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IMRIC Scientist Awarded for Work in Stem Cells & Regenerative Medicine

18/07/2016

Dr. Yosef Buganim is a young researcher at the Institute for Medical Research Israel-Canada (IMRIC), part of the Hebrew University’s Faculty of Medicine

Dr. Yosef Buganim, a research scientist at the Hebrew University of Jerusalem, has been honored by the American Association for the Advancement of Science (AAAS), the prestigious journals Science and Science Translational Medicine, and the Boyalife industrial research consortium, for his work in stem cells and regenerative medicine. (See Buganim’s essay in Science at http://science.sciencemag.org/content/352/6292/1401.full).

Dr. Buganim is a young researcher who recently joined the Department of Molecular Biology and Cancer Research at the Institute for Medical Research Israel-Canada (IMRIC, http://imric.org). Part of the Hebrew University’s Faculty of Medicine, IMRIC is one of the most innovative and multidisciplinary biomedical research organizations in the world.

Awarded for the first time this year, the Boyalife Science & Science Translational Medicine Award in Stem Cells & Regenerative Medicine honors researchers for outstanding contributions in stem cell research and regenerative medicine around the globe. AAAS, Science, and Science Translational Medicine joined efforts with Boyalife, an industrial-research consortium formed in Wuxi, China, in 2009, to sponsor the award.  Composed of prominent researchers, the judging panel was co-chaired by a Science and a Science Translational Medicine editor.

At his Hebrew University laboratory, Buganim uses somatic cell conversion models to identify and investigate the elements that facilitate safe and complete nuclear reprogramming. As a postdoctoral fellow at the Whitehead Institute for Biomedical Research at MIT, he used single-cell technologies and bioinformatic approaches to shed light on the molecular mechanisms that underlie the reprogramming of somatic cells to iPSCs.

Regenerative medicine is a developing field aimed at regenerating, replacing or engineering human cells, tissues or organs, to establish or restore normal function. Embryonic stem cells have enormous potential in this area because they can differentiate into all cell types in the human body. However, two significant obstacles prevent their immediate use in medicine: ethical issues related to terminating human embryos, and rejection of foreign cells by a patient's immune system.

In 2006, Japanese researchers discovered that it is possible to reprogram adult cells and return them to their embryonic stage, creating functional embryonic stem-like cells. These cells are known as induced pluripotent stem cells (iPSCs), and constitute a solution to these two obstacles. In addition, these cells provide a good basis for modeling diseases and finding medical solutions, because they can be reproduced from different patients and different diseases.

Despite these cells’ enormous potential, their quality is still not sufficient to be used in clinical practice, and there is a need to find the best protocol that will enable production of high-quality iPSCs that will not endanger patients.

Dr. Buganim’s laboratory has made two major breakthroughs in this area, representing a major step forward in the field of regenerative medicine and transplantation.

Project A: To improve the quality of embryonic stem cells, Dr. Buganim and colleagues conducted bioinformatics analyses which pointed to four new key genes capable of creating iPSCs from skin cells, of superior quality to stem cells in current use. These cells produced in his laboratory (in this case mouse cells) are able to clone a whole mouse at a much higher percentage (80%) than other iPSCs (30%). This test is the most important one determine the quality of the cells.

Project B: Many women suffer recurrent miscarriages and abnormal development of the placenta, which causes fetal growth restriction and in some cases produces children with mental retardation. Dr. Buganim’s lab found the key genes of the placenta stem cells and by expressing them in surplus in skin cells, created placental iPSCs. These cells looked and behaved like natural placental stem cells. Various tests showed that these cells have cell-generating capability in a Petri dish and inside a placenta that develops following a transplant. These cells have potential for use in regenerative medicine in cases of problematic placental functioning. The success of this project may enable women with placenta problems to give birth to healthy children and rescue pregnancies at risk of dysfunctional placenta. (See details at http://new.huji.ac.il/en/article/27928.)

Forward-looking: Alongside creating specific cell types (e.g. nerve cells in patients with Parkinson's disease, ALS and Alzheimer) from a patient’s skin cells, a potential future use of iPSCs is the creation of whole organs (such as heart, liver or kidney) in a suitable animal model using cells taken from the patient.

Citation: Science, Vol. 352, Issue 6292, pp. 1401, DOI: 10.1126/science.aag1215 (link: http://science.sciencemag.org/content/352/6292/1401.full)

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Boyalife Group, previously known as the International Consortium of Stem Cell Research (INCOSC), was founded in July 2009 in Wuxi, China. In July 2015, Boyalife became the world’s first Stem Cell Bank accredited by AABB standard of Somatic Cell. Through subsidiaries, the company is also engaged in regenerative medicine, genomics, animal cloning, innovative drug discovery and disease modeling.

The American Association for the Advancement of Science (AAAS) is the world's largest general scientific society, and publisher of the journals Science, Science Translational Medicine, Science Signaling and Science Advances. The non-profit AAAS -- www.aaas.org -- is open to all and fulfills its mission to "advance science and serve society" through initiatives in science policy, international programs, science education, and more.

The Institute for Medical Research-Israel Canada (IMRIC), in the Hebrew University of Jerusalem's Faculty of Medicine, is one of the most innovative biomedical research organizations in Israel and worldwide. IMRIC brings together brilliant scientific minds to find solutions to the world's most serious medical problems, through a multidisciplinary approach to biomedical research. More information at http://imric.org.

The Hebrew University of Jerusalem is Israel’s leading academic and research institution, producing one-third of all civilian research in Israel. For more information, visit http://new.huji.ac.il/en.

IMRIC Scientist Awarded for Work in Stem Cells & Regenerative Medicine
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Single Dose of Novel Peptide Protects Cognitive Function After Mild Traumatic Brain Injury (mTBI)

11/07/2016

New molecules, developed by Hebrew University of Jerusalem scientists, reduce inflammation, cell death and cognitive impairments following traumatic brain injury in mice

Whether at school, in car accidents, on the sports field or the battlefield, mild traumatic brain injury (mTBI) is a common part of our lives. It is especially frequent among children, athletes, and the elderly. Now, scientists at the Hebrew University of Jerusalem have shown that a single dose of a new molecule they developed can effectively protect the brain from inflammation, cell death, and cognitive impairments that often follow a mild traumatic brain injury.

Because it lacks visible external signs or objective structural brain damage, mTBI is an under-diagnosed injury. Yet it is often accompanied by long-lasting cognitive, behavioral and emotional difficulties associated with biochemical and cellular changes.  While most symptoms of mTBI are substantially resolved within days or weeks of the injury, up to 50% of mTBI patients experience symptoms at one-year post-injury. These can include psychological symptoms, subjective cognitive impairments, and somatic (physical) complaints.

These changes could result from an increase in glutamate levels, oxidative stress, opening of the blood-brain-barrier, and in particular inflammatory activity followed by cell death (apoptosis).  

Currently there is no effective treatment for patients with mTBI. 

“It is widely known that external or internal injury strongly activates the inflammatory response and leads to cell death (apoptosis) through the MAPK pathways, which are involved in the cellular responses that lead to inflammation in brain cells,” explains Prof. Daphne Atlas, from the Department of Biological Chemistry in the Alexander Silberman Institute of Life Sciences at the Hebrew University of Jerusalem. “Therefore, for reversing the effects of mTBI it is essential to calm the inflammatory pathways.”

At her laboratory in Jerusalem, Prof. Atlas has developed new molecules derived from the active site of Trx1, called thioredoxin-mimetic peptides (TXM-peptides). Thioredoxin (Trx1) is a major protein that maintains the oxidation/reduction state of the cells. In its reduced form it is bound to another protein (ASK1), which is released upon oxidation of Trx1 and activates a chain of enzymatic reactions that lead to inflammation. 

The newly-synthesized thioredoxin-mimetic peptides (TXM-peptides) have been shown to protect cells from early death via the activation of inflammatory pathways. Comprising 3 or 4 amino acids, these peptides have dual activity: they mimic the antioxidant activity of Trx1, and simultaneously inhibit the activity of enzymes called MAPK within the inflammatory pathway, preventing inflammation and cell death.

TXM-CB3 was previously shown to effectively lower MAPK activity in animal models of asthma and in the brain of rat model of diabetes [Kim et al 2011; Bachnoff et al 2011; Cohen-Kutner et al 2013, 2014]. The peptides managed to cross the blood-brain barrier and improve the condition of brain cells by lowering the inflammatory processes.

In the current study, published in the peer-reviewed journal PLOS ONE, Prof. Atlas and colleagues explored the impact of TXM-peptides, TXM-CB3 and TXM-CB13 (DY70; provided by OneDay Biotech and Pharma Ltd), on preventing mTBI cognitive secondary injury.  The experiments were performed in collaboration with researchers at Tel Aviv University, Prof. Chagi Pick and Dr. Renana Baratz-Goldstein

Researchers induced cognitive impairments in anesthetized mice by a weight drop resulting in mild traumatic brain injury. The mice showed a decrease in spatial memory in the Y-maze test and a loss in visual learning ability in the novel object recognition test.  Lower learning ability was also detected 30 days post injury in the mTBI mice.

In these two independent tests, a single dose of either one of the TXM-peptides administered 60 minutes post-injury, at a 50 mg per kg of body weight, significantly improved the decline in cognitive performance and learning ability at 7 and 30 days post injury. In addition, the two TXM-peptides were found highly effective at inhibiting the MAPK activity in neuronal cells grown in tissue culture.

“This research demonstrates the potential for TXM-peptides to significantly reduce cognitive impairment after mild traumatic brain injury,” said Prof. Atlas. “Further studies are required to establish and examine the potential of a single dose of TXM-peptide in preventing damage if administered even one hour after brain trauma in human scenarios — for example, in chronic traumatic encephalopathy observed in American football players, which result from multiple concussions and other types of blows to the head.

"Another advantage to using peptides is in significantly reducing the risk of causing toxic effects, because they consist of amino acids which are the natural building blocks comprising cell proteins, in contrast to the use of drugs that are not natural.  So TXM-CB3 and TXM-CB13 are promising treatment candidates to prevent secondary damage that affect brain function,” said Prof. Atlas.

About The Hebrew University of Jerusalem

The Hebrew University of Jerusalem is Israel’s leading university and premier research institution. Founded in 1918 by such innovative thinkers as Albert Einstein, Martin Buber and Sigmund Freud, the Hebrew University is a pluralistic institution where science and knowledge are advanced for the benefit of humankind. The Hebrew University is ranked internationally among the top 100 universities in the world, and first among Israeli universities. Serving 23,500 students from 85 countries, the Hebrew University produces a third of Israel’s civilian research, and its faculty are at the forefront of the international academic and scientific communities. For more information, please visit http://new.huji.ac.il/en.

FUNDING: This research was supported by the Ari and Regine Aprijaskis Fund at Tel-Aviv University, and by The H.L Lauterbach Fund (Hebrew University) to Daphne Atlas.

CITATION: Baratz-Goldstein, R., Deselms, H., Heim, L. R., Khomski, L., Hoffer, B. J., Atlas, D., & Pick, C. G. (2016). Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI). PLoS ONE11(6), e0157064. http://doi.org/10.1371/journal.pone.0157064 (Link:  http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157064)

Single Dose of Novel Peptide Protects Cognitive Function After Mild Traumatic Brain Injury (mTBI)
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Hebrew University Ranked #17 in Asia, First in Israel, in 2016 Times Higher Education Asia University Rankings

21/06/2016

Editor of Times Higher Education Rankings: "Hebrew University research is pushing the boundaries of knowledge and is being cited globally."

In the 2016 Times Higher Education Asia University Rankings released today, the Hebrew University of Jerusalem is ranked #17 in Asia. The Hebrew University moved up 8 spots from #25 last year, to #17 this year. The Hebrew University is also the highest-rated Israeli university in the new Asia University Rankings.   

These are the fourth annual Asia University Rankings, Times Higher Education’s ranking of the top 200 universities in Asia. The full rankings table can be found at https://www.timeshighereducation.com/world-university-rankings/2016/regional-ranking.

Phil Baty, Editor of Times Higher Education Rankings, said: “This ranking judges world class universities across their full range of activities — teaching, research, knowledge transfer and international outlook – using Times Higher Education’s trusted, rigorous standards. To emerge as Israel’s number one university and 17th across the entire continent of Asia is a major achievement and something to be celebrated. Hebrew University has shown particular strength in research impact – our analysis demonstrates that its research is pushing the boundaries of knowledge and is being cited globally.”

"The 2016 Times Higher Education Asia University Rankings rank the top 200 universities in Asia, and are based on the same rigorous criteria as the THE World University Rankings – but with special modifications to better reflect the characteristics of Asia’s universities. We judge world class universities employing 13 separate performance indicators across all of their core missions – teaching, research, knowledge transfer and international outlook," according to Times Higher Education.

The Hebrew University of Jerusalem is Israel’s leading academic and research institution, producing one-third of all civilian research in Israel. For more information, visit http://new.huji.ac.il/en.

Hebrew University Ranked #17 in Asia, First in Israel, in 2016 Times Higher Education Asia University Rankings
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