Tag: Medicine

Prof. Isaac P. Witz Honored with 2023 Szent-Györgyi Prize for Progress in Cancer Research

Written by AUFTAU on 26 June 2023. Posted in Magazine.

An Impressive achievement: Professor Isaac P. Witz from the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University’s George S. Wise Faculty of Life Sciences, was chosen by the prize selection committee of the National Foundation for Cancer Research (NFCR) in the US to receive the prestigious Szent-Györgyi Prize for his groundbreaking scientific contributions.

Groundbreaking Discoveries

The prize will be given to Prof. Witz, a distinguished figure in cancer research, whose work has shed light on the crucial role of reciprocal information flow and signaling between cancer cells and the tumor microenvironment (TME) for understanding tumor formation, progression and metastasis. The annual Prize honors scientists whose seminal discovery or pioneering body of work has contributed to cancer prevention, diagnosis, or treatment and has had a lasting impact on understanding cancer, holding the promise of improving or saving lives of cancer patients. In recognition of his achievements, Professor Witz will receive the award at a ceremony scheduled for October 21, 2023, at The National Press Club in Washington, D.C.

“I am filled with immense gratification knowing that my contributions have shaped current understanding of the TME and laid the foundation for life-saving immunotherapies for patients.”– Prof. Isaac Witz

Professor Isaac Witz expressed his profound satisfaction, stating: “I am filled with immense gratification knowing that my contributions have shaped current understanding of the TME and laid the foundation for life-saving immunotherapies for patients. It is an absolute honor, and I am overwhelmed with joy and gratitude towards the 2023 Szent-Györgyi Prize Selection Committee for bestowing upon me this prestigious recognition, allowing me to stand alongside the esteemed previous recipients of the Szent-Györgyi Prize.”

With an outstanding career spanning over fifty years, Professor Witz currently serves as Professor Emeritus at Tel Aviv University and heads the Laboratory of Tumor Microenvironment & Metastasis Research at The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences. Throughout his career, he made significant contributions through breakthrough observations, discoveries, publications, and collaborative efforts, emphasizing the critical role of the TME in cancer cell biology, growth, and metastasis.

Impactful Research

During the early stages of his scientific journey, in the 1960s, Professor Witz pioneered the TME concept by an experimental demonstration that components of the immune system infiltrate the TME, impacting tumor behavior. His research established that humoral immune factors localized in the TME exert pivotal roles on various manifestations of anti-tumor immune responses. These seminal findings laid the groundwork for certain aspects of contemporary life-saving immunotherapies, ultimately benefiting cancer patients and advancing scientific progress towards finding cures for cancer.

Rakesh K. Jain, Ph.D., Chair of the 2023 Selection Committee and the 2022 Prize recipient, expressed his delight at Professor Witz’s selection, highlighting the impact of his work on the development of cancer therapeutics targeting molecules within the TME. Dr. Jain, whose own research encompasses the field of TME, believes that future opportunities for life-saving therapies will continue to emerge from this area of study.

A Step Closer to Beating Melanoma?

Written by AUFTAU on 18 June 2023. Posted in Newsroom.

New study reveals critical insights in fight against skin cancer.

A new study conducted at Tel Aviv University and the Sheba Medical Center reveals how melanoma cancer cells affect their close environment to support their needs – by forming new lymph vessels in the dermis to go deeper into the skin and spread through the body. The researchers believe that the new discovery may contribute to the development of a vaccine against the deadly cancer.

The Hidden Mechanism

The scientific breakthrough was led by Prof. Carmit Levy of Tel Aviv University’s Sackler Faculty of Medicine and Prof. Shoshana Greenberger from the Sheba Medical Center. The study was funded by ICRF (the Israel Cancer Research Fund) and its results appeared in the Journal of Investigative Dermatology published by Nature.

“We demonstrated for the first time that in the first stage, in the epidermis, melanoma cells secrete extracellular vesiculas called melanosomes.” – Prof. Shoshana Greenberger

The researchers (from left): Prof. Carmit Levy and Prof. Shoshana Greenberger

Melanoma, the deadliest of all skin tumors, starts with uncontrolled division of melanocyte cells in the epidermis – the top layer of the skin. In the second stage the cancer cells penetrate the dermis and metastasize through the lymphatic and blood systems.

In previous studies a dramatic rise was observed in the density of lymph vessels in the skin around the melanoma – a mechanism that was not understood by researchers until now.

“Our main research question was how melanoma impacts the formation of lymph vessels, through which it then metastasizes,” explains Prof. Greenberger. “We demonstrated for the first time that in the first stage, in the epidermis, melanoma cells secrete extracellular vesiculas called melanosomes.”

What are these vesiculas and how do they impact their environment? Examining this in human melanomas from the Pathology Institute, the researchers demonstrated that melanosomes could penetrate lymph vessels. They then examined their behavior in the environment of actual lymph vessel cells and found that here too the melanosomes penetrate the cells and give them a signal to replicate and migrate. In other words, the primary melanoma secretes extracellular vesiculas that penetrate lymph vessels and encourage the formation of more lymph vessels near the tumor, enabling the melanoma to advance to the lethal stage of metastasis.

“If we can stop the mechanisms that generate metastases in lymph nodes, we can also stop the disease from spreading” – Prof. Shoshana Greenberger

Melanoma’s Stealth Tactics

Prof. Carmit Levy adds that, “melanoma cells secrete the extracellular vesiculas, termed melanosomes, before cancer cells reach the dermis layer of the skin. These vesicles modify the dermis environment to favor cancer cells. Therefore, melanoma cells are responsible for enriching the dermis with lymph vessels, thereby preparing the substrate for their own metastasis. We have several continuing studies underway, demonstrating that the melanosomes don’t stop at the lymph cells, as they also impact the immune system, for example.”

A Promising Vaccine Hope

Since melanoma is not dangerous at the premetastatic stage, understanding the mechanism by which the metastases spread via the lymphatic and blood systems can hopefully contribute to the development of a vaccine against this deadly cancer.

“Melanoma that remains on the skin is not dangerous,” says Prof. Greenberger. “Therefore, the most promising direction for fighting melanoma is immunotherapy: developing a vaccine that will arouse the immune system to combat the melanosomes, and specifically to attack the lymphatic endothelial cells already invaded by the melanosomes. If we can stop the mechanisms that generate metastases in lymph nodes, we can also stop the disease from spreading.”

Imagining the Future Patient

Written by AUFTAU on 13 June 2023. Posted in Newsroom.

Biomedical and technological progress is at the tipping point of transforming medicine into a more precise, proactive science capable of defeating human disease.

The 21st century is revolutionizing our approach to healthcare, our understanding of the human body, and our ability to intervene in its most intricate processes. Tel Aviv University researchers are at the forefront of the advancing changes. They are collaborating with Israel’s hospitals and industry to compute a patient’s future, popularize genetic screenings, develop novel vaccines, and usher in the era of truly personalized treatment.

Transforming Sick Care into Health Care

The last decade has seen an explosion in the amount of electronic medical records. Around the world, massive databases containing comprehensive genetic and health information on hundreds of millions of people have been collected at hospitals, clinics, and data repositories. Alongside it, the revolution in AI is enabling the development of computational tools to accurately analyze this data on an unprecedented scale. At this intersection, the field of bioinformatics, which aims to solve biomedical problems by using computer science tools, is becoming increasingly important in transforming medicine from a reactive to a proactive science.

“It became obvious very fast that analyzing this data would provide fantastic insights to understanding how disease transpires and progresses, and to offer novel approaches to diagnosis, treatment, and prevention,” says Ron Shamir, Professor Emeritus of the Blavatnik School of Computer Science at the Raymond and Beverly Sackler Faculty of Exact Sciences and the founding director of TAU’s Edmond J. Safra Center for Bioinformatics and Koret-Berkeley-TAU Initiative in Computational Biology and Bioinformatics. The Edmond J. Safra Center for Bioinformatics brings together all bioinformatics-related research and teaching activities across campus into one multidisciplinary hub, spanning over 50 research groups and 200 students across four faculties.

“A single individual’s genome is three billion letters. Working with this amount of data feels like drinking from a fire hydrant at times” – Professor Emeritus Ron Shamir

Navigating the Data Labyrinth

Data is the backbone of all bioinformatics research but it’s not an easy work partner—sometimes its sheer amount and complexity are overwhelming. “A single individual’s genome is three billion letters. Working with this amount of data feels like drinking from a fire hydrant at times,” Shamir says.

To assist TAU researchers in addressing this problem and questions of data privacy and security, TAU recently established the Health Data Science Hub — a joint unit of the Edmond J. Safra Center for Bioinformatics, TAU’s AI & Data Science Center, the Sackler Faculty of Medicine, and the Biomedical Engineering Department at The Iby and Aladar Fleischman Faculty of Engineering.

“The Hub will be the center of knowledge and expertise on the various protocols needed to access large data repositories and will streamline the process for TAU scientists, which will be a great help in facilitating research,” explains current Head of Edmond J. Safra Center for Bioinformatics, Prof. Elhanan Borenstein, of the Blavatnik School of Computer Sciences and the medical faculty.

“To advance the future of medicine, we need to broaden the set of tools physicians use to understand a patient’s medical situation. Researchers and physicians need to talk to each other.” – Prof. Elhanan Borenstein

Physicians of the Future

Another long-term mission of TAU’s bioinformatic programs is to educate physicians about the potential of digital medicine.

To achieve this, TAU introduced several novel study programs in the 2022-23 academic year. First, a joint Bioinformatics-MD degree, which will arm future doctors with advanced data crunching skills. Another is a Big Data in Healthcare course offered by the Faculty of Medicine in collaboration with a governmental and industry consortium called the “8400 Health Network.” The course allows participants, many of whom are practicing physicians, to become acquainted with the opportunities now available to them in the digital healthcare realm. A total of 480 candidates applied for the 80 spots available in the course pilot.

“To advance the future of medicine, we need to broaden the set of tools physicians use to understand a patient’s medical situation. Researchers and physicians need to talk to each other,” Borenstein explains. To facilitate this, the Edmond J. Safra Center for Bioinformatics spearheads dozens of collaborative projects in clinical bioinformatics with various hospitals, programs, and academic institutions. It awarded 22 grants in the last two years for joint research projects, and an additional five collaborative grants are expected to be awarded in the coming months.

Preventive Genetics

One example of such a collaboration is Prof. Ran Elkon’s lab at the Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine. Elkon’s work centers on understanding the genetic basis of widespread complex diseases, such as high blood pressure, stroke, cancer, cardiovascular diseases, diabetes, and even mental illnesses.

Prof. Ran Elkon

“These diseases are not considered genetic as the term is commonly understood, but it’s clear that they have a genetic component, which we call ‘predisposition,’” says Elkon. Rather than single-gene mutations, hundreds of small genetic variations influence the risk of contracting such diseases, he explains. “Each individual variant has very little effect on its own; what matters is the collective amount of such ‘risk variants’ in each individual genome.”

Elkon’s lab team recently completed a project on identifying women with an elevated genetic predisposition to breast cancer and showed that findings are applicable in Israel. Elkon is now working with Israel’s largest HMO, Clalit, to launch a clinical study for identifying such women among Clalit’s clients and offering them a more personalized breast cancer screening strategy.

“With genetic testing, we can develop more personalized, more precise approaches that will be much more effective for prevention and early detection of [breast cancer].” – Prof. Ran Elkon

The likelihood of developing breast cancer is 16 times higher for women in the top 1% genetic risk group compared to those in a low-risk group. However, today in the developed world, healthcare providers offer identical screening recommendations and coverage for women on both ends of the spectrum, Elkon explains. “We are trying to change this one-size-fits-all strategy on the ground. With genetic testing, we can develop more personalized, more precise approaches that will be much more effective for prevention and early detection of the disease,” he says.

Elkon also places a major focus on teaching ‘predictive genetics’ in his genetics classes for TAU medical students. “Genetic screening will become common practice, similar to routine blood work and other widespread check-ups, and future physicians need to be aware of this. Early detection has a major effect on prognosis and survival,” he explains.

Prof. Elkon works on trying to solve the genetic inequality dilemma, which has surfaced alongside progress in the field. Of all massive genetic breast cancer studies in the world, 90% were conducted on women of European ancestry, making findings and discoveries relevant mostly to this ethnicity. Elkon and his team were able to show that while in Israel the findings translate well to women of Ashkenazi descent, predictive performance substantively declines for individuals of other ethnicities, such as North African, Ethiopian or Druze. Elkon hopes to help come up with computational tools to successfully transfer the findings cross-ethnically. Together with physicians at the Rabin Medical Center (Beilinson Hospital) and the Clalit HMO, he’s heading research on the topic.

“We can turn a person’s skin cell into an undifferentiated stem cell, and from there, into a cell of any organ we want.” – Dr. Ben Maoz

Treatment Personalization

Prevention is the ideal alternative, but what can be done about treatment when disease does occur? On the other side of campus, in his cutting-edge lab at the Susan and Henry Samueli Engineering Building, Dr. Ben Maoz of the Fleischman Faculty of Engineering and the Sagol School of Neuroscience is revolutionizing drug development and treatment personalization.

“The drug development process hasn’t changed in 70 years. It takes a lot of time – about 20 years and $2 billion to develop an FDA-approved medication. And even then, once the drug has been approved, it is not optimal for about 75% of the people taking it, because we all have unique physiologies,” he explains.

Maoz is developing the ‘Organs-on-a-Chip’ technology that circumvents the traditional need for animal drug trials and lets researchers test new medication on something much more similar to humans than rodents—human organ models made of lab-grown cells.

Dr. Ben Maoz and his ‘Organ-on-a-Chip’ model

“It’s a process that takes up to four months overall. We can turn a person’s skin cell into an undifferentiated stem cell, and from there, into a cell of any organ we want,” Maoz explains. Once the researchers have the desired tissue with the specific DNA content they cast it into lego-like units which can be interconnected to mimic the complex physiological system of a specific patient. There is no limit on how many times this can be replicated for multiple trial-and-error runs.

“Parallel trials are especially important when there are multiple treatment options and, without personalized data, we just don’t know which one will work better. In the case of diseases such as cancer, that is crucial information,” he says.

Recently, in a move that exceeded expectations, the FDA approved the Organs-on-a-Chip approach to serve as a complementary tool for drug development, eliminating the unconditional need for animal trials. “This is a major step forward — it opens the door for expediting drug development and making it much more efficient and personalized.”

Maoz’s lab currently collaborates with numerous scientists and hospitals in Israel and the world, as well as three pharmaceutical companies that wish to use the TAU technology to test their drugs for toxicity and efficacy.

While many improvements are still needed, Maoz is certain the technology is here to stay. As for scalability, he says insurance companies will understand that channeling resources into focused, personalized testing and optimal solutions, instead of spending money on ineffective treatments and procedures, is a better and more financially viable strategy. “In the future, patients will arrive, create ‘mini-me’s-on-a-chip’ in fully robotic laboratories, and get an optimal drug for their condition,” Maoz concludes.

Harvesting Stem Cells

Recognizing the increasing demand for cellular material derived from stem cells, and addressing the lack of such facilities in Israel, TAU recently established the Stem Cell Core Lab for Regenerative Medicine, a multidisciplinary initiative of the Faculties of Medicine, Engineering, and The George S. Wise Faculty of Life Sciences; the Sagol Center for Regenerative Medicine; and TAU’s Vice President for R&D.

The lab already serves dozens of research groups across the TAU campus, as well as from other Israeli research institutions and commercial companies. Research based on stem cell technology advances exciting scientific breakthroughs in precision medicine and the Center is there “to help it reach stages of early clinical evaluation.”

Gene Therapy for All

“In gene therapy, the ‘one-size-fits-all’ approach often works and may even be the preferred option,” says Dr. Adi Barzel from the School of Neurobiology, Biochemistry & Biophysics at the George S. Wise Faculty of Life Sciences.

Dr. Adi Barzel (center) with Dr. Erik Shifrut and Dr. Anat Globerson Levin at their lab in the Sourasky Medical Center (Ichilov Hospital).

“The COVID vaccines, several cancer therapy drugs, and therapies for rare diseases, which are all already FDA-approved and used on the market, are examples of generic gene therapies that work for most,” he explains.

“Gene therapy is no longer a dream; it is a reality.” – Dr. Adi Barzel

Barzel’s team works on engineering the cells of the human immune system so that they can better combat cancer, infections, and autoimmune diseases. Last year, in a world first, they succeeded in using the gene-editing technology CRISPR to engineer type-B white blood cells with antibodies to successfully fight the HIV virus.

“For this specific drug it will take another 5 to 6 years before we get to clinical trials — these technologies take time to mature, but gene therapy is no longer a dream, it is a reality,” Barzel states.

Barzel envisions that similar to the COVID vaccine, the HIV medication would need no personal adjustment, and ideally be available “in vials at your neighborhood clinic”, and affordable to all.

He predicts that in 10 years we will see many more treatments based on genome editing, gene therapy, and immunotherapy in the fields of rare diseases, cancer, and cardiovascular diseases. “We will also see many more vaccines based on the wonderful mRNA technology [the tech behind the novel COVID vaccines]. I believe all current vaccines will become mRNA-based. In addition, we will see the development of vaccines against diseases for which we currently have none, such as HIV and different types of cancer. This will take more work, but it is super exciting.”

To significantly boost the development of these therapies and make a real-world impact, Barzel heads his lab’s collaboration with the Tel Aviv Sourasky Medical Center as part of the joint Dotan Center for Advanced Therapies. “This collaboration is crucial for our ability to take our ideas from the bench to the bedside,” he explains. The partnership fast-tracks the process of working with patient samples, allowing the researchers to get efficient results quickly and establishing an atmosphere of cooperation that translates into real progress in the clinic.

By Sveta Raskin

New Treatment Reduces ADHD Symptoms in 1 out of 3 Students

Written by AUFTAU on 13 June 2023. Posted in Newsroom.

Attention Deficit Hyperactivity disorder (ADHD) is one of the most common mental disorders affecting children. Symptoms of ADHD include inattention, hyperactivity, and impulsivity, and the disorder is considered a chronic and debilitating disorder that affects many aspects of an individual’s life, including academic and professional achievements, interpersonal relationships, and daily functioning.

Tel Aviv University has developed a new treatment called Computerized Progressive Attention Training (CPAT), which has shown remarkable efficacy in alleviating symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among students. In fact, a notable 33% of students experienced significant improvements in their symptoms when undergoing CPAT, surpassing the improvement in symptoms of only 11% of the students who participated in a parallel protocol involving mindfulness training. During this mindfulness training, students practiced a specific form of meditation designed to mitigate their attention difficulties. Importantly, the benefits of CPAT also outshone those of drug treatments like Ritalin, as the improvements persisted for up to four months after the completion of the treatment protocol.

Research Challenges with Non-Medication Interventions

The study was the doctoral dissertation of Dr. Pnina Stern, under the guidance of Prof. Lilach Shalev-Mevorach of The Jaime and Joan Constantiner School of Education at Tel Aviv University. The encouraging results of the study were recently accepted for publication in the Journal of Attention Disorders.

“We developed the CPAT system years ago, and it produced good results in previous studies that we conducted, mainly in children,” explains Prof. Shalev-Mevorach. “Furthermore, in the only study that we conducted in adults with ADHD, positive findings were obtained, but without indications of ‘far transfer,’ meaning an improvement in functions for which participants were not directly trained in the treatment.”

According to Prof. Shalev-Mevorach, it is challenging for researchers to make scientific claims about the effectiveness of non-medication treatments because it is difficult to compare them to a “non-medication placebo.” In other words, when studying non-medication treatments, it’s hard to distinguish the effects of the treatment itself from other factors like the attention participants receive during training sessions or the effort they put into the research. This makes it complex to determine the true impact of non-medication interventions.

Prof. Lilach Shalev-Mevorach

Students with ADHD Enrolled

In the current study, the team of researchers tried to resolve this by employing a research design that included two control groups: a regular control group, which performed the various assessment tasks at two points in time without any intervention as part of the research (the passive control group) and a second control group that participated in mindfulness training sessions under the guidance of a professional instructor. This type of training has yielded positive results in previous studies in people with ADHD.

For the experiment 54 students, male and female, diagnosed with ADHD were recruited from Tel Aviv University and other academic institutions. The subjects were blindly divided into three groups: a zero-intervention control group, a mindfulness group and a CPAT group.

Participants in the CPAT and the Mindfulness groups attended two-hour long group meetings on the University campus once a week, where the CPAT group received Computerized Progressive Attention Training and the mindfulness group received training from a certified mindfulness instructor.

Before and after the intervention protocol, the participants of the three groups performed a comprehensive series of assessment tests: standard computerized tests to assess attention functions, behavioral assessment questionnaires (self-reported ADHD symptoms), and mindfulness questionnaires (self-reported feelings such as stress, anxiety and well-being). In addition, a novel measurement was used for this intervention study, whose participants were, as mentioned, higher-education students: they were asked to read a text from a scientific article while their eye movements were tracked by an eye-tracker. The indices produced using the eye-tracking system made it possible to identify a pattern of inattentive reading, which was used as a measure of reading efficiency in an academic context. Finally, the participants filled out a questionnaire regarding their academic difficulties.

Improvements Maintained Over Time

Prof. Shalev-Mevorach says the results were very positive: “We saw improvements in the attention functions themselves, that is, ‘near transfer,’ for example in sustained attention, the ability to remain attentive for a long period of time, and in attention control, the ability to delay a routine response. But the main thing, is that we saw significant improvements in the participants’ daily and academic functioning, such as reduced repeated reading while reading a scientific article. Furthermore, the improvements in these attention functions were connected to the reduction in behavioral symptoms of ADHD and in repetitive reading.”

“In other words, the CPAT trained the attention mechanisms themselves, and their improvement was related to the improvement achieved in behavioral symptoms and reading patterns. 33% of the participants who received the CPAT protocol showed a significant improvement in ADHD symptoms, compared to only 11% of those who underwent the mindfulness protocol. The improvements obtained were preserved in the testing that was carried out about four months after the end of the intervention protocol.”

Prof. Shalev-Mevorach notes that the effects of stimulant drugs (psychostimulants) such as Ritalin and Concerta are ‘on-off’: patients who take Ritalin daily enjoy significant improvements, but when they stop the treatment, the improvements fade, and they return to the starting point. She says the researchers wish to bring about “a profound change in basic attention functions, a change that will be significant in the long term, as an additional option alongside medication, and of course as an alternative to drug treatment in cases in which it isn’t applicable.”

“Hope Is Like the Air We Breathe”

Written by AUFTAU on 11 June 2023. Posted in Newsroom.

The role of hope in supporting mental health.

The role of hope in supporting mental health is not sufficiently understood among relevant professionals, according to Dr. Dorit Redlich Amirav of TAU’s Department of Occupational Therapy, Steyer School of Health Professions, Sackler Faculty of Medicine.

“Hope is similar to the air we breathe,” says Redlich Amirav. “Air is taken for granted in our daily life until we are suffocating and struggling to breathe.”

How Hope Transcends Generations

Redlich Amirav studies how different groups implement hopeful thinking and improve mental well-being through meaningful occupations. Through her findings, she aspires to help mental health professionals to integrate concepts of hope into their research and treatment and, in the long run, provide a longer-lasting and greater impact on each patient’s holistic well-being.

“Hope is similar to the air we breathe. Air is taken for granted in our daily life until we are suffocating and struggling to breathe.” – Dr. Dorit Redlich Amirav

In new research published in Qualitative Health Research, she investigated the cross-generational transmission of hope. Redlich Amirav cites one of her female participants who was forced by her grandfather to quit school in sixth grade. She felt her hope diminish but stated that her hopeless personal circumstances led her to put more of an emphasis on the importance of education and studying with her own two daughters who both graduated from university.

Other participants displayed this particular kind of cross-generational hope. For example, a mother told Redlich Amirav about her father, who was a violinist until the Nazis broke his fingers. The mother internalized this trauma in a negative way, but all four of her own children play instruments and one of them is an opera singer. She inadvertently conveyed how hope and music are intertwined for them and their heritage.

Hope as a Key to Pandemic Adaptation

In 2019, Redlich Amirav was appointed director of the Israeli chapter of the International Hope Barometer. She says that it came just in time: hope became a key factor in successfully adapting to the trials and tribulations of the pandemic. During the lockdowns, she says that people found meaning in new ways of interacting; specific trends point to the importance of goal-directed behavior in increasing hope.

The Power of Sleep

Written by AUFTAU on 7 June 2023. Posted in Newsroom.

While a good night’s sleep is known to be critical for the consolidation of long-lasting memories, so far there has been little evidence regarding the precise processes at work during human sleep. A breakthrough study demonstrated for the first time that long-lasting memories are consolidated in the human brain through communication between the hippocampus and the cerebral cortex during sleep. Moreover, the researchers found that by inducing deep-brain stimulation during sleep they can improve memory consolidation. They believe intervention during sleep represents a unique approach that can be further developed in the future to provide hope for people with memory impairments such as dementia.

Enhancing Memory Consolidation During Sleep

The unique study, which was published in the leading journal Nature Neuroscience, involved an international collaboration led by Dr. Maya Geva-Sagiv (today at UC Davis). The study was a collaboration between the laboratories of Prof. Yuval Nir from the Sackler Faculty of Medicine, Department of Biomedical Engineering at The Iby and Aladar Fleischman Faculty of Engineering, and Sagol School of Neuroscience at Tel Aviv University, and Prof. Itzhak Fried from the Department of Neurosurgery at UCLA and the Sackler Faculty of Medicine at Tel Aviv University.

“Intervention during sleep represents a unique approach that can be further developed in the future to provide hope for people with memory impairments such as dementia.” – Prof. Yuval Nir

The researchers (from left to right): Dr. Maya Geva-Sagiv, Prof. Yuval Nir and Prof. Itzhak Fried

“This study was made possible by a rare group of 18 patients with epilepsy at the UCLA Medical Center,” says Prof. Nir. “Prof. Fried implanted electrodes in these patients’ brains to try and pinpoint the areas that cause their epileptic seizures, and they volunteered to take part in a study investigating the effects of deep-brain stimulation during sleep. Close work with expert neurologists led by Prof. Dawn Eliashiv at UCLA enabled our team to integrate advanced brain stimulation in the research. Thus, we were able to test, for the first time in humans, the long-held hypothesis – that coordinated activity of the hippocampus and cerebral cortex during sleep is a critical mechanism in consolidating memories.”

“Moreover, we improved memory consolidation through a special stimulation protocol that enhanced synchronization between these two areas in the brain. Intervention during sleep represents a unique approach that can be further developed in the future to provide hope for people with memory impairments such as dementia.”

“In this study we directly examined the role of neural activity and electrical brain waves during sleep. Our goal was to enhance the natural mechanisms at play, to discover exactly how sleep assists in stabilizing memories.” – Dr. Maya Geva-Sagiv

Unraveling Mechanism

“We know that a good night’s sleep is critical for the consolidation of long-lasting memories, but so far, we had little evidence regarding the precise processes that are at work during human sleep,” explains Dr. Maya Geva-Sagiv. “In this study we directly examined the role of neural activity and electrical brain waves during sleep. Our goal was to enhance the natural mechanisms at play, to discover exactly how sleep assists in stabilizing memories.”

The researchers developed a deep-brain stimulation system that improves electrical communication between the hippocampus – a deep-brain region involved in acquiring new memories, and the frontal cortex – where memories are stored for the long term. By monitoring activity in the hippocampus during sleep, the system enables precisely timed delivery of electrical stimulation to the frontal cortex.

The study’s participants completed two memory tests, and their performance was compared after two different nights – one undisturbed and one with deep-brain stimulation. On both occasions, they were asked in the morning to recognize famous persons whose pictures they had been shown the previous evening. The study found that deep-brain stimulation significantly improved the accuracy of their memory.

“To our surprise, we also discovered that the intervention did not significantly increase the number of right answers given by participants, but rather reduced the number of wrong answers. This suggests that sleep sharpens the accuracy of our memory…” – Prof. Yuval Nir

Sharpening Memory Accuracy

“We found that our method had a beneficial effect on both brain activity during sleep and memory performance,” says Prof. Fried. “All patients who had received synchronized stimuli to the frontal cortex demonstrated better memory performance, compared to nights of undisturbed sleep. The control group, which received similar yet unsynchronized stimuli, showed no memory improvement. Our deep-brain stimulation method is unique because it is close-looped – stimuli are precisely synchronized with hippocampal activity. In addition, we monitored the stimuli’s impact on brain activity at a resolution of individual neurons.”

“Our findings support the hypothesis that precise coordination between sleep waves assists communication between the hippocampus that takes in new memories, and the frontal cortex that stores them for the long term,” adds Prof. Nir.

“To our surprise, we also discovered that the intervention did not significantly increase the number of right answers given by participants, but rather reduced the number of wrong answers. This suggests that sleep sharpens the accuracy of our memory, or in other words, it removes various distractions from the relevant memory trace.”

The study was supported by grants from the US National Institutes of Health (NIH), the European Research Council (ERC), the US National Science Foundation (NSF), the US-Israel Bilateral Science Foundation (BSF), and the Human Frontier Science Program (HFSP). The paper’s other co-authors are: Prof. Dawn Eliashiv, Dr. Emily Mankin, Natalie Cherry, Guldamla Kalender, and Dr. Natalia Tchemondanov of UCLA, and Dr. Shdema Epstein from Tel Aviv University.

Prof. Yosef Shiloh Elected as International Member of US National Academy of Sciences

Written by AUFTAU on 18 May 2023. Posted in Newsroom.

Professor Emeritus Yosef Shiloh from TAU’s Sackler Faculty of Medicine was elected an international member of the US National Academy of Sciences (NAS). The Academy includes approximately 2,500 American scientists from all fields of science and another approximately 500 foreign scientists from all over the world. Prof. Shiloh is the 43rd Israeli researcher elected to NAS, alongside Nobel laureates Prof. Ada Yonath, Prof. Dan Shechtman and Prof. Aaron Ciechanover. Prof. Shiloh is the Incumbent of the David and Inez Myers Chair for Cancer Genetics in the Department of Human Molecular Genetics and Biochemistry in the Sackler Faculty of Medicine at Tel Aviv University.

Prof. Shiloh received the exciting news while attending a conference in Boston. He has been the recipient of the EMET Prize, the Israel Prize, and the Clowes Award for Outstanding Cancer Research – the most important prize awarded by the American Association for Cancer Research, which has thousands of cancer researchers as members. Being elected to the Academy is a particular honor, as it reflects widespread recognition by all the members of the Academy, from a variety of scientific fields. The acceptance bar for non-American members is particularly high, adding to the prestige of “international” members.

The US National Academy of Sciences advises the American government and nation on matters of science, engineering and medicine, based on a charter granted to it by Congress and signed by President Abraham Lincoln in 1863. Membership in the Academy is lifelong, and up to 120 scientists from the USA and up to 30 foreign scientists are elected to the Academy each year.

Prof. Shiloh: “It is a great honor and I thank the Academy members for recognizing our work. NAS is a body whose opinion is heard and given consideration and I hope that the opinion of the Israeli Academy of Sciences and Humanities, of which I am a member, will be heard here in a similar way. In the US, the president, the administration and the public listen to what the Academy says, and hence the weight that the Americans attribute to membership in this institution.”

Prof. Karen Avraham, Dean of the Sackler Faculty of Medicine:” This is a tremendous honor for us in the Department and the Faculty of Medicine at Tel Aviv University. Prof Yosef Shiloh’s research has made a seminal and remarkable contribution in the area of a rare but devastating genetic disease, ataxia-telangiectasia (A-T), with far-reaching implications for DNA repair and cancer. Most compelling, what drove Prof. Shiloh every step of the way was his compassion for the patients. The main theme of his work can be summarized in the title of a lecture that he has delivered to numerous audiences over the years: “Investigation of Rare Genetic Disorders: A Mission for Human Welfare and a Steppingstone in Understanding our Biology”. Prof. Shiloh continues to explore the connection between A-T, neurodegeneration and aging in search of new treatment modalities for A-T, as well as to devote his efforts to educating the public about the medical and social implications of the genome revolution.”

Next year Prof. Shiloh will participate in a ceremony in honor of the members selected this year, which will be held at the Academy House in Washington, DC.

Tel Aviv University Researchers Present New Treatment for Ovarian Cancer

Written by AUFTAU on 30 April 2023. Posted in Newsroom.

Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. In a study conducted at Tel Aviv University researchers used protein CKAP5 (cytoskeleton-associated protein) for the first time as a therapeutic target for RNA-based nanodrugs. After identifying a genetically unstable mutation resistant to both chemotherapy and immunotherapy in the tissues of ovarian cancer, the researchers targeted these cells with lipid nanoparticles containing RNA for silencing CKAP5 – causing the cells to collapse and achieving an 80% survival rate in animal models.

“The lipid nanoparticles developed by Prof. Peer enabled us for the first time to silence [the CKAP5] protein through targeted delivery of an RNA drug. We proved that CKAP5, a protein responsible for the cell’s stability, can be silenced, and that this procedure collapses and destroys the entire cancer cell.” – Dr. Sushmita Chatterjee

Targeted Delivery of RNA Drug

The breakthrough was achieved by a TAU research team led by Prof. Dan Peer of The Shmunis School of Biomedicine and Cancer Research, a global pioneer in the development of RNA-based drugs, Head of the Laboratory of Precision Nanomedicine, and TAU’s VP for R&D; and by Dr. Sushmita Chatterjee, post-doctoral student from India at Prof. Peer’s lab, in collaboration with Prof. David Sprinzak of The George S. Wise Faculty of Life Sciences and Prof. Ronen Zaidel-Bar of the Sackler Faculty of Medicine. The study was funded by the Rivkin Foundation for Ovarian Cancer Research and the Shmunis Family Foundation. The results were published in the leading scientific journal Science Advances.

“The protein CKAP5 has never been studied with relation to the fight against cancer, simply because there was no known way to silence it,” explains Dr. Chatterjee. “The lipid nanoparticles developed by Prof. Peer enabled us for the first time to silence this protein through targeted delivery of an RNA drug. We proved that CKAP5, a protein responsible for the cell’s stability, can be silenced, and that this procedure collapses and destroys the entire cancer cell.”

Prof. Dan Peer

“Something Like a Dominoes Game”

At the second stage of the study the researchers tested the new CKAP5-silencing RNA drug on 20 types of cancer. Some cancer cells proved more sensitive than others to this procedure. Cancers displaying high genetic instability, which are usually highly resistant to chemotherapy, were found to be especially sensitive to the silencing of CKAP5.

“As researchers, we are involved in something like a dominoes game: we always look for the one piece in the cancer’s structure that is so important, that if we pull it out the entire cell will collapse. CKAP5 is such a domino piece, and we are already working on more applications (…)” – Prof. Dan Peer

“All cancer cells are genetically unstable,” says Dr. Chatterjee. “Otherwise, they would be healthy, not cancerous. However, there are different levels of genetic instability. We found that cancer cells that are more unstable, are also more affected by damage to CKAP5. Our drug pushed them to their limit, and essentially destroyed their structure. Our idea was to turn the trait of genetic instability into a threat for these cells, by using RNA to silence the flawed protein. We demonstrated for the first time that CKAP5 can be used to kill cancer cells, and then observed the biological mechanism that causes the cancer cells to collapse in the protein’s absence.”

Equipped with these insights, the researchers tested the new drug in an animal model for ovarian cancer, achieving a survival rate of 80%.

“We chose ovarian cancer because it’s a good target,” explains Prof. Peer. “While highly resistant to both chemotherapy and immunotherapy, this type of cancer is very sensitive to the silencing of CKAP5. It should be emphasized that the CKAP5 protein is a new target in the fight against cancer. Targeting cell division is not new, but using RNA to target proteins that make up the cell’s skeleton (cytoskeleton) – this is a new approach and a new target that must be further investigated. As researchers, we are involved in something like a dominoes game: we always look for the one piece in the cancer’s structure that is so important, that if we pull it out the entire cell will collapse. CKAP5 is such a domino piece, and we are already working on more applications, this time in blood cancers.”

“Family Smoking” on The Porch

Written by AUFTAU on 16 April 2023. Posted in Newsroom.

Many parents think that they are protecting their children by smoking on the porch or next to the window in a room. However, a new study by Tel Aviv University finds that, in contrast to such beliefs, restricting smoking to the porch does not protect most children from exposure to tobacco smoke. The research team tested for the presence of nicotine in the hair of children whose parents restrict their smoking to the porch or outside the house. Their findings are worrisome: nicotine was found in the hair of six out of ten children.

The researchers emphasize that “in Israel, home porches should be regarded as part of the environment of the home. Smoking next to a window or in another specific place in the home does not protect most children from exposure. Our recommendations are unequivocal: to reduce children’s exposure to tobacco smoke, smoking should be entirely avoided within a range of ten meters from the house. Likewise, in open areas, smokers should maintain a distance of at least ten meters from the children.”

“The Israeli situation is of great concern because in many cases, porches in Israel are directly adjacent to the living areas and may even be partially open some of the time (…) The parents mistakenly believe that the porch offers a ‘safe’ place to smoke.” Prof. Leah (Laura) Rosen

The Porch is No ‘Safe’ Place

The study was led by Prof. Leah (Laura) Rosen from the School of Public Health in Sackler Faculty of Medicine, Tel Aviv University. Also participating in the study: Prof. David Zucker from the Department of Statistics and Data Science, Hebrew University, Jerusalem; Dr. Shannon Gravely from the Department of Psychology, Waterloo University, Canada; Dr. Michal Bitan from the Computer Science Department, the College of Management; Dr. Ana Rule from the Department of Health and Environmental Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore; and Dr. Vicki Meyers from the Gertner Institute for Epidemiology and Public Policy Research, Sheba Medical Center. The study was published in the International Journal of Environmental Research and Public Health.

In the first stage of the study (published about two years ago), the research team studied hair samples of the children of smoking parents for the presence of nicotine. This provides an estimate of their exposure to tobacco smoke over the past months. It was found that 70% of the children of smoking parents had measurable hair nicotine.

In the current stage of the study, the researchers examined the data by the location of parental smoking. Analysis of the data showed that in families in which the parents restricted their smoking to the porch or outdoors, 62% of the children were still exposed to tobacco smoke.

Prof. Leah (Laura) Rosen

“It is known that smoking outside the house, even when the doors and windows are fully closed, does not completely protect children from exposure to tobacco smoke,” says Prof. Rosen. “The Israeli situation is of great concern because in many cases, porches in Israel are directly adjacent to the living areas and may even be partially open some of the time. The proximity allows smoke to drift from those areas to the interior of the house. The parents mistakenly believe that the porch offers a ‘safe’ place to smoke.”

“In fact, the children are likely to be directly exposed when they come out to the porch and someone is smoking, or when smoke drifts into the house. Once in the home, the smoke is absorbed into the environment, for example, into the furniture or walls or rugs, and is then gradually discharged into the air over weeks or months.”

“Further, this residual smoke, known as third hand smoke, can be absorbed into the body from the environment via swallowing or through the skin, especially among infants and small children. In addition, smoking parents transmit the toxins from the tobacco smoke on their skin, on their hands, in their hair, on their clothing. Therefore, it is recommended to brush teeth, wash hands, and change clothes after smoking, before contact with children.”

“85% of tobacco smoke is invisible, and our sense of smell is not reliable, so many parents mistakenly believe that they are protecting their children, while in fact they are exposing them to substantial health risks.” Prof. Leah (Laura) Rosen

Plea to Israel’s Health Ministry

Prof. Rosen notes that this new information is directly relevant to Case 1416/21 on neighbor smoking, currently being heard in the Supreme Court. The appeal against the Ministries of the Environment, Health, and Interior concerns the tobacco smoke that penetrates apartments as an environmental hazard, a claim that is supported by the definition of an environmental hazard in the Clean Air Law, the Hazard Prevention Law, and the Penal Code.

Prof. Rosen: “The results of this study show that among smoking families, restricting smoking to the porch does not protect most children from exposure to tobacco smoke. Therefore, the Health Ministry’s approach, which opposes protection for individuals from smoke incursion into their own homes to protect the smokers’ children, does not protect the children of smokers, and in addition it can cause substantial harm to neighbors and the children of neighbors. We ask the Health Ministry to reconsider its stand in light of these findings.”

“The State of Israel must make the reduction of parental smoking a national goal and invest the appropriate resources in this issue. Unfortunately, there are many misconceptions regarding when and how the exposure occurs. 85% of tobacco smoke is invisible, and our sense of smell is not reliable, so many parents mistakenly believe that they are protecting their children, while in fact they are exposing them to substantial health risks. As a society, we must safeguard citizens and distance everyone from the risks of tobacco smoke exposure, especially infants and children, pregnant women, and all vulnerable populations,” concludes Prof. Rosen.

Tiny Robot Navigates in Physiological Environment and Captures Targeted Damaged Cells

Written by AUFTAU on 28 March 2023. Posted in Newsroom.

Researchers at Tel Aviv University have developed a hybrid micro-robot, the size of a single biological cell (about 10 microns across), that can be controlled and navigated using two different mechanisms – electric and magnetic. The micro-robot is able to navigate between different cells in a biological sample, distinguish between different types of cells, identify whether they are healthy or dying, and then transport the desired cell for further study, such as genetic analysis. The micro-robot can also transfect a drug and/or gene into the captured targeted single cell. According to the researchers, the development may help promote research in the important field of ‘single cell analysis’, as well as find use in medical diagnosis, drug transport and screening, surgery, and environmental protection.

Inspired by Biological Micro-swimmers

The innovative technology was developed by Prof. Gilad Yossifon from the School of Mechanical Engineering and Department of Biomedical Engineering at Tel Aviv University and his team: post-doctoral researcher Dr. Yue Wu and student Sivan Yakov, in collaboration with Dr. Afu Fu, Post-doctoral researcher, from the Technion, Israel Institute of Technology. The research was published in the journal Advanced Science.

“Developing the micro-robot’s ability to move autonomously was inspired by biological micro-swimmers, such as bacteria and sperm cells. This is an innovative area of research that is developing rapidly, with a wide variety of uses in fields such as medicine and the environment, as well as a research tool.” – Prof. Gilad Yossifon

Prof. Gilad Yossifon explains that micro-robots (sometimes called micro-motors or active particles) are tiny synthetic particles the size of a biological cell, which can move from place to place and perform various actions (for example: collection of synthetic or biological cargo) autonomously or through external control by an operator. According to Prof. Yossifon, “developing the micro-robot’s ability to move autonomously was inspired by biological micro-swimmers, such as bacteria and sperm cells. This is an innovative area of research that is developing rapidly, with a wide variety of uses in fields such as medicine and the environment, as well as a research tool”.

WATCH: The Hybrid Micro-Robot

As a demonstration of the capabilities of the micro-robot the researchers used it to capture single blood and cancer cells and a single bacterium, and showed that it is able to distinguish between cells with different levels of viability, such as a healthy cell, a cell damaged by a drug, or a cell that is dying or dying in a natural ‘suicide’ process (such a distinction may be significant, for example, when developing anti-cancer drugs).

After identifying the desired cell, the micro-robot captured it and moved the cell to where it could be further analyzed. Another important innovation is the ability of the micro-robot to identify target cells that are not labeled – the micro-robot identifies the type of cell and its condition (such as degree of health) using a built-in sensing mechanism based on the cell’s unique electrical properties.

Effective in Physiological Environments

“Our new development significantly advances the technology in two main aspects: hybrid propulsion and navigation by two different mechanisms – electric and magnetic,” explains Prof. Yossifon. “In addition, the micro-robot has an improved ability to identify and capture a single cell, without the need for tagging, for local testing or retrieval and transport to an external instrument. This research was carried out on biological samples in the laboratory for in-vitro assays, but the intention is to develop in the future micro-robots that will also work inside the body – for example, as effective drug carriers that can be precisely guided to the target”.

“… the technology will support the following areas: medical diagnosis at the single cell level, introducing drugs or genes into cells, genetic editing, carrying drugs to their destination inside the body, cleaning the environment from polluting particles, drug development, and creating a ‘laboratory on a particle’ – a microscopic laboratory designed to carry out diagnostics in places accessible only to micro-particles.” – Prof. Gilad Yossifon

The researchers explain that the hybrid propulsion mechanism of the micro-robot is of particular importance in physiological environments, such as found in liquid biopsies: “The micro-robots that have operated until now based on an electrical guiding mechanism were not effective in certain environments characterized by relatively high electrical conductivity, such as a physiological environment, where the electric drive is less effective. This is where the complementary magnetic mechanism come into play, which is very effective regardless of the electrical conductivity of the environment”.

Prof. Yossifon concludes: “In our research we developed an innovative micro-robot with important capabilities that significantly contribute to the field: hybrid propulsion and navigation through a combination of electric and magnetic fields, as well as the ability to identify, capture, and transport a single cell from place to place in a physiological environment. These capabilities are relevant for a wide variety of applications as well as for research. Among other things, the technology will support the following areas: medical diagnosis at the single cell level, introducing drugs or genes into cells, genetic editing, carrying drugs to their destination inside the body, cleaning the environment from polluting particles, drug development, and creating a ‘laboratory on a particle’ – a microscopic laboratory designed to carry out diagnostics in places accessible only to micro-particles.”