an optical scanner, and the resulting light patterns are analyzed, enabling rapid identification of the biological fingerprint of lung cancer.

More Than 90% Diagnostic Accuracy

The study included 103 participants: 51 lung cancer patients and 52 healthy control subjects. Following a model-training phase, the researchers developed a signature of 170 genomic regions, and tested it on a separate validation cohort using blinded analysis, achieving high diagnostic accuracy. In addition, they were able to distinguish between the two main subtypes of lung cancer – adenocarcinoma and squamous cell carcinoma – based on distinct DNA signatures.

Could the Same Test Help Monitor Treatment?

Beyond diagnosis, the researchers also examined the novel test’s potential for monitoring patients’ response to treatment. Among the patients evaluated, changes in the DNA’s chemical fingerprint corresponded to imaging findings: in patients who responded to treatment, the chemical fingerprint shifted toward the profile of healthy individuals, whereas no significant change was observed in patients who did not respond to treatment. The researchers emphasize that this is only a preliminary finding and that large-scale studies are needed to confirm the method’s monitoring capabilities.

According to the researchers, the technology’s main advantage lies in combining simplicity, low cost, and speed. At present, the test can be completed within two to three days at a cost of approximately $60 per sample. They hope that in the future it will serve to complement imaging tests, assist in the early diagnosis of lung cancer, and enable more effective monitoring of treatment effectiveness.

Prof. Ebenstein concludes: “Our goal is to make blood tests for cancer diagnosis more accessible, simpler, and less expensive without compromising accuracy. We have developed a new approach that does not require genetic sequencing but instead identifies the tumor’s chemical ‘fingerprint’ with light, using a technology that can be implemented in standard clinical laboratories. This is a significant step toward developing a tool that can complement imaging tests and help physicians diagnose lung cancer and monitor treatment effectiveness.”

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A new analysis by TAU researchers found that an experimental treatment significantly slowed the progression of progressive supranuclear palsy (PSP) in women, highlighting the importance of sex-specific approaches to treating neurodegenerative diseases.

Researchers at Tel Aviv University have presented new findings indicating that the experimental drug Davunetide may significantly slow the progression of progressive supranuclear palsy (PSP) in women, who exhibited a markedly different response to treatment than men. These results reinforce the need for sex-specific medicine in neurodegenerative diseases.

The new publicarion, led by Prof. Illana Gozes of the Sagol School of Neuroscience and the Gray Faculty of Medical and Health Sciences at Tel Aviv University, used updated FDA-recommended outcome measures to reanalyze data from a 52-week international clinical trial involving more than 300 patients with PSP, a rare and fatal neurodegenerative disease caused by the abnormal accumulation of tau protein in the brain. There is currently no effective drug treatment for the disease.

The research team included current and former students Dr. Guy Shapira, Jason Blatt, and Liri Guz, together with Prof. Noam Shomron. The study was published in the prestigious journal Molecular Psychiatry from the Nature portfolio.

In contrast to the original conclusions of the clinical trial, which found that the drug was safe but ineffective, the researchers conducted an advanced and in-depth analysis that separated male and female participants and reexamined the data using updated assessment measures that are now recommended by the FDA. The results revealed a completely different picture: women treated with Davunetide experienced a significant slowing of disease progression, while no similar effect was observed in men.

Preserving Daily Function

The researchers found that the treatment helped preserve essential motor and functional abilities, including balance, fine motor skills, and everyday activities such as using cutlery, buttoning clothes, and washing the face and hands. In addition, the treated women showed significant improvements in cognitive measures, including language abilities, working memory, and overall cognitive function.

Different Disease Mechanisms in Women and Men

Another key finding of the study was the discovery of profound molecular differences between women and men. The researchers found that the relationship between the quantities of pathological tau in cerebrospinal fluid (a biomarker of the disease) and clinical symptoms was completely reversed between the two sexes. For example, language abilities significantly decreased with increased tau pathology in women, but not in men. This finding suggests that the disease mechanisms themselves may operate differently in women and men, potentially explaining their different responses to treatment.

According to Prof. Gozes, the study’s findings highlight that overlooking biological differences between the sexes may obscure genuine therapeutic efficacy.

“Our data show that analyzing women and men separately is not merely a statistical exercise, but an essential tool for developing more effective treatments for neurodegenerative brain diseases,” she says.

The researchers believe their findings provide a strong scientific basis for future clinical trials and for the future use of treatment protocols designed from the outset to account for patients’ sex, evaluating Davunetide as a targeted treatment for women with PSP. They say that this new approach may pave the way for the development of more precise medicine for patients with tau-related diseases, including the much more common Alzheimer’s disease and other neurodegenerative disorders of the brain.

The study was supported by ExoNavis Therapeutics, which is developing Davunetide for brain diseases under a license from Ramot, Tel Aviv University’s technology transfer company. Prof. Gozes serves as the company’s Vice President for Drug Development, and Dr. Guy Shapira serves as a consulting statistician. The results were independently validated by several additional statisticians.

A new Tel Aviv University study identifies the immune mechanisms behind eosinophilic gastritis and introduces one of the first experimental models of the disease, opening new avenues for future treatments.

Researchers at Tel Aviv University have developed one of the first experimental models that faithfully reproduces eosinophilic gastritis (EoG), a rare but increasingly recognized allergic disease of the stomach. Using this model, they identified the immune pathways responsible for driving the disease and explained why a new generation of biologic therapies currently being evaluated in clinical trials may benefit patients.

The study was led by Prof. Ariel Munitz and PhD student Anish Dsilva from the Department of Clinical Microbiology and Immunology at the Gray Faculty of Medical and Health Sciences, Tel Aviv University. The findings were published in Allergy, the world’s leading journal in clinical immunology.

Understanding a Poorly Understood Disease

Eosinophilic gastritis belongs to a family of disorders known as eosinophilic gastrointestinal diseases (EGIDs). The disease occurs when immune cells called eosinophils accumulate in the stomach, leading to chronic inflammation. Patients may suffer from abdominal pain, nausea, vomiting, early satiety, poor digestion, weight loss, and reduced quality of life. Although EoG is considered a rare disease, the number of diagnosed patients has increased substantially over the past decade, partly due to greater awareness and improved diagnosis. Despite this growing recognition, the biological mechanisms responsible for the disease have remained poorly understood, and treatment options remain limited.

Prof. Munitz explains:

“One of the greatest challenges in studying eosinophilic gastritis has been the lack of experimental models that accurately mimic the disease seen in patients. Without such models, it has been difficult to understand what causes the disease and, more importantly, to develop better treatments.”

Building a Model That Mimics the Disease

To overcome this challenge, the researchers developed a new mouse model that closely reproduces the key features observed in patients, including accumulation of eosinophils and mast cells, chronic inflammation, structural changes in the stomach lining, and tissue fibrosis. The new model now provides researchers worldwide with an important platform for studying this poorly understood disease and evaluating potential therapies.

The team then used the model to investigate two major immune signaling pathways controlled by the cytokines IL-4 and IL-13 molecules that play central roles in allergic diseases and are already targeted by several biologic drugs.

Their findings revealed that the two pathways perform remarkably different functions during disease development.

Two Pathways, Two Distinct Roles

Blocking IL-4Rα, a receptor that responds to both IL-4 and IL-13, dramatically reduced the accumulation of inflammatory cells in the stomach and prevented many of the structural changes caused by the disease. In contrast, eliminating IL-13Rα1, a closely related receptor, had little effect on inflammatory cell recruitment but significantly reduced the abnormal remodeling of stomach tissue.

“Although these two receptors have long been considered part of the same inflammatory pathway, we found that they actually perform distinct jobs,” says Prof. Munitz”. IL-4Rα acts as a master regulator that drives both inflammation and tissue damage, whereas IL-13Rα1 primarily controls how the stomach tissue remodels during disease”.

The findings are particularly timely because biologic therapies targeting IL-4Rα are already transforming the treatment of several allergic diseases, including asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and eosinophilic esophagitis. These therapies are now also being investigated in patients with eosinophilic gastritis.

“Our study provides a biological explanation for why therapies targeting IL-4Rα may be effective in eosinophilic gastritis,” says Prof. Munitz. “At the same time, it suggests that future therapies could become even more precise by targeting different pathways responsible for inflammation and tissue remodeling separately.”

Beyond its therapeutic implications, the researchers believe the new disease model represents an important resource for the scientific community.

“Developing new treatments begins with understanding how diseases work,” Prof. Munitz concludes. “By creating a model that closely resembles eosinophilic gastritis in humans, we now have a powerful tool for uncovering new therapeutic targets and accelerating the development of treatments for patients suffering from this challenging disease.”

New TAU study reveals how tumors reprogram immune cells to support their own growth, opening the door to new treatment strategies.

Researchers at Tel Aviv University’s Gray Faculty of Medical and Health Sciences have uncovered how a natural and essential immune system process can be hijacked to promote cancer progression. In a new study, the research team developed an advanced technology that enabled them to track macrophages, immune system cells, in real time and reveal how they alter their behavior within a cancerous tumor after consuming dead cancer cells. Their findings may pave the way for the development of new treatments targeting the specific macrophages identified in the study, restoring the immune system’s ability to fight the tumor instead of helping it.

The study was led by Dr. Merav Cohen and doctoral students Roi Balaban and Ori Moskowitz of the Gray Faculty of Medical and Health Sciences at Tel Aviv University. It was published in the prestigious journal Science Immunology.

When the Immune System Changes Sides

At the heart of the study are macrophages, immune cells whose role is to clear the body of damaged and dead cells. This process is essential for maintaining tissue health and preventing inflammation. However, the researchers discovered that within the environment of a cancerous tumor, this same mechanism can take an unexpected turn: instead of helping the body, it causes immune cells to adopt characteristics that actively support tumor growth.

To understand how this occurs, the researchers developed an innovative method called Effero-seq, which enables the tracking of changes that occur in immune cells after they engulf dead cells. Using this technology, the team found that as the process progresses, the immune cells undergo “reprogramming” and begin activating genes that promote tumor development.

Tracking Tumor-Supporting Immune Cells

Using a melanoma model, the researchers found that macrophages that had consumed dead cancer cells stimulated the formation of new blood vessels within the tumor. These blood vessels supply the tumor with oxygen and nutrients, enabling it to grow more rapidly. At the same time, these macrophages lost some of their ability to respond to signals that trigger anti-cancer immune activity.

The researchers also analyzed data from patients with uveal melanoma, a form of eye cancer. They found that patients whose tumors contained higher expression of immune cells bearing the genetic signature identified in the study tended to have lower survival rates.

According to Dr. Cohen, the findings provide a new perspective on how cancerous tumors manipulate their surroundings and harness the immune system for their own needs. “The better we understand these mechanisms, the better equipped we will be to develop treatments that block them and restore the immune system’s ability to fight cancer,” she says. “This research points to a new and promising therapeutic target, one that focuses not only on the cancer cells themselves, but also on the processes that enable them to thrive.”

Researchers developed an innovative therapy that reduces nerve cell damage after spinal cord injury and restored up to 80% of motor function in animal models

A new study led by Tel Aviv University offers real hope to millions worldwide affected by spinal cord injury (SCI), a devastating condition in which damage continues to spread after the initial trauma, often resulting in long-term and irreversible disability.

The study, recently published in the scientific journal Inflammation and Regeneration, presents an innovative therapeutic approach that reduces post-injury damage to nerve cells, reduces inflammation and scar formation, and therefore significantly improves functional recovery. The study was led by Dr. Angela Ruban from TAU’s Stanley Steyer School of Health Professions at the Gray Faculty of Medical & Health Sciences and the Sagol School of Neuroscience, together with Dr. Yona Goldshmit and students Josef Levin, Rosemary Lavender, Alexander Yakovchuk, Evgeny Banyas, and Ruth Baltovska. The findings were independently validated by a CRO as part of NeuroHagana’s preclinical development program, led by Dr. Amit Benbenishty.    

Stopping the Damage Before It Spreads

The researchers explain that one of the main problems in SCI is a process occurring within minutes of the injury: the accumulation of a neurochemical called glutamate that further damages nerve cells, generating a local inflammatory response, degeneration that leads to scarring and extensive progressive damage. To date, no treatment has been approved by FDA/EMA to stop this process and prevent a permanent disability. This is where the new method comes in, introducing a novel therapeutic approach: Instead of attempting to block harmful activity in the brain, the researchers found a way to remove excess glutamate through the bloodstream in the first hours after injury.

In experiments using animal models, the new treatment dramatically reduced post-injury glutamate levels, minimizing inflammation and nerve cell death, and preserving the structure of neural tissue, such as axons and synapses. Perhaps most impressive was the functional outcome: the treated animals showed marked improvement in walking and movement abilities within two days, achieving up to 80% of normal motor functioning two months after treatment – compared to around 30% in the untreated group.

The spinal cord treatment process in mice

A Treatment Designed for Real Emergencies

Another important advantage is the wide therapeutic time window: the researchers found that the treatment remains effective when given as long as eight hours after injury – a timeframe considered realistic in real-world medical emergencies. Administered via a simple intravenous injection, the treatment may feasibly be provided by first responders in the field, thereby halting the damage cascade in its earliest stages.

Dr. Ruban notes that the importance of the study “is not only the functional improvement, but the very ability to impact secondary damage — for which no effective treatments have been discovered so far. This suggests a potential for halting the ‘chain reaction’ that aggravates patients’ condition, thereby preserving neural functions that would otherwise be lost. If we are able to confirm our results in humans, the new approach will represent a true paradigmatic shift – from supportive care alone to treatment that actually reduces and maybe even completely prevents the extent of the damage.”

Beyond Spinal Cord Injuries

Dr. Goldshmit, an expert in SCI treatment and rehabilitation, adds that this novel method can revolutionize treatment not only for SCI, but also for other brain injuries, caused for example by stroke or trauma. Significantly reducing neural damage, the new treatment can enable much more successful rehabilitation later on.

According to Dr. Ruban, the events of October 7 and the ensuing war have created an additional target for the study: head injuries resulting from blast waves. Equipped with encouraging preliminary results in head injury models, the researchers will now test the treatment for blast-induced head injury in lab models through collaboration with the Neurotechnology Department of Israel’s Ministry of Defense and TAU Professor Chaim Pick of the Sylvan Adams Sports Institute, Sagol School of Neuroscience, and Gray Faculty of Medical and Health Sciences.  

Meanwhile, Ramot, TAU’s Technology Transfer Company, has established a commercial company to implement the breakthrough technology that redefines the treatment of both SCI and traumatic brain injuries (TBI): a simple intravenous injection with a wide therapeutic time window that reduces disability, improves quality of life, and significantly lowers costs for healthcare systems.

Dr. Ruban concludes: “Our main findings show that it is possible to intervene in the harmful process occurring immediately after injury — not just try to deal with its consequences after the fact. By reducing excess glutamate, we were able to protect nerve cells and significantly improve motor/cognitive functions in multiple preclinical models. If we can obtain similar results in humans, this study can potentially revolutionize the therapeutic approach to SCI and other neurological conditions. Together with other advanced medical and rehabilitation technologies being introduced into clinics, our innovation can help create a future in which SCI no longer condemns individuals to life in a wheelchair.”

For the first time, researchers uncover the biological mechanism that enables breast cancer to spread to the brain, opening new paths for treatment and early detection

A large-scale international study, led by researchers from the Gray Faculty of Medical and Health Sciences at Tel Aviv University, has uncovered a mechanism that allows breast cancer to send metastases to the brain — a highly lethal occurrence for which there is currently no effective treatment. The findings could enable the development of new drugs and personalized monitoring for early detection and treatment of brain metastases.

The groundbreaking study was led by Prof. Uri Ben-David and Prof. Ronit Satchi-Fainaro, along with researchers Dr. Kathrin Laue and Dr. Sabina Pozzi from their laboratories at the Gray Faculty of Medical and Health Sciences at Tel Aviv University, in collaboration with dozens of researchers from 14 laboratories in 6 countries (Israel, the United States, Italy, Germany, Poland, and Australia). The article was published in the journal Nature Genetics.

Why Do Some Cancers Spread to the Brain?

Prof. Satchi-Fainaro explains: “Most cancer-related deaths are not caused by the primary tumor but by its metastases to vital organs. Among these, brain metastases are some of the deadliest and most difficult to treat. One of the key unresolved questions in cancer research is why certain tumors metastasize to specific organs and not others. Despite the importance of this phenomenon, very little is known about the factors and mechanisms that enable it. In this study, we joined forces to deepen our understanding and seek answers.”

Left to right: Prof. Satchi-Fainaro & Prof. Uri Ben-David.

Combining Genetics and the Tumor Microenvironment

The current study combined two distinct approaches to cancer research: Prof. Satchi-Fainaro’s lab, which studies the interactions between cancer cells and their surrounding environment (the tumor microenvironment), and Prof. Ben-David’s lab, which investigates chromosomal changes that characterize cancer cells. The complex study involved numerous scientific methods and technologies, including clinical and genomic data analysis of tumors from breast cancer patients, genetic, biochemical, metabolic, and pharmacological experiments in cultured cancer cells, and functional experiments in mice.

The researchers first identified a specific chromosomal alteration in breast cancer cells that predicts a high likelihood of brain metastases. Prof. Ben-David explains: “We found that when chromosome 17 in a cancer cell loses a copy of its short arm, the chances of the cell sending metastases to the brain greatly increase. We also discovered that the reason for this is the loss of an important gene located on this arm. This gene is p53, often referred to as ‘the guardian of the genome,’ and it plays a crucial role in regulating cell growth and division. We discovered that the absence of a functional p53 is essential for the formation and proliferation of cancerous brain metastases. When we injected mice brains with cancer cells with or without functional p53, we found that cells with disrupted p53 activity thrived much more. We sought to understand the mechanism causing this.”

How Cancer Cells Adapt to the Brain Environment

Prof. Satchi-Fainaro adds: “The brain’s environment is fundamentally different from that of the breast, where the primary tumor develops, and the question is how a breast cancer cell, adapted to its original environment, can adjust to this foreign one. According to our findings, this adaptation is closely linked to the impairment of the p53 gene. We found that p53 regulates the synthesis of fatty acids, a metabolic process particularly vital in the brain environment. This means that cells with damaged p53, or without p53 at all, produce more fatty acids compared to normal cells, which in turn enables them to grow and divide more rapidly in the brain.”

Left to right: Dr. Kathrin Laue & Dr. Sabina Pozzi.

Hijacking Brain Cells to Fuel Tumor Growth

The next phase of the study focused on the components of the brain environment and the communication between brain cells and cancer cells. The researchers identified heightened interaction between cancer cells with damaged p53 and astrocytes — support cells in the brain that secrete substances aiding neurons. In the absence of p53, the cancer cells hijack the substances secreted by the astrocytes and use them to produce fatty acids. The researchers identified a specific enzyme named SCD1 — a key enzyme in fatty acid synthesis — whose expression and activity levels are significantly higher in cancer cells with impaired or missing p53.

Prof. Ben-David: “Once we identified the mechanism and its key players, we sought to use the findings to search for a potential drug for brain metastases. We chose to focus on the SCD1 enzyme and tested the effectiveness of several drugs that inhibit its activity and are currently under development. These drugs were originally indicated for other diseases, but we found that SCD1 inhibition in brain metastatic cells with impaired p53 was effective and significantly hindered the development and proliferation of cancerous metastases — both in mice and in samples from brain metastases of women with breast cancer.”

The researchers add that their findings may also assist doctors and patients in predicting disease progression: even at an early stage of breast cancer, it is possible to identify whether there is a p53 mutation (or deletion of the short arm of chromosome 17), which significantly increases the risk of brain metastases later on. For example, doctors could avoid prescribing aggressive biological treatments with severe side effects for patients not at high risk of brain metastases, while opting for aggressive treatment when the risk is elevated. In addition, physicians can tailor monitoring to the patient’s risk level — such as frequent brain MRI scans for patients at increased risk of brain metastases. This type of intensive monitoring would allow for early detection and treatment, significantly increasing the chances of recovery.

Looking Ahead

The researchers conclude: “In this study, we joined forces in an extensive international effort to address a highly important question: What is the mechanism that enables breast cancer to metastasize to the brain? We identified several characteristics of cancer cells causally linked to this deadly phenomenon, and the findings allowed us to propose new drug targets for brain metastases — a condition for which no effective treatment currently exists. Moreover, we tested drugs that inhibit a specific metabolic mechanism, SCD1 inhibitors, and found them to be effective against brain metastases. Additionally, our findings are expected to enhance oncologists’ ability to identify patients at elevated risk and prepare accordingly. While the road ahead is still long, the potential is immense.”

The project was supported by competitive research grants from the Israel Science Foundation (ISF), the Israel Cancer Research Fund (ICRF), and the Spanish bank Fundacion “La Caixa.” It is also part of broader research being conducted in Prof. Satchi-Fainaro’s lab, supported by an Advanced Grant from the European Research Council (ERC), ERC Proof of Concept (PoC), and the Kahn Foundation, as well as broader research being conducted in Prof. Ben-David’s lab, supported by an ERC Starting Grant.

TAU-led study uncovers how cancer cells disable the immune system

A new international study led by the Gray Faculty of Medical & Health Sciences at Tel Aviv University finds: melanoma cancer cells paralyze immune cells by secreting extracellular vesicles (EVs),

which are tiny, bubble-shaped containers secreted from a given cell. The research team believes that this discovery has far-reaching implications for possible treatments for the deadliest form of skin cancer.

How Melanoma Silences Immune Cells

This dramatic breakthrough led by Prof. Carmit Levy of the Department of Human Genetics and Biochemistry at TAU’s Gray Faculty of Medical & Health Sciences, in collaboration with research teams from Sheba Medical Center, the Weizmann Institute of Science, the University of Liège, the Technion, Tel Aviv Sourasky Medical Center, Wolfson Medical Center, Massachusetts General Hospital, Hadassah Medical Center, the Hebrew University of Jerusalem, Rabin Medical Center, Paris-Saclay University, and the University of Zurich. The study’s findings were published in the prestigious journal Cell.

Melanoma cells (green) are shown in co-culture with the patient’s own immune cells from Sheba Medical Center.

A New Role for Cancer-Secreted Vesicles

Melanoma is the deadliest type of skin tumor. In the first stage of the disease, melanocytic cells divide uncontrollably in the skin’s outer layer, the epidermis. In the second stage, the cancer cells invade the inner dermis layer and metastasize through the lymphatic and blood systems. In previous studies, Prof. Levy discovered that as they grow in the epidermis, melanoma cells secrete large extracellular vesicles (EVs) called melanosomes, which penetrate blood vessels and dermal cells, forming a favorable niche for the cancer cells to spread. The new study found that these vesicles also enable cancer cells to paralyze the immune cells that attack them.

“We began studying these vesicles,” says Prof. Levy, “and I noticed that on the vesicles membrane there was a ligand — a molecule that is supposed to bind to a receptor found only on immune cells called lymphocytes, specifically on lymphocytes that can kill cancer cells when coming into direct contact with them. I than hypothesis that this ligand latches onto lymphocytes that come to kill the melanoma. This was an innovative and odd idea and we start investigating it in the lab. When we got more and more evidence that this idea is correct, I spoke with colleagues around the world, and invited them to joined and contribute their expertise: from Harvard, from Sheba and from Ichilov’s pathology department, from the Weizmann Institute, from Zurich, Belgium and from Paris — all came together in a joint effort to decipher the cancer’s behavior. And the achievement is enormous: we discovered that the cancer essentially fires these vesicles at the immune cells that attack it, disrupting their activity and even killing them.”

Toward New Immunotherapy Strategies

Prof. Levy emphasizes that the remarkable discovery is promising however more work is require further in order to translate it into a new therapy. “We still have a great deal of work ahead of us, but it is already clear that this discovery can have far-reaching therapeutic implications,” says Prof. Levy. “It will enable us to strengthen immune cells so they can withstand the melanoma’s counterattack. In parallel we can block the molecules that enables vesicles to cling to immune cells, thereby exposing the cancer cells and making them more vulnerable. Either way, this study opens a new door to effective immunotherapeutic intervention.”

TAU meta-analysis finds pathogens, storms, and extreme temperatures are the leading causes of sea urchin mass mortality events.

Two pioneering studies by researchers from the School of Zoology and the Steinhardt Museum of Natural History at Tel Aviv University, led by Dr. Omri Bronstein, have identified the primary drivers of sea urchin mass mortality events over recent decades: pathogens, storms, and extreme temperatures. In addition, Dr. Bronstein and his team have developed an innovative method for genetic sampling in marine environments – using a swab similar to a COVID-19 test — to enable rapid and non-invasive monitoring of marine animals and underwater disease outbreaks.

The first study, published in the journal Biological Reviews, presents a meta-analysis of all 110 scientifically documented mass mortality events (MMEs) among sea urchins recorded between 1888 and 2024. Dr. Bronstein and PhD student Lisa Schmidt conducted a comprehensive review of the history of these events, showing that most reported MMEs originate in the Northern Hemisphere — particularly in the United States, Western Europe, and Japan — where the majority of research and funding are concentrated. The Tel Aviv University researchers classified five main causes of these events and found that 33% were caused by pathogens, 25% by catastrophic events such as storms and oxygen depletion, 24% by extreme temperatures, 11% by algal blooms, and 7% by human activity, such as pollution and habitat destruction.

Left to right: Mai Bonomo & Dr. Omri Bronstein holding sea urchin and sample tube

“This is a meta-analysis of all scientific literature on the subject,” says Dr. Bronstein. “For each mass mortality event, we mapped where and when it occurred, which species were affected, and most importantly — what the causes were. After filtering out hundreds of publications who lacked sufficient credible data to be included in our analyses, ee found that pathogens are the leading cause of mass mortalities among sea urchins. This finding aligns closely with what we are seeing today in the modern wave of die-offs — from the Caribbean to the Red Sea and the Indian Ocean. There is a tendency to attribute everything to global warming, but that is not always accurate. In many cases, mortality is not directly related to heat, as some affected sea urchin species naturally live in even warmer environments. These temperatures may not be optimal, but they are not lethal for these species. The problem is that warming influences many other environmental factors, which can combine into a deadly mix. For example, warmer waters tend to have lower dissolved oxygen and higher pathogen activity.”

A Global Sea Urchin Pandemic

In 2023, Dr. Bronstein identified a mass mortality event of long-spined sea urchins (Diadema setosum) along the Red Sea coast. He subsequently found that the same pathogen — a ciliate parasite — responsible for wiping out a related Caribbean species was also to blame. Since that discovery, the outbreak has spread to the Indian Ocean, reappeared in the Caribbean, and is now considered a global pandemic threatening sea urchin populations worldwide.

“Sea urchins are vital to coral reef health,” explains Dr. Bronstein. “They are the ‘gardeners’ of the reef: they feed on algae and prevent it from overgrowing and suffocating the corals competing for sunlight. In 1983, the most dominant Caribbean sea urchin species, Diadema antillarum, died in vast numbers from an unknown reason at the time; algae proliferated uncontrollably, shaded the corals, and the entire ecosystem shifted from coral reefs to algal fields. Even 40 years later, the sea urchin population — and the reefs — have not recovered. We fear that the same process may now occur in other parts of the world where mass die-offs are happening, mainly among the long-spined sea urchin, a relative of the Caribbean species — the black urchin with long spines familiar to everyone. Until recently, it was one of the most common reef urchins in Eilat; today it has almost disappeared from large parts of the Red Sea. This is a very violent event: within less than 48 hours, a healthy population turns into disintegrating skeletons. In some sites in Eilat and Sinai, mortality reached 100%. Later, mass deaths were recorded on Réunion Island in the Indian Ocean, and we are now investigating three additional mass mortality events in the Atlantic and Indian Ocean, and even the Mediterranean Seas. What began as a local mortality event has become regional and then global, posing a threat to coral reefs everywhere.”

Close-up of hand swabbing sea urchin underwater tank

The Challenge of Genetic Sampling Underwater

To address one of the major challenges in marine genetic sampling, graduate student Mai Bonomo and Dr. Bronstein published a separate study in Molecular Ecology Resources, developing a new, inexpensive, and non-invasive method for collecting underwater genetic samples at scale.

“The main tools used today to identify both animals and pathogens are genetic,” says Dr. Bronstein. “But molecular ecology faces a fundamental problem: there’s no simple way to sample DNA from live marine animals underwater. As a result, many studies rely on invasive methods that harm the animal or even require sacrificing it completely to bring it into the lab. Therefore, research in this field is heavily regulated, weighing each case’s scientific value against environmental ethics. For example, sampling is prohibited in marine nature reserves, there are restrictions and bans on shipping samples abroad — including corals — and every scientific publication must present the official permits for each sample it reports. Our need to overcome this bottleneck arose from the sea urchin pandemic. Today, there are only two ways to detect diseased urchins: visually — which is too late, as the animals are already dying — or through genetic tools that can detect disease before symptoms appear. But if detecting disease requires removing the animal from the sea, it makes no difference whether it’s sick or not — we end up sacrificing it.”

A Simple New Tool for Rapid, Non-Invasive Sampling

To overcome this challenge, Tel Aviv University researchers developed a specialized underwater genetic sampling kit that is durable, reliable, inexpensive, and easy to use — and it is already being adopted by research groups worldwide, especially in remote or sensitive areas.

“We developed a new tool for underwater DNA sampling that resembles a COVID-19 test,” explains Dr. Bronstein. “At the end of a special tube filled with a preservation liquid is a membrane preventing water penetration, sealed with a clip-cap — much like some toothpaste tubes. Just like a COVID test, the researcher gently swabs the surface of the marine animal, without harming or moving it. There’s no need to collect mucus as in humans — just a light swipe is enough. The swab is then inserted into the tube, piercing the membrane that protects the preservation liquid inside, and the cap is locked to secure the sample. That’s it. A single researcher can collect dozens of samples in one dive, under almost any environmental or depth conditions.

The kit has already been tested in challenging environments, including field expeditions to Djibouti and Réunion Island, and the results are very promising: samples remained exceptionally well-preserved for months without refrigeration before arriving at our lab, and still allowed for sensitive genetic analyses. In a large-scale trial we conducted in the Gulf of Eilat, we collected genetic material from hundreds of echinoderms — the group that includes sea urchins and starfish — within just a few months, and performed the most extensive genetic analysis ever conducted on these species in the region. This led to the discovery of several new species and the reclassification of others previously unknown to science. This is a simple and elegant solution to one of the most persistent technical challenges in marine molecular ecology.”