TAU researchers develop new treatment for rare genetic disorder
Adolescents and young adults with familial adenomatous polyposis bear a high risk of developing cancer
Why does FAP lead to colon cancer?
“To prevent the development of colorectal cancer, FAP patients are closely monitored via frequent colonoscopies to locate and remove their polyps,” Prof. Rosin-Arbesfeld says. “However, some patients must have their colons removed at a very young age, which dramatically affects their quality of life.” In its normal state, APC promotes the production of a protein that inhibits cancer development. But mutations to the APC gene produce an inactive protein that is unable to prevent the development of the polyps. In some FAP patients, the mutations in the APC gene are what are called “nonsense mutations.” “Each sequence of three nucleotides in the DNA is a code that tells the cell to produce a certain amino acid, which are the building blocks of the proteins produced in the body’s cells,” Prof. Rosin-Arbesfeld explains. “At the end of the protein coding sequence, there is usually a ‘stop codon’ to stop the protein production. But in FAP patients with a nonsense mutation, the APC’s stop codon appears prematurely, so the protein production stops prematurely, creating an inactive protein.”Preventing surgical intervention
Previous experiments on cell cultures and mouse models in Prof. Rosin-Arbesfeld’s laboratory revealed that certain types of antibiotics caused cells to “ignore” the mutation stop codon and a normal protein resulted. These trials yielded promising results that led to the clinical trial at Tel Aviv Sourasky Medical Center. “Since the relevant antibiotics were already approved for human use, we decided to move directly from the laboratory to the clinic and to examine the treatment of FAP patients,” says Prof. Rosin-Arbesfeld. In the clinical study carried out by Prof. Kariv and Dr. Shlomi Cohen, director of the Pediatric Gastroenterology Unit at Dana-Dwek Children’s Hospital, 10 FAP patients received the novel antibiotic therapy. Eight of them completed the treatment, which lasted four months. Colonoscopies performed during and after the treatment showed that in seven patients the polyps significantly decreased in number. Moreover, the positive effects of the treatment were evident a year after it began. “Our goal as therapists, in addition to preventing cancer, is to improve the quality of life of our patients and their families and to enable them to live as full and normal lives as possible,” Prof. Kariv concludes. “The new therapeutic approach we are developing may allow patients to delay surgical intervention or even prevent it entirely.” The researchers recently won Tel Aviv University’s SPARK grant, which supports the development of applied research.A better way to kill tumor cells
Engineered cells may be harnessed in new immunotherapy for cancer patients, Tel Aviv University researchers say
Using the body’s own immune system
“Chemotherapy damages all fast-growing cells, including hair follicles and cells that line the gastrointestinal tract, and this attack on healthy cells causes serious side effects, which include hair loss, nausea, mood changes, pain, anaemia, nerve and muscle problems, and kidney issues,” explains Dr. Carmi. “Immunotherapy, on the other hand, is a type of biological therapy that uses the body’s own immune system to seek out and destroy cancer cells. Engineered T cells have been proven very successful in treating blood cancer but attempts to use them to fight solid cancers have been disappointing. “Our engineered cells have now shown efficacy in attacking solid tumors as well,” Dr. Carmi says. CAR T-cell therapy is a form of immunotherapy that uses altered T cells to fight cancer. T cells are a type of lymphocyte, or white blood cell, that plays a central role in the immune response. T cells are collected from the patient and modified in the lab to produce structures called CARs on their surface. These receptors allow the T cells to attach to a specific antigen on the tumor cells and kill them.Fewer side effects, more precision
Side effects from immunotherapy may include severe inflammation, caused by an overactive immune system working to fight tumor cells. “Patients who utilize CAR T-cell therapy experience significantly fewer side effects than with chemotherapy,” adds Dr. Carmi. “And while chemotherapy is only effective while the drug is in the body, immunotherapy provides long-lasting protection against cancer. “Our lab discovered a distinct subset of helper T cells, also known as CD4+ T cells, that express the high-affinity receptor for IgG – an antibody – and efficiently kill tumor cells coated with these antibodies,” explains Dr. Carmi. “This method uses CAR T-cell therapy and combines it with antibody specificity. Based on this discovery we were able to engineer novel T cells with enhanced tumor-killing activity and higher specificity, compared with other T cell-based therapies for cancer. “Our engineered cells have the potential to overcome barriers usually faced by CAR T-cell therapy and have shown efficacy in solid tumors. This finding has the capability to change the way cancer is treated, demonstrating that the immune system can be utilized to identify and fight all types of cancer.”TAU launches new center for quantum science & tech
The center will bring together twenty labs from across campus and offer academic programs as well as promote international ties
Twenty labs from different disciplines
TAU launches new center for quantum science & tech
The center will bring together twenty labs from across campus and offer academic programs as well as promote international ties
Twenty labs from different disciplines
TAU Alumni lead The Marker’s 40 Under 40 list
The Marker magazine has published its list of 40 most influential people under 40 in Israel for 2019, and the TAU Alumni community has 12 entries – more than any other university!
Our 12 influencers are:
- Ayelet Perlstein, Counselor for Israel in the IDB Invest at Inter-American Development Bank, alumna of the Coller School of Management
- Areen Safady Atila, Attorney at the Israeli State Attorney’s High Court department, alumna of the Faculty of Law
- Dr. Nadav Levy, Director of the public transportation department at the Tel Aviv-Jaffa Municipality, alumnus of the Porter School of Environmental Studies
- Sapir Caduri, Software Engineer at Google Israel, alumna of the Blavatnik School of Computer Science
- Roni Bonjack, Head of Developer Programs – Europe, Middle East and Africa at Facebook, alumna of the faculty of Engineering
- Dr. Shiri Chechik, Alumna and Researcher at the Blavatnik School of Computer Science
- Leor Roseman, Researcher at the Imperial College London’s Centre for Psychedelic Research, Alumnus of the Faculty of Life Sciences and the School of Psychology
- Yael Kochman, Partner & CEO at Re:Tech Innovation Hub, Alumna of the Faculty of Scocial Sciences & Coller School of Management
- Miki Strasburger, VP Commerce & Aviation at EL AL Israel Airlines, Alumnus of the Coller School of Management
- Sagi Ben Simon, Founding Partner at Beta Finance, Alumnus of the Faculty of Scocial Sciences & Coller School of Management
- Imri Galai, General Manager at Wolt Israel, Alumnus of the Coller School of Management
- Hisham Abdulhalim, Product Manager at PayPal, Masters Degree Student at the Faculty of Humanities
Each is a source of pride and honor for TAU!
The full project (in Hebrew)>
TAU among top 10 universities for venture capital-backed entrepreneurs
Joining Stanford, UC Berkeley, and MIT, TAU is the only non-U.S. university to make top 10 of global VC list
Tel Aviv University has been ranked eighth in the master list of 50 global universities producing the most venture capital-backed entrepreneurs, according to the 2019 PitchBook Universities Report. The top seven universities were all American, led by Stanford University and the University of California, Berkeley.
TAU appears on the list for the sixth year in a row, powerfully reflecting the university’s continuing success in the global business/investor community. TAU came in ahead of Yale University (ranked at #11), University of California, Los Angeles (#12), and Princeton University (#13). Three other Israeli universities made the PitchBook cut: The Technion-Israel Institute of Technology (#14), The Hebrew University of Jerusalem (#34), and Ben-Gurion University of the Negev (#49).
According to PitchBook, 694 TAU graduates-turned-entrepreneurs founded 577 companies raising $10.6 billion in a first round of venture funding in the period between January 2006 and August 2019. TAU was also ranked 13th in the list of the 25 top MBA programs, which was led by Harvard University.
At the center of innovation
TAU is Israel’s largest and most diverse university, consistently rated among the top 100 research universities globally. Located in the heart of Tel Aviv, the second largest technology sector in the world, TAU is the innovation hub of the “Start Up Nation.” With over half the 30,000+ student body engaged in multi-disciplinary research, TAU is uniquely positioned as an incubator of groundbreaking ideas.
As a venture capital data provider, PitchBook is recognized for its exhaustive data platform, which includes information on tens of thousands of VC-backed companies, investors, and service providers. PitchBook‘s database taps into the educational backgrounds of over thousands of VC founders worldwide.
The list ranks the top 50 universities that produced VC-backed founders on a global basis and is based on the number of founders that received first-round venture funding between January 1, 2006, and August 15, 2019.
Coral danger: breakdown in spawning could mean extinction
Synchronized coral spawning has become erratic, endangering the long-term survival of coral species, Tel Aviv University researchers say
Coral reefs are among the most diverse and productive ecosystems on our planet. But due to climate change and other human stressors, reef-building corals that reproduce by means of broadcast-spawning — the simultaneous release of eggs and sperm into open water — may now be under threat of extinction.
A new Tel Aviv University study finds that the highly synchronized, iconic spawning events of certain reef-building corals in the Gulf of Eilat/Aqaba, Red Sea, have completely changed over time and lost their vital synchrony, dramatically reducing chances of successful fertilization.
According to the research, led by Prof. Yossi Loya and PhD candidate Tom Shlesinger of TAU’s School of Zoology and published in Science, the breakdown in coral spawning synchrony has led to a dearth of new recruits and stagnant aging populations, creating circumstances for extinction.
It’s all in the timing
“Coral spawning, often described as ‘the greatest orgy in the world,’ is one of the greatest examples of synchronized phenomena in nature,” explains Prof. Loya. “Once a year, thousands of corals along hundreds of kilometers of a coral reef release their eggs and sperm simultaneously into the open water, where fertilization will later take place. Since both the eggs and the sperm of corals can persist only a few hours in the water, the timing of this event is critical.”
Successful fertilization, which can take place only within this narrow time window, has led to the evolution of a precise spawning synchrony. Such synchronicity relies on environmental cues: sea temperature, solar irradiance, wind, the phase of the moon and the time of sunset.
In 2015, the researchers initiated a long-term monitoring of coral spawning in the Gulf of Eilat/Aqaba. Over four years, they performed 225 night field surveys lasting three to six hours each during the annual coral reproductive season from June to September and recorded the number of spawning individuals of each coral species.
“We found that, in some of the most abundant coral species, the spawning synchrony had become erratic, contrasting both the widely accepted paradigm of highly synchronous coral spawning and studies performed on the exact same reefs decades ago,” says Shlesinger.
Extinction through reproductive failure
The researchers then investigated whether this breakdown in spawning synchrony translated into reproductive failure. They mapped thousands of corals within permanent reef plots, then revisited these plots every year to examine and track changes in the coral community — i.e., how many corals of a given species had died compared with new juveniles recruited to the reef.
“Although it appeared that the overall state of the coral reefs at Eilat was quite good and every year we found many new corals recruiting to the reefs, for those species that are suffering from the breakdown in spawning synchrony, there was a clear lack of recruitment of new juvenile generations, meaning that some species that currently appear to be abundant may actually be nearing extinction through reproductive failure,” says Shlesinger.
The future of corals?
“Several possible mechanisms may be driving the breakdown in spawning synchrony that we found,” Prof. Loya concludes. “For example, temperature has a strong influence on coral reproductive cycles. In our study region, temperatures are rising fast, at a rate of 0.31 degrees Celsius per decade, and we suggest that the breakdown in spawning synchrony reported here may reflect a potential sublethal effect of ocean warming. Another plausible mechanism may be related to endocrine (hormonal) disrupting pollutants, which are accumulating in marine environments as a result of ongoing human activities that involve pollution.”
“Regardless of the exact cause leading to these declines in spawning synchrony, our findings serve as a timely wake-up call to start considering these subtler challenges to coral survival, which are very likely also impacting additional species in other regions,” says Shlesinger. “On a positive note, identifying early-warning signs of such reproductive mismatches will contribute to directing our future research and conservation efforts toward the very species that are at potential risk of decline, long before they even display any visible signs of stress or mortality.”
Protein Mapping Pinpoints Why Most Metastatic Melanoma Patients Do Not Respond to Immunotherapy
Lipid metabolism found to affect cancer cells’ visibility to the immune system, say TAU, Sheba Medical Center researchers
Tel Aviv University and Sheba Medical Center researchers say they have discovered why more than half of patients with metastatic melanoma do not respond to immunotherapy cancer treatments.
Wielding proteomics, an innovative “protein mapping” approach, a team of researchers led by Prof. Tami Geiger, Prof. Gal Markel, and Dr. Michal Harel of TAU’s Sackler School of Medicine and Sheba’s Ella Lemelbaum Institute for Immuno-Oncology have answered the burning question: Why do immunotherapy treatments greatly help some patients with melanoma but not affect 60 percent of metastatic melanoma patients?
The researchers, whose findings were published on September 5 in Cell, compared the responses of 116 melanoma patients to immunotherapy — one group in which immunotherapy was successful and a second in which immunotherapy was not successful. Harnessing proteomics, a powerful protein mapping technology, they discovered differences in the metabolism, or energy production process, of the cancer cells of the two groups.
“In recent years, a variety of cancer immunotherapy therapies have been used, therapies that strengthen the anti-cancer activity of the immune system,” explains Prof. Markel, a senior oncologist and scientific director of the Ella Lemelbaum Institute. “These treatments have been shown to be highly effective for some patients and have revolutionized oncology. However, many patients do not respond to immunotherapy, and it is critical to understand why.
“Can we predict who will respond? Can we alter treatment in order to increase responses? In our research, we focused on metastatic melanoma, a devastating disease that until recently had no efficient treatments. It was clear to us that pre-treatment samples from responders and non-responders would be key.”
To better understand treatment resistance mechanisms, the scientists examined tumors taken from 116 patients using proteomics.
“In the proteomic lab, we use an instrument called a mass-spectrometer, which enables global mapping of thousands of proteins,” explains Prof. Geiger, head of TAU’s Proteomics Lab. “We then followed up with extensive computational analysis to identify the proteins that differentiated between the response groups.”
The proteomic comparison identified major differences between responders and non-responders to immunotherapy. “In the responders, we found higher levels of proteins associated with lipid metabolism, which led to better recognition by the immune system,” says Prof. Geiger.
In collaboration with the Salk Institute in San Diego and Yale School of Medicine, researchers then examined their findings in melanoma tissue cultures and a mouse model of metastatic melanoma.
Using genetic engineering, they were able to silence the mechanism responsible for fatty acid metabolism.
“We found that upon silencing this metabolic pathway, the cancer cells manage to ‘hide’ from T-cells that are supposed to detect and destroy them,” says Prof. Geiger. “As a result, cancer in these mice developed at a faster rate compared to the control group.
“In our study, we identified a significant difference between melanoma patients who live for years thanks to immunotherapy, and patients who are not at all affected by the treatment.”
“These findings can also be relevant to many other malignancies,” adds Prof. Markel. “Now, in subsequent studies, we are looking for ways to improve the response to immunotherapy and expand the circle of patients who benefit from it. In addition, we are looking for a method that will allow clinicians to anticipate which patients will respond to treatments.”
Can we beat the heat?
The creative ways animals, plants and computers have of using every drop of water when the temperatures rise
It’s no secret that global warming is upon us. We’ve experiencing more and more extreme conditions, with longer dry periods, shorter but stormier rainy seasons, and increased flooding. At Tel Aviv University, our researchers are monitoring the animals and plants that live and thrive in extreme conditions, learning about the unique mechanisms they’ve developed, and developing ways that will help us, and even our electronics, survive the intense heat.
Study the beetle’s ways
Dr. Bat-El Pinchasik, from Tel Aviv University’s School of Mechanical Engineering, was fascinated by the creative ways beetles and lizards have of utilizing the water around them, and today she develops biomimetic systems that mimic desert animals’ solutions to the water problem. “Insects and lizards that live in areas without a lot of access to water have to collect it from other sources, for example, from the air and from morning fogs,” explains Dr. Pinchasik. “At times, when temperatures are lower, when there is higher wind and humidity in the air – the air condenses on their bodies. Evolution has made them a ‘smart surfaces’ that spontaneously transports the water that’s been collected directly into their mouths.”
The Texas horned lizard, for example, has three-dimensional trenches on its back that serve as its personal superhighway. The Namib Desert beetle’s body is mostly hydrophobic (water repellent), but is also sprinkled with hydrophilic micrometric protrusions, which concentrate droplets of water in specific places, and roll them directly into the beetle’s mouth. “Our aim is to define the rules that make these sorts of mechanisms efficient, develop smart materials similar to the ones the beetles have, and to use advanced 3D printing technologies to build systems that can change lives in areas where water is inaccessible,” says Dr. Pinchasik.
It turns out that there are many places in the world where access to water is a problem, and strange as it may sound, it’s not just countries located in deserts. “Even in Europe, which is very rich in water, there are places where there are no systems that move water from place to place,” she explains, continuing: “One of the problems is that most systems today aren’t based on smart materials, and the quantities they manage to collect at a time are small. That’s what we want to improve. Building local water collection points and low-cost efficiency will pay off in a big way.”
Save every drop. Texas horned lizards.
Switching to the night shift
Think animals are creative? You won’t believe how plants learned to endure and survive extreme climate. Dr. Nir Sade, from the School of Plant Science and Food Security at the George S. Wise Faculty of Life Sciences, studies how wild plants cope with the increase in dryness and heat. He seeks out and isolates the traits and mechanisms of resilience they develop and helps to introduce them, through genetic engineering and hybridization, to the crops accustomed to a moist and luxurious life, that are now unable to keep up with the changes in conditions.
“Plants have a number of ways to deal with global warming and the extreme conditions it brings with it,” Dr. Sade explains. “The first is evolutionary, in which different plants have changed their photosynthesis process (a process in which the plant absorbs carbon dioxide and light, turning them into energy and emitting oxygen in return). Some have learned to streamline the process even under conditions of high heat and dryness. Corn, for example, has learned to concentrate the carbon dioxide it absorbs into specific, unique cells in its leaves, instead of the entire leaf, thus essentially “enriching” the carbon dioxide to maintain the efficiency of the process. Others developed a more extreme mechanism and shifted into night mode. Cacti, for example, absorb carbon dioxide at night instead of during the day, when the temperature and water loss are not as high, and save the fixation process for daytime. That’s how they manage to survive. “
Changing to night mode. Cacti in the desert.
And there are other strategies as well: “Some plants don’t want to deal with the conditions threatening them and prefer to escape them. These have adopted the motto: live fast, die fast. That is, they’re accelerating their life cycle,” says Dr. Sadeh. “It’s a strategy particularly suited for extreme conditions like a Mediterranean climate, but it comes at a cost: the amount the plant produces can be smaller.”
Some plants prefer to “look away” until the storm passes, which means avoiding extreme conditions, with the help of water retention in the leaf. “Plants that use the avoidance mechanism reduce water loss from the leaves by closing the stomata (unique cells responsible for the carbon dioxide water expulsion), and/or reducing the surface area of foliage (thus reducing the area from which water is lost). They also invest in water transfer efficiency, from the roots up to the leaves, by deepening and expanding the roots.”
The toughest ones have developed a tolerance for the extreme conditions. “This is a group of plants that, despite the earth getting dryer, have learned to biochemically adapt, create molecules and synthesize proteins that protect them from harm,” says Dr. Sade, adding: “Because most forecasts do not anticipate an improvement in the extreme climate change the world is experiencing, many resources are now being invested by commercial companies, through to government investments and university labs, to understand the molecular and genetic basis of plant response to extreme conditions.”
Be tough. Right: genetically engineered tomato shrubs that are irrigated with salt water, next to regular tomato shrubs
What do a laptop and a horse have in common?
Not only the flora and fauna need water to cool down and freshen up. Ever left your cellphone in the sun, to later find it not working? Without sufficient cooling, this is what happens to all electronic components. Nowadays, cooling systems are installed in computers that run a cooling liquid straight on the computer chip, through pipes only a few millimeters in diameter. The Micro Flow and Heat Transfer Laboratory of Dr. Herman Haustein, at the Iby and Aladar Fleischman Faculty of Engineering, investigates cooling mechanisms that are as thin as a single strand of hair. It’s a breakthrough study for building systems in the present and in the future.
“In these tiny sizes, phenomena that are usually ignored in systems like our home plumbing, are central and must be taken into account in order to characterize the flow, “explains Ido Laufer, an engineer at Dr. Haustein’s lab. “The need for our research is at the forefront of the high-tech industry. For example, today, one of the factors limiting the electronics industry is the density of components that require power supply. On the one hand we want to fit as many components as possible in as little space as possible, and on the other – to find ways to cool them efficiently,” he continues. “In order to cool components, we need a cold flow supply, which will remove heat from micron-sized systems (a hair is 100-50 microns in diameter). Our research contributes to the design of complex electronic systems such as computers, defense systems, and medical devices.”
The capabilities of the equipment in Dr. Hausstein’s lab are unique, therefore it’s used by researchers from many different disciplines, from the study of bats to the discovery of new materials. One popular field is biology. “It’s because every organism is dependent on the flow of liquids for its food supply and for removing waste, through similarly sized tubes,” Laufer reveals. “In the hot days we’re currently experiencing, all the balancing of temperatures and maintaining body heat depends on the flow of liquids in our bodies. Water that we drink should reach the cells through the blood vessels, bodily fluids should reach the sweat glands and from there reach the skin to cool us, and more. The equations we’re developing aren’t dependent on a specific field of study, but provide a mathematical, physical solution, so they can be used in biological research as well as in other disciplines.”
Researcher Rona Eckert of the School of Zoology, uses the unique equipment in the laboratory, as part of a study on heat conservation in the body of moths