Tag: Medicine

In First, Aging Stopped in Humans: TAU Co-Study

Written by AUFTAU on 24 November 2020. Posted in Newsroom.

A first-of-its-kind clinical trial in human subjects: A new study from Tel Aviv University and the Shamir Medical Center indicates that HBOT (treatments with high-pressure oxygen) in healthy aging adults can stop the aging of blood cells.

The researchers found that a unique protocol of treatments in a pressure chamber can reverse two major processes associated with aging and its illnesses: the shortening of telomeres – – protective regions located at both ends of every chromosome (the chromosomes contain the genetic material in the cell’s nucleus), and the accumulation of senescent (old and malfunctioning) cells in the body. Focusing on immune cells containing DNA, obtained from the participants’ blood, the study discovered a significant lengthening – up to 38% – of the telomeres, as well as a decrease of up to 37% in the presence of senescent cells.

The study was led by Prof. Shai Efrati, faculty member of the Sackler School of Medicine and the Sagol School of Neuroscience at Tel Aviv University and Founder and Director of the Sagol Center of Hyperbaric Medicine at the Shamir Medical Center, and Dr. Amir Hadanny, Chief Medical Research Officer of the Sagol Center for Hyperbaric Medicine and Research at the Shamir Medical Center. The clinical trial was conducted as part of a comprehensive Israeli research program that targets aging as a reversible disease. The paper was published in the scientific journal Aging in November 2020.

Prof. Efrati explains: “For many years our team has been engaged in hyperbaric research and therapy – treatments based on protocols of exposure to high-pressure oxygen at various concentrations inside a pressure chamber. Our achievements over the years included the improvement of brain functions damaged by age, stroke or brain injury. In the current study we wished to examine the impact of HBOT on healthy and independent aging adults, and to discover whether such treatments can slow down, stop or even reverse the normal aging process at the cellular level.”

The researchers exposed 35 healthy individuals aged 64 or over to a series of 60 hyperbaric sessions over a period of 90 days. Each participant provided blood samples at four different points in time – before, during, at the end and after the series of treatments, and the researchers analyzed various immune cells (cells containing DNA) in the blood and compared the results.

The findings indicated that the treatments actually reversed the aging process in two of its major aspects: The telomeres at the ends of the chromosomes grew longer instead of shorter, at a rate of 20%-38% for the different cell types; and the percentage of senescent cells in the overall cell population was reduced significantly – by 11%-37% depending on cell type.

Prof. Efrati: “Today telomere shortening is considered the ‘Holy Grail’ of the biology of aging. Researchers around the world are trying to develop pharmacological and environmental interventions that enable telomere elongation. Our HBOT protocol was able to achieve this, proving that the aging process can in fact be reversed at the basic cellular-molecular level.”

Dr. Hadanny: “Until now, interventions such as lifestyle modifications and intense exercise were shown to have some inhibiting effect on telomere shortening. But in our study, only three months of HBOT were able to elongate telomeres at rates far beyond any currently available interventions or lifestyle modifications. With this pioneering study, we have opened a door for further research on the cellular impact of HBOT and its potential for reversing the aging process.”

TAU developed genome editing system destroys cancer cells

Written by AUFTAU on 20 November 2020. Posted in Newsroom.

Researchers at Tel Aviv University have demonstrated that the CRISPR/Cas9 system is very effective in treating metastatic cancers, a significant step on the way to finding a cure for cancer. The researchers developed a novel lipid nanoparticle-based delivery system that specifically targets cancer cells and destroys them by genetic manipulation. The system, called CRISPR-LNPs, carries a genetic messenger (messenger RNA), which encodes for the CRISPR enzyme Cas9 that acts as molecular scissors that cut the cells’ DNA.

The revolutionary work was conducted in the laboratory of Prof. Dan Peer, VP for R&D and Head of the Laboratory of Precision Nanomedicine at the Shmunis School of Biomedicine and Cancer Research at TAU. The research was conducted by Dr. Daniel Rosenblum together with Ph.D. student Anna Gutkin and colleagues at Prof. Peer’s laboratory, in collaboration with Dr. Dinorah Friedmann-Morvinski from the School of Neurobiology, Biochemistry & Biophysics at TAU; Dr. Zvi R. Cohen, Director of the Neurosurgical Oncology Unit and Vice-Chair of the Department of Neurosurgery at the Sheba Medical Center; Dr. Mark A. Behlke, Chief Scientific Officer at IDT Inc. and his team; and Prof. Judy Lieberman of Boston Children’s Hospital and Harvard Medical School.

The results of the groundbreaking study, which was funded by ICRF (Israel Cancer Research Fund), were published in November 2020 in Science Advances.

“This is the first study in the world to prove that the CRISPR genome editing system can be used to treat cancer effectively in a living animal,” said Prof. Peer. “It must be emphasized that this is not chemotherapy. There are no side effects, and a cancer cell treated in this way will never become active again. The molecular scissors of Cas9 cut the cancer cell’s DNA, thereby neutralizing it and permanently preventing replication.”

To examine the feasibility of using the technology to treat cancer, Prof. Peer and his team chose two of the deadliest cancers: glioblastoma and metastatic ovarian cancer. Glioblastoma is the most aggressive type of brain cancer, with a life expectancy of 15 months after diagnosis and a five-year survival rate of only 3%. The researchers demonstrated that a single treatment with CRISPR-LNPs doubled the average life expectancy of mice with glioblastoma tumors, improving their overall survival rate by about 30%. Ovarian cancer is a major cause of death among women and the most lethal cancer of the female reproductive system. Most patients are diagnosed at an advanced stage of the disease when metastases have already spread throughout the body. Despite progress in recent years, only a third of the patients survive this disease. Treatment with CRISPR-LNPs in a metastatic ovarian cancer mice model increased their overall survival rate by 80%.

“The CRISPR genome editing technology, capable of identifying and altering any genetic segment, has revolutionized our ability to disrupt, repair or even replace genes in a personalized manner,” said Prof. Peer. “Despite its extensive use in research, clinical implementation is still in its infancy because an effective delivery system is needed to safely and accurately deliver the CRISPR to its target cells. The delivery system we developed targets the DNA responsible for the cancer cells’ survival. This is an innovative treatment for aggressive cancers that have no effective treatments today.”

The researchers note that by demonstrating its potential in treating two aggressive cancers, the technology opens numerous new possibilities for treating other types of cancer as well as rare genetic diseases and chronic viral diseases such as AIDS.

“We now intend to go on to experiments with blood cancers that are very interesting genetically, as well as genetic diseases such as Duchenne muscular dystrophy,” says Prof. Peer. “It will probably take some time before the new treatment can be used in humans, but we are optimistic. The whole scene of molecular drugs that utilize messenger RNA (genetic messengers) is thriving – in fact, most COVID-19 vaccines currently under development are based on this principle. When we first spoke of treatments with mRNA twelve years ago, people thought it was science fiction. I believe that in the near future, we will see many personalized treatments based on genetic messengers – for both cancer and genetic diseases. Through Ramot, the Technology Transfer Company of TAU, we are already negotiating with international corporations and foundations, aiming to bring the benefits of genetic editing to human patients.”

Featured image: Prof. Dan Peer

TAU Co-Study: “Green Revolution” Decreased Infant Mortality

Written by AUFTAU on 17 November 2020. Posted in Newsroom.

In the first global-scale study of its kind, researchers used wide-scale data to correlate between the “Green Revolution” in agriculture and the dramatic reduction in infant mortality in the developing world. The Green Revolution was a global effort to increase the global crop yield during the second half of the twentieth century.

“In our study, we sought to use empirical methods based on our hypothesis that larger crop larger yields could improve the level of nutrition of pregnant women and young children, and also increase household income, thus contributing indirectly to improved health,” explained Dr. Fishman, of the TAU Department of Public Policy and the Boris Mints Institute for Strategic Policy Solutions to Global Challenges, who contributed to the research. “During the Green Revolution, there was support for international public agricultural R&D with a focus on developing higher-yielding strains of common staple crops, such as wheat, rice, and corn. By the end of the 20th century, approximately 60% of the developing world’s agricultural lands were using these varieties.”

At the same time, between 1960 and 2000, there was a dramatic improvement in health in the developing world- the percentage of children who died before the age of one was reduced from 20% to 10%. The cause of this improvement has been long-contested and attributed to various public health improvements but the contribution of individual factors, including the impacts of the Green Revolution, has been poorly quantified until now.

The correlation in the study suggests that the Green Revolution was responsible for a decline of some 2.5- 5% in the rate of infant mortality. This represents between 25% to 50% of the overall reduction of infant mortality during that time period.

To conduct the study, the researchers collected detailed data about the mortality rates of 600,000 infants born in 37 developing countries between 1961 and 2000, and cross-referenced them with information about the diffusion of the improved Green Revolution seeds in the place and year of birth of each of these infants. Using sophisticated statistical methods, they estimated the association between these two variables. The analysis found a statistically significant causal link between the two data sets. In locations where improved varieties diffused earlier – in part because of the types of crops grown, there was also a more rapid decrease in mortality rates.

“Our study proves the historical importance of agricultural R&D for the health of the rural populations in the developing world. We showed that improved crop varieties, which thus improved nutrition and income and reduced hunger, saved the lives of tens of millions of children in the second half of the twentieth century, and have most likely also brought about improved health for tens of millions of other individuals not directly visible in the data,” said Dr. Fishman.

According to Dr. Fishman, these findings highlight the continued need to address public health. “Israel, as a global leader in agriculture R&D, has much to offer to the developing world,” he says.

The study was conducted by an international team of researchers from Tel Aviv University, the Indian School of Business, the World Bank, the University of California San Diego, Michigan State University, and Colorado State University. The paper was published in the Journal of Health Economics.

Featured images: TAU Prof. Ram Fishman and agricultural expert Omar Zaidan explain seedling use to farmers in India. Credit: the Nitzan Lab

Study: Women Suffer More from COVID-related Orofacial Pain

Written by AUFTAU on 13 November 2020. Posted in Newsroom.

A new study from the Goldschleger School of Dental Medicine at Tel Aviv University’s Sackler Faculty of Medicine found that during Israel’s first lockdown the general population exhibited a considerable rise in orofacial pain, as well as jaw-clenching in the daytime and teeth-grinding at night – physical symptoms often caused by stress and anxiety. The study was led by Dr. Alona Emodi-Perlman and Prof. Ilana Eli of TAU’s School of Dental Medicine, in collaboration with Dr. Nir Uziel and Dr. Efrat Gilon of TAU, and researchers from the University of Wroclaw in Poland, who examined the Polish population’s reaction to the pandemic. The paper was published in the Journal of Clinical Medicine in October 2020.

Researchers Dr. Emodi-Perlman and Prof. Eli specialize in facial and jaw pain, with emphasis on TMD (Temporo-Mandibular Disorders) – chronic pain in the facial muscles and jaw joints, as well as Bruxism – excessive teeth-grinding and/or jaw-clenching, which can significantly damage the teeth and jaw joints. These syndromes are known to be greatly impacted by emotional factors such as stress and anxiety.

Accordingly, the researchers decided to conduct a study examining the presence and possible worsening of these symptoms in the general population during the first COVID-19 lockdown, due to the national emergency and rise in anxiety levels. The questionnaire was answered by a total of 1,800 respondents in Israel and Poland.

In Israel, a significant rise was found in all symptoms, compared to data from studies conducted before the pandemic:

In Israel’s general population: The prevalence of TMD symptoms rose from about 35% in the past to 47% (increase of 12%) during the pandemic; the prevalence of jaw-clenching in the daytime rose from about 17% to 32% (increase of 15%); and teeth-grinding at night rose from about 10% to 36% (increase of 25%). Altogether a rise of 10%-25% was recorded in these symptoms, which often reflect emotional stress. People who had suffered from these symptoms before the pandemic exhibited a rise of about 15% in their severity.
The researchers found a high correlation between the symptoms on the one hand and gender and anxiety level on the other: Women suffer from these symptoms much more than men, and people with high levels of anxiety tend to develop them more than those with lower anxiety levels.
Dividing the respondents into age-groups also generated interesting results, with the middle group (35-55) reporting a much greater rise in symptoms compared to the younger (18-34) and older (56 and over) groups. At the bottom line, the group that suffered most from the symptoms during the first lockdown were women aged 35-55: 48% suffered from TMD, 46% clenched their jaws in the daytime, and about 50% ground their teeth at night.

In addition, comparing findings in Israel to results in Poland, the researchers found that probability of TMD and Bruxism was much higher among respondents in Poland.

Dr. Emodi-Perlman and Prof. Eli conclude: “Our study, conducted during the first lockdown of the COVID-19 pandemic, found a significant rise in the symptoms of jaw and facial pain, jaw-clenching and teeth-grinding – well-known manifestations of anxiety and emotional distress. We found that women are more likely than men to suffer from these symptoms, and that the 35-55 age group suffered more than the younger (18-34) and older (56 and over) groups. We believe that our findings reflect the distress felt by the middle generation, who were cooped up at home with young children, without the usual help from grandparents, while also worrying about their elderly parents, facing financial problems and often required to work from home under trying conditions.”

TAU Researchers Discover Antibody Combo that Fights COVID-19

Written by AUFTAU on 13 October 2020. Posted in Newsroom.

Researchers at Tel Aviv University identified a combination of COVID-19 antibodies that can serve as both medication for patients and preventive treatment for high-risk populations. The antibody cocktail will be tested in clinical trials over the next few months. Similarly, TAU has submitted a patent application for the antibodies discovered by the researchers.

The scientific breakthrough was achieved by Dr. Natalia Freund and PhD student Michael Mor at the Laboratory of Human Antibody Research at TAU’s Sackler Faculty of Medicine. The results of the study are under revision in the PLOS Pathogens journal.

PhD student Michael Mor

Another important find in the study was that asymptomatic COVID-19 sufferers or those who had mild symptoms developed a weaker antibody reaction, and therefore may contract the disease again. By contrast, all severely ill patients analyzed in the study developed neutralizing antibodies that are likely to protect them from reinfection.

Dr. Freund and her team sequenced thousands of antibodies produced in the bodies of Israeli COVID-19 patients. The researchers were able to isolate and characterize six antibodies derived from the blood of two severely ill patients. They then proved that combinations of three antibodies at a time are effective against COVID-19, providing natural immunity. The researchers found that the blood’s capacity for neutralizing the virus comes from several types of antibodies that simultaneously attack the virus, and the mix neutralizes the COVID-19 virus.

“Since the antibodies are natural and remain stable in the blood, one injection can protect against COVID-19 for several weeks, or even several months,” says Freund. “Our vision is that in the future, the cocktail will be used to treat COVID-19 patients – like the experimental cocktail administered to U.S. President Trump, or as a preventive measure for high-risk populations and medical personnel – until the much-awaited vaccine finally arrives. This cocktail was developed naturally by the patients’ immune systems, which means that it is probably safe for use,” say the researchers.

The team

In the second stage of the project, the researchers tried to isolate specific antibodies that stop the virus from binding to the human cell and replicating itself inside the cell. They identified six different antibodies, obtained from two severely ill participants, and proved that these antibodies are effective in both treating and preventing infection in cell cultures.

The research began in April 2020, soon after the pandemic reached Israel. Dr. Freund and her team studied 18 of Israel’s earliest COVID-19 patients. “One question we asked was whether there was any difference between mild and severe cases – with regard to both the quality and quantity of the anti-viral antibodies produced by the immune system. We found a significant statistical difference between the two groups of patients in the ability of their antibodies to neutralize COVID-19: Only a small portion of the mildly ill participants developed neutralizing antibodies, and some developed no antibodies whatsoever. Thus, we may assume that people who were infected but remained asymptomatic or developed very mild symptoms, may possibly contract the disease a second time. The blood of all severely ill patients, on the other hand, contained neutralizing antibodies that will probably protect them from reinfection.”

Many experts took part in the project: participating patients were recruited with the help of Dr. David Hagin, Director of Allergy and Immunology at the Tel Aviv Sourasky (Ichilov) Medical Center and Dr. Oren Zimhony, Head of Infectious Diseases at the Kaplan Medical Center. Genetic sequencing of immune cells was conducted in collaboration with the Israeli startup immunai and sequence analysis was done with the help of Dr. Gur Yaari of Bar-Ilan University. The antibodies were characterized in collaboration with Prof. Jonathan Gershoni and Dr. Oren Kobiler of Tel Aviv University. Pseudo-viral neutralization assays were run with the assistance of Dr. Meital Gal-Tanamy and Dr. Moshe Dessau of Bar-Ilan University’s Faculty of Medicine in the Galilee. Neutralization tests for the cocktail of antibodies against the live virus were run in collaboration with Dr. Ben Croker of the University of California, San Diego.

Immunity Memory Cells Stay Stable Over Time After Recovery From COVID-19

Written by AUFTAU on 13 October 2020. Posted in Newsroom.

Researchers of Tel Aviv University examined blood samples from 60 patients at Hasharon Hospital who had recovered from Corona, and found that memory B cells specific to the virus remain stable over time, but concurrently the antibodies in the blood decrease within just a few months. This finding prompted the researchers to raise the possibility that in the event of re-infection with the virus, symptomatic illness will be insignificant. The research was conducted by Dr. Yariv Wine of Tel Aviv University’s Shmunis School of Biomedicine and Cancer Research, and led by post-doctoral fellow Anna Vaisman-Mentesh, together with Dr. Dror Dicker, Director of the Department of Internal Medicine “D” at Hasharon Hospital, and department’s team.

They don’t forget so quickly

Since the SARS-CoV-2 is a new virus, there is as yet no data on immune memory over time among those recovered from the virus. In the current research, Dr. Wine and team checked the level of antibodies, as well as the B cell count in their group of subjects. As has been shown in other previous studies, the antibodies acting on the viral protein responsible for attaching itself to target cells in the host body, develop very quickly – but decay following recovery. In contrast, B cells, that remember the viral proteins and can efficiently reactivate upon reinfection, do not decline in recovered subjects over a period of six months.

“Corona is a serious illness and includes long-lasting side effects,” Dr. Wine explains. “For that reason, rehabilitation centers have been established for those recovering from Corona, such as the one at Hasharon Hospital, and it also enables us to continue examining blood samples even many months after recovery. From among the group of recovered patients who have volunteered to be part of the research, we collected blood samples at predetermined time intervals – 3 months after onset of disease, and again 3 months later. From the data thus gathered, we can say that over at least a 6 month time period, the subjects maintained a stable level of memory B cells specific to the viral protein. The significance of this is that if these subjects become re-infected, their immune system can quickly respond: B cells will create a secondary reaction which may prevent illness. On the other hand, due to the decay of the antibodies, those who have recovered can still be carriers of the virus, and perhaps also be able to infect others.”

Since the antibodies in the blood of those recovered from Corona decay with time, and in some cases even fall below detection threshold just 3 months after recovery, Dr. Wine and his team fear that serological surveys may be providing an inaccurate picture to decision-makers regarding spread of infection.

Concern over problem in reliability results in serological surveys

“Health organizations and the media talk a lot about serological surveys that check the level of antibodies in the blood, as a way of inferring the spread of disease in the population,” Dr. Wine says. “These surveys are very important, but in the light of the data on the decay of antibodies among recovered subjects, we might get a negative result when testing those who were infected in the past. If the antibodies are not maintained over time, and those who have recovered can still carry the virus and infect others, it is challenging to extrapolate from these surveys the breadth of infection spread in the population.”

Dr. Dicker adds that we are in a process of ongoing learning about Corona virus clinical illness when some recovered subjects still carry the virus. These findings add to our understanding of chronic illness from Corona and may shed light on future capabilities of the immune system of these recovered subjects.

Researchers Identified the Genetic Causes of Inherited Hearing Loss in the Jewish Population of Israel

Written by AUFTAU on 30 September 2020. Posted in Newsroom.

In the Jewish population of Israel, until now, seven genes were known to be involved in hearing loss. Now, thanks to a new study led by Zippora Brownstein, PhD, and Prof. Karen Avraham from the Sackler Faculty of Medicine at Tel Aviv University, the number of genes known to be responsible for inherited hearing loss in Israeli Jewish families is 32.

These results have immediate implications for genetic counseling for families with hearing loss and for care of children with hearing loss. The research was in cooperation with scientists from multiple Israeli universities and hospitals, and from the University of Washington in Seattle, the U.S. National Institutes of Health (NIH), Bethlehem University, the University of Iceland, and the University of Maryland. The researchers also identified a mutation in a gene not previously recognized to cause hearing loss in humans. This breakthrough research was published recently in the journal Clinical Genetics.

The 25^th gene

More than 150 genes are known to science to be involved in hearing loss. Genetic diagnoses for inherited hearing loss have previously been difficult, both world wide and in Jewish communities, because any one of so many different genes, and any of many mutations in each gene, could be the cause. Until now, mutations in only seven of the 150 genes had been detected among persons with hearing loss in the Jewish population of Israel. In the current study, which included 88 Israeli families with hearing loss, the researchers identified mutations in 25 additional genes.

Although 24 of the 25 genes are known to cause hearing loss in families worldwide, most of the specific mutations in Israeli Jewish families are newly observed and thus far known only the Jewish community. The 25^th gene, called ATOH1, was found for the first time to cause hearing loss in humans.

^{Organ of Corti of the inner ear labelled with antibodies to show sensory hair cells responsible for hearing. Photo Credit: Shahar Taiber & Prof. Karen Avraham}

“We know that ATOH1 has an important role in the ear,” explains Prof. Avraham, “without it, hair cells of the inner ear – the cells responsible for our hearing – cannot develop properly. Until now, a mutation in this gene was identified only in mice, and the mice had a hearing loss. We found a similar mutation in relatives with hearing loss in a large family in Israel – the first people in the world known to have a mutation in this gene. I believe we will find more families, both in Israel and abroad, with mutations in this gene that cause hearing loss. The goal is that with this information, new treatment possibilities for people with hearing loss will be developed – including gene therapy.”

Prof. Avraham adds: “We surveyed Jewish families throughout Israel with all types of hearing loss: from congenital to older age at onset, and from moderate to profound. Our survey exploited advanced gene sequencing technology, including a custom gene panel that we created, called HEar-Seq. This custom gene panel allowed us to simultaneously sequence all 150 genes known to be involved in hearing loss, and many “candidate genes” as well. HEar-Seq revealed the distribution of genes and their mutations responsible for hearing loss in all the Jewish communities that make up modern Israel. It led us to ATOH1.

Our discoveries have immediate implications for genetic counseling, which can enable families to prevent additional cases of hearing loss through pre-gestational genetic diagnosis and in-vitro fertilization. Also, for many families, treatment and rehabilitation for hearing loss can be tailored to the family’s specific mutation. The findings of this study allow doctors and audiologists in Israel to provide personally tailored treatment to patients with inherited hearing loss.”

The study was funded by the National Institute of Deafness and Communication Disorders of the U.S. National Institutes of Health, the Israel Precision Medicine Program of the Israel Science Foundation, the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, the Hedrich Charitable Trust, and travel grants from the University of Washington Virginia Bloedel Hearing Research Institute.

Prof. Karen Avraham

Zippora Brownstein, PhD

New Program Fosters Well-Rounded STEM Graduates

Written by AUFTAU on 17 September 2020. Posted in Newsroom.

Expansion of the Jack, Joseph and Morton Mandel Center for Humanities in STEM ushers in a new era in the Israeli university curriculum By Rafael Ben-Menashe Beginning in the next academic year, 1,500 incoming students in Engineering, Exact Sciences and Life Sciences will encounter a new opportunity in their studies: they will be able to take three Humanities courses as part of their regular degree requirements. The force behind this move – a first in Israel – is the Jack, Joseph and Morton Mandel Center for Humanities in STEM at TAU. “Students will experience dramatically different learning styles by switching between humanities and STEM subjects,” says Prof. Yochai Oppenheimer, a member of TAU’s Department of Hebrew Literature and Academic Head of the Mandel Center. He describes this change as “a refreshing jump into a pool for the mind” and says that, through the Mandel Center, TAU is embracing a global trend of incorporating liberal arts into science and technology curricula. The focus will be on introductory and survey courses that will instill essential skills of humanistic thought such as critical thinking, debating, writing, ethical analysis and more. Battling a worldwide trend Around the world, enrollment in the humanities has fallen over the last two decades while that of STEM has increased. At Tel Aviv University, the number of undergraduates at the Entin Faculty of Humanities dropped from 2,600 in 2003 to 1,600 in 2018, a reduction of 38% over 15 years. In response, the Jack , Joseph and Morton Mandel Foundation, under the leadership of the late Morton L. Mandel, pioneered the Program for Humanities in Engineering at TAU in 2016. Completely new on the Israeli academic landscape at the time, the Program allowed a group of 25 honors students to add a sizeable humanities module to their engineering studies. They were given generous scholarships along with personal mentors to guide them in course selection. The Program was a great success: Participants praised it and top tech companies expressed eagerness to hire graduates. Based on these positive results, in 2019 TAU established the Jack, Joseph and Morton Mandel Center for STEM and the Humanities to replicate the Jack, Joseph and Morton Mandel Program for Humanities in Engineering for outstanding Exact Sciences and Life Sciences students as well. The newest expansion of the initiative, toward the 2021-22 school year, will extend humanities offerings to all incoming STEM students at TAU. “The Mandel Center reinforces the humanities’ relevance to science and technology, nurturing well-rounded technological leaders in Israel. Presently the Israeli Council for Higher Education is considering duplicating the program at other Israeli universities,” says Oppenheimer. Welcoming uncertainty Students enrolled in Mandel Center-sponsored humanities courses say they provide a bonus, a break from the more regimented styles of thinking in STEM subjects. “In the sciences, we fear questions that don’t ultimately have definitive answers,” says Michal Levin, a fourth-year engineering student. “In the humanities, we are taught to embrace those types of questions.” Similarly, Ido Mellul, a first-year biology student, says: “The program has helped me better formulate philosophical questions in a scientific context. For example, I questioned my lecturers regarding applied ethics in the case of gene-editing technology,” he says. “This was something I didn’t think I could do before.” Levin also points to the Mandel Scholarship she received as a tremendous aid in her studies. “It eliminated the stress of finding work and financing my life while studying.” The courses offered through the Mandel Center cover philosophy, rhetoric, cultural studies, literature and history. “The idea behind the program immediately struck a chord with me,” says Amit Alkoni, a third-year engineering student. “I served in an engineering unit of the Intelligence Corps in the army, and my service helped me envision how effective evaluation of communication and ethics can expand my professional horizons.These are tools I ultimately acquired through studying the humanities.” Last year, shortly before his death, TAU conferred its highest honor, the degree of Doctor Philosophiae Honoris Causa, upon Morton Mandel, an entrepreneur and lifelong Israel supporter, for his visionary support of TAU. “The Mandel Foundation’s generosity has allowed TAU to rejuvenate the humanities, ensuring that TAU students benefit from this crucial school of thought, which in turn benefits Israeli society as a whole,” says TAU President Prof. Ariel Porat. Prof. Jehuda Reinharz, President and CEO of of the Jack, Joseph and Morton Mandel Foundation, adds: “We are delighted to collaborate with Tel Aviv University on this important venture. The combination of STEM subjects with humanities education is precisely the kind of preparation every student should have today and in the future before he/she enters the work force. Given the decline in humanistic education and values this is the time to have such interdisciplinary programs. Tel Aviv University is a pioneer in this far-sighted work across the disciplines, and I am quite certain that it will become a model for many other institutions in Israel and abroad.” Featured image: Mandel Scholars Amit Alkoni and Michal Levin. Photo: Moshe Bedarshi.

Google Awards Competitive Grant to Tel Aviv University for COVID-19 Research

Written by AUFTAU on 15 September 2020. Posted in Newsroom.

Targeting Melanoma

Written by AUFTAU on 10 September 2020. Posted in Newsroom.

Researchers at Tel Aviv University, led by Prof. Ronit Satchi-Fainaro from the Department of Physiology and Pharmacology at the Sackler Faculty of Medicine, developed an innovative nanotechnological drug delivery system that significantly enhances the effectiveness of treatment for the aggressive skin cancer melanoma. The nanocarrier is a biocompatible and biodegradable polymer, which comprises repeating units of glutamic acids (PGA- polyglutamic acid), packaging together two biological drugs belonging to different families with proven efficacy for the treatment of melanoma: BRAF inhibitors (Dabrafenib) and MEK inhibitors (Selumetinib, approved for use in children with NF1 – neurofibromatosis type I).

Prof. Satchi-Fainaro: “One of the major obstacles of the biological treatments is that after a while, the cancer cells develop resistance to the drugs. We assume that by precise delivery of two or more targeted drugs that will attack the cancer cells forcefully and simultaneously from different directions, we can delay or even prevent the acquisition of this drug-resistance.”

The research group included PhD students Evgeni Pisarevsky, Dr. Rachel Blau and Yana Epshtein from Prof. Satchi-Fainaro’s research laboratory at TAU’s Sackler School of Medicine. The paper was published as the cover article of the August 2020 issue of Advanced Therapeutics.

Prof. Satchi-Fainaro: “In this project, we looked for a solution to a problem often associated with drug cocktails: Today, most oncological treatments are administered in the form of cocktails of several medications; However, despite the fact that all drugs are administered to the patient simultaneously, they do not reach the tumor at the same time, due to differences in basic parameters – like how long they survive in the bloodstream (i.e. half-life), and the time it takes each drug to reach the tumor tissue. Thus, in most cases, the medications do not work concurrently, which prevents them from attaining optimal synergistic activity.”

Responding to these challenges, the researchers developed an innovative, efficient and biodegradable drug delivery system. Two biological drugs, known to be effective for the treatment of melanoma, Dabrafenib and Selumetinib, (inhibiting two different components – BRAF and MEK respectively – in the biological pathway which is over-activated in melanoma), were chosen, with the intention of delivering them jointly to the tumor by using a nanocarrier. The drug nanocarrier chosen for the task was PGA, a polymer of glutamic acid – one of nature’s most common amino acids. Developed in Prof. Satchi-Fainaro’s lab several years ago, the nanocarrier has already been tested successfully for treating pancreatic, breast and ovarian cancer in animal models.

In search of an optimal ratio

First, the researchers determined the optimal ratio between the two medications – based on levels and types of toxicity, as well as the resistance mechanism developed by cancer cells for each medication – to ultimately ensure maximum effectiveness, minimal toxicity and optimal synergistic activity. Another important advantage of joint delivery is reduced dosage: a much lower dose is required compared to each drug when administered independently.

The next step was using chemical modifications to enable bonding between the polymeric carrier and the chosen drugs. This combined system can travel through the body with total safety, inflicting no damage to healthy tissues. Upon reaching the cancer cells, the nanocarrier encounters proteins of the cathepsins enzyme family, which are highly activated in malignant tumors. The proteins degrade the polymer, releasing the drugs which become active and join forces to attack the tumor. Prof. Satchi-Fainaro: “It’s like several passengers riding in one cab and getting off together at the same address. They all arrive at the same destination, right at the same time.”

Promising results

Tested on a mouse model of melanoma, the new treatment showed promising results: The nanocarrier delivered the two drugs to the tumor and released them there simultaneously in quantities about 20 times greater than those that reach the tumor when similar doses of the same medications are administered independently. In addition, the therapeutic effect achieved by the drugs delivered by the nanocarrier lasted much longer – 2-2.5 times compared to control group and the group treated with free medications. According to the researchers, this means that the new platform enables much lower dosages – about one third of the dose required in regular drug cocktails, and the treatment as a whole is both safer and more effective. Also, if needed, the new approach allows for dosages that are much higher than the maximum dosage permissible in current methods, thereby enhancing the effectiveness of the treatment even further.

Prof. Satchi-Fainaro: “In this project, we developed an innovative drug delivery system for treating melanoma, delivering two proven medications and releasing them simultaneously at the tumor site. The treatment proved both safer and more effective than the same medications administered as a cocktail. Moreover, our new platform is highly modular and can be used for delivering a vast range of medications. We believe that its potential for enhancing therapeutics for different diseases is practically endless.”

The study was funded by the Israel Cancer Research Fund (ICRF), the European Research Council (ERC), Israel’s Ministry of Health (EuroNanoMed-II program), the Melanoma Research Alliance, the Morris Kahn 3D BioPrinting for Cancer Research Initiative and the Israel Science Foundation (ISF).