The Concern Foundation Laboratories
The Lautenberg Center for Immunology and Cancer Research
In the first study, the researchers found that the protein APOBEC3G (A3G) helps repair DNA double-strand breaks and can even rescue mice from lethal doses of radiation. This protein is also involved in nucleotide excision repair and homologous recombination DNA repair pathways. These findings suggest that inhibiting A3G could increase the sensitivity of tumor cells to genotoxic treatments.
In the second study, transgenic mice expressing A3G were able to survive lethal doses of radiation, while wild-type mice did not. A3G was also found to promote error-free repair of DNA damage. These findings have important implications for cancer treatment – inhibiting A3G may make genotoxic therapies more effective, while increasing A3G activity may help protect against radiation exposure.
Models for participation of A3G in DNA damage repair. (A) (DNA) double-strand break repair pathways. (B) UV-damage repair: (B1) GG-NER; (B2) transcription-coupled UV damage repair; (B3) topoisomerase I-mediated NER-independent UV damage repair.
This award recognizes Professor Friedman’s exceptional contributions to the field of computational biology, particularly in the development of machine-learning techniques for analyzing human genomes in the medical field. His pioneering work, which has allowed for highly sensitive measurements of DNA fragments in blood samples and has been widely cited in scientific research, has helped pave the way in the emerging field of personalized medicine.
In the article, the researchers found that the protein WWOX may play a key role in the development and progression of pancreatic cancer. When WWOX was deleted in mice, it led to the formation of precancerous lesions and pancreatic cancer. Overexpression of WWOX in human pancreatic cancer cells reduced their aggressiveness in both lab and animal studies. These findings suggest that WWOX may be a promising target for pancreatic cancer treatment and may lead to new and improved treatment modalities.
Fig. 1: Wwox deletion synergies with KrasG12D activation by accelerating neoplastic lesions formation. (A) Illustration of KWC mice generation, Ptf1a-CreER mice were crossed with Rosa26-LSL- tdTomato to generate WT mice. WT mice were crossed with Kras+/LSL-G12D mice to generate KC mice. KC mice were crossed with (Wwoxf/f) mice to generate either KWC or WC mice. (B) Immunofluorescence of tdTomato (magnification, ×40), immunostaining of WWOX and pERK respectively in KWC, and WT mice (magnification, ×20).
In the three articles, published back-to-back, the researchers specify the need to study chronic inflammation related immune suppression, and show how robust chronic inflammation can be performed in-vivo. They later elaborate on different methodologies to evaluate the related immune suppression using various in-vivo and ex-vivo immunological assays.
Figure 4: Immunofluorescence images showing the distribution of myeloid-derived suppressor cells (MDSCs) stained with the pan-MDSC marker Gr-1 (green) in the spleens of control (A) and inflamed (B) mice. Evident is the morphology of T (red) and B (orange) zones within the spleen and MDSCs surrounding these structures.
In the paper, the researchers profile single cells of adenoid cystic carcinoma tumors, and reveal the transcriptional characteristics of two malignant cell types – myoepithelial cells and luminal epithelial cells. Computational analysis reveals paracrine interactions between the myoepithelial cells that express Notch ligands DLL1, JAG1, and JAG2 which activate the Notch pathway in the luminal cells, supporting their oncogenic growth.
Figure 2D: Heatmap shows expression of the top 200 genes in each of the four NMF programs detected in an individual representative sample. Key genes are annotated on the left, and inferred cell identity is shown on the top.
Prof. Wolf developed a unique method to study viral infection mechanisms of respiratory tracts, which enables the study and further development of new potential anti-viral therapies.
𝐀𝐟𝐭𝐞𝐫 𝐬𝐮𝐦𝐦𝐞𝐫 𝐯𝐚𝐜𝐚𝐭𝐢𝐨𝐧 𝐚𝐧𝐝 𝐭𝐡𝐞 𝐡𝐨𝐥𝐢𝐝𝐚𝐲𝐬, 𝐰𝐞’𝐝 𝐥𝐢𝐤𝐞 𝐭𝐨 𝐬𝐡𝐚𝐫𝐞 𝐟𝐞𝐰 𝐠𝐫𝐞𝐚𝐭 𝐞𝐯𝐞𝐧𝐭𝐬:
𝟏. 𝐓𝐡𝐞 𝟐𝟎𝟐𝟐 𝐝𝐞𝐩𝐚𝐫𝐭𝐦𝐞𝐧𝐭𝐚𝐥 𝐑𝐞𝐭𝐫𝐞𝐚𝐭 included the awarding of the James Sivartsen Prize – click here for more info and photo gallery https://lautenbergcenter.org/the-lautenberg-center/annual-retreats/
𝟐. 𝐓𝐡𝐞 𝐈𝐌𝐑𝐈𝐂 𝐜𝐨𝐧𝐟𝐞𝐫𝐞𝐧𝐜𝐞 𝐚𝐧𝐝 𝐓𝐡𝐞 𝐑𝐚𝐛𝐛𝐢 𝐒𝐡𝐚𝐢 𝐒𝐡𝐚𝐤𝐧𝐚𝐢 𝐀𝐰𝐚𝐫𝐝 𝐨𝐟 𝟐𝟎𝟐𝟐: https://lautenbergcenter.org/the-lautenberg-center/shai-shaknai-award/
3. We were very honored to have had 𝐂𝐎𝐍𝐂𝐄𝐑𝐍 𝐛𝐨𝐚𝐫𝐝 𝐦𝐞𝐦𝐛𝐞𝐫 𝐉𝐨𝐡𝐧 𝐂𝐚𝐫𝐫𝐨𝐥𝐥 and his brother visit our department and labs: https://lautenbergcenter.org/john-carroll/
𝟒. 𝐓𝐡𝐞 𝐋𝐚𝐛 𝐢𝐧 𝐭𝐡𝐞 𝐒𝐩𝐨𝐭𝐥𝐢𝐠𝐡𝐭: come and meet Dr. Oren Parnas’ lab members!
Meet Ph.D student Anastasia Komissarova 🙂
https://lautenbergcenter.org/spotlight-on-oren-parnas-lab/
𝟓. 𝐓𝐡𝐞 𝐝𝐞𝐩𝐚𝐫𝐭𝐦𝐞𝐧𝐭𝐚𝐥 𝐰𝐞𝐞𝐤𝐥𝐲 𝐬𝐞𝐦𝐢𝐧𝐚𝐫𝐬 𝐚𝐫𝐞 𝐛𝐚𝐜𝐤! Join us every Tuesday!
https://lautenbergcenter.org/seminars/
𝟔. The Lautenberg faculty researchers, lab managers, and administrative staff went together for a (half) day in the 𝐌𝐚𝐡𝐚𝐧𝐞𝐡 𝐘𝐞𝐡𝐮𝐝𝐚 𝐦𝐚𝐫𝐤𝐞𝐭! They started in a French cooking workshop where they all showed off their cooking skills, followed by a culinary tour in the market and, exhausted but happy, returned back to work: https://lautenbergcenter.org/gallery/lautenberg-faculty-day-2022/
In the article, the researchers investigated the mucosal susceptibility and immune response to Omicron as compared to Delta and earlier SARS-CoV-2 variants of concern (VOCs). They found that the replication of the Omicron variant in lung tissues is highly restricted when compared to other VOC, whereas it remained relatively unchanged in nasal tissues. Omicron also induced a much stronger immune response compared to earlier VOCs. Their data provides new insights into the reduced lung involvement and clinical severity of Omicron.
Fig 1: SARS-CoV-2 Omicron and Delta replication kinetics in human nasal and lung tissues
Prof. Friedman uses innovative computational biology techniques to study chromatin and gene regulation.
We also like to congratulate Prof. Friedman and his team for their recent publication in Nucleic Acids Research! In their study, the researchers showed how cells regulate the balance between mRNA production and degradation.
Figure 1a:cDTA-seq and genome-wide transcript half-life estimation.
Fig 1: Schematic representation of the growth conditions and media of the NK-92 and growth progression in the media.
In the article, they found that Natural Killer (NK) cells play a role in the immune response against Candida albicans, a common fungal pathogen and a prevalent cause of deadly bloodstream infections. They also found that the fungal cells can inhibit NK cells and that by blocking the NK-fungi inhibitory interaction, using immunotherapy with a TIGIT-blocking antibody, they can re-establish anti-Candida immunity. This discovery can hopefully serve as a potential therapeutic tool in the future.
Figure 2.C. albicans binding of TIGIT is functional and leads to inhibition of NK and T cells.
The Kaye Innovation Awards are given to inventors from the Hebrew University who solve real-world problems by translating scientific excellence into successful commercial ventures. Prof. Aqeilan developed a unique delivery method for gene therapy in WWOX-related human neurological diseases. PhD student Avanthika Venkatachalam from the Ben Neriah lab will receive the award for targeting cancer vulnerabilities in acute leukemia.
The James Sivartsen Prize in Pediatric Cancer Research is awarded each year to a Hebrew University graduate student who is doing the most innovative work with application to the field of pediatric cancer research. During her PhD in the lab of Professor Ofer Mandelboim, Batya published 3 research papers and 2 scientific reviews, studying Urinary Tract Infection biology and treatment modalities.
In the article, the researchers aimed to identify prognostic biomarkers of CMV-related fetal brain injury and identified two amniotic fluid proteins that could be employed in the clinical setting to profoundly improve the prognostic assessment of CMV-infected fetuses.
Figure 4. Amniotic fluid chemerin (A) and Gal-3BP (B) levels in fetuses with severe cCMV (SCC), sensorineural hearing loss (SNHL), asymptomatic cCMV (ACC), and in uninfected fetuses
Joyce was among the pioneers who funded Concern Foundation back in the 1960s. She was an ardent supporter of cancer research at the LRC for more than five decades. She was a unique character that inspired the community of the Concern Foundation and the many young researchers supported by Concern grants. Senior LRC Faculty and staff remember with gratitude her site visits together with members of the Powell Family, her questions, ideas, and warm words of support. We shall miss Joyce, as well as her friendship and leadership.
Our hearts are united today with Rick, Debbie, Nancy, Mike, Linda, and their families. May we be comforted in the eternal legacy of love and compassion that epitomized the meaningful life of our dear Joyce.
In the article, the researchers identify and characterize two cell populations that contribute to bone loss during chronic inflammatory diseases.
“Our findings suggest a central role of inflammatory osteoclast precursors in (iOCPs) bone loss initiation. iOCPs can serve as potential biomarkers for inflammatory bone loss (IBL) detection, and possibly as new therapeutic targets to combat IBL in a wide range of inflammatory conditions.”
Figure 2b: Representative 3D modeling from femoral microCT scans of control (cont.) and inflamed (inf.) mice.
In the article, the researchers study changes in T cells water mass during cell activation and growth.
Our work provides a method to analyze cell water content, as well as insights into the ways cells regulate their water mass.
Figure 2: T cell growth is associated with a gradual decrease in wet to total volume ratio in the early phase followed by a rapid increase in wet to total volume in the late phase.
In the article, the researchers report the synthesis of 3 novel CBG derivatives, which carry anti-inflammatory and analgesic properties.
We believe that HUM-223, HUM-233 and HUM-234 have the potential for development as novel drug candidates for the treatment of inflammatory conditions, and in the case of HUM-234, potentially for obesity where there is a huge unmet need.
Figure 6: Anti-obesity evaluation of HUM-234 (25 mg/kg) in comparison to CBG (15 mg/kg), HFD (high fat diet) and STD (standard food diet).
Dr. Elsana, a member of Prof. David Naor’s team, who was accepted to Teva’s National Forum for BioInnovators program! He was selected as one of 31 top post-docs from Israeli academic institutions. Included in this program, he will also receive from a grant of $10,000 to support his research.
Well done!
This fascinating paper describes a receptor-binding domain fusion protein that neutralizes SARS-CoV-2 infection!
“In this study, we showed that a single ICV injection of AAV9-Syn1-WWOX in Wwox-null neonates rescues the phenotypes associated with WWOX deficiency including growth retardation, hypoglycemia, hypomyelination, seizures and premature lethality.” says Prof. Aqeilan. “Additionally, treated mice were fertile and exhibited normal behaviour” he added.
This proof-of-concept preclinical assessment provides hope for WOREE and SCAR12 syndrome patients. In this context, the Aqeilan lab would like to thank all the patients, their families, and WWOX Foundation for their continuous support and inspiration.”
They weren’t done there; further congratulations are due to Prof. Naor and his team for receiving a prestigious Ines Mandl Research Foundation grant!
We are pleased to invite you to attend the open meeting of the General Assembly of the Israel National Academy of Sciences, which will feature the reception of new members and their inaugural lectures.
Among the new members to be inducted at the ceremony is our own Prof. Yinon Ben-Neria.
The event will take place on the third night of Hanukkah: Tuesday, November 30, 2021, between 18: 45-15: 30, and will be broadcast live on the academy’s website.
To receive a viewing link, we would be very grateful for your registration as soon as possible in the form found in the attached link (each participant must register separately).
You are all welcome,
Lautenberg Center for Immunology and Cancer Research
The exciting program, with leading state-of-the art speakers and students from all over Europe, put an emphasis on SARS-CoV-2. Discussions included neutralizing antibody responses to SARS-CoV-2 variants, vaccines, other viral agents, antiviral vaccine vectors, and vaccine development against SARS-CoV-2.
In addition to SARS-CoV-2, other viral infections were also well-represented, including intrinsic restriction factors to HIV and herpesviruses (including CMV), innate immune resistance hubs, NK cells, trained innate immunity, and mucosal immunity.
The meeting was a great success with outstanding invited talks, excellent student presentations (including open presentation of unpublished data), and exceptional audience participation with in-depth discussions about each talk.
Due to current regulations we limited the onsite registration to 70 participants, which turned out to be a perfect size for close scientific interactions.
A fascinating and intriguing review on the putative homeostatic role of cancer mutations is published by Prof. Yinon Ben Neriah, Prof. Eli Pikarsky, and PhD student Avanthika Venkatachalam. In this review the authors discuss the potential constructive role of driver mutations in maintenance of tissue homeostasis, and whether they are linked to augmented stem cell renewal – possibly reflecting an adaptive protective mechanism.
The Kaye Innovation Awards are given to inventors from the Hebrew University who solve real-world problems by translating scientific excellence into successful commercial ventures.
In their research, Prof. Berger and Dr. Saragovi used a unique mouse model to examine T-Cell antiviral responses in mice which were kept under low oxygen conditions.
Using molecular, pharmacological, and genetic methods they showed that T-Cell failure to respond under hypoxia stems from mitochondrial biogenesis arrest.
They then demonstrated that hypoxia-arrested T cells in-vivo could be rescued by short exposure to atmospheric oxygen conditions.
Their findings allow for a better understanding of viral infections in hypoxia-associated diseases, and may have clinical implications in the future treatment of such infections.
Beautiful picture by PhD Student Or Reuven of Prof. Michal Baniyash’s lab, showing immune cells localized together in response to a developing tumor.
Prof. Lotem and Dr. Hajaj have discovered that two splice variants of the SLAMF6 receptor are found on human T Cells. While one form has a known antagonist role, the other form acts as an agonist that contributes to the anti-tumor response of T Cells.
They show that promoting mRNA splicing, resulting in an elevated expression of the agonistic form as opposed to the antagonistic one, improves human T-Cell capacity to inhibit human melanoma in mice.
This yin-yang relationship of SLAMF6 splice isoforms may represent a balancing mechanism that could be exploited to improve cancer immunotherapy.
The researchers reveal SARS-CoV-2 tissue and virus-specific innate immune responses of human nasal-mucosal and lung tissues.
“The study sheds light on the role of the nasal-mucosa in active viral transmission and immune defence, suggesting a window of opportunity for early interventions, in contrast to the restricted innate immune response in early SARS-CoV-2 infected lung tissues which could underlie the unique uncontrolled late phase lung damage of advanced COVID-19.”
Dr. Einat Seidel led this exiting work into a new role for a human cytomegalovirus derived signal peptide which is slowly cleaved, enabling it to function in immune evasion! Click here to read more about this important and impressive discovery.
Dr. Yotam Drier was awarded 1.5 million euros from the European Research Council (ERC). The ERC grant will support the Drier lab’s quest to understand epigenetic and topological alterations in cancer and their intratumoral heterogeneity. These efforts include both uncovering fundamental mechanisms that regulate epigenetics and topology, as well as translating these findings to improve treatment of specific cancers, by combining advanced experimental techniques with cutting edge big data analysis. For more information see Dr. Drier’s lab page
The International Birnstiel Award for Doctoral Research in Molecular Life Sciences which awards up to 6 PhD students worldwide! This prestigious prize was awarded to Dr. Kadosh for his work published in Nature earlier this year.
Dr. Kadosh conducted his doctoral research in the lab of Prof. Yinon Ben-Neriah, and his hard work led to the discovery of a novel tumor suppressive activity of mutant p53 in the intestine. Excitingly, it was also shown that this activity was impeded by gut bacteria, thus demonstrating the involvement of the microbiome in tumor development.
This prize is a great honor, and we are very proud of Dr. Kadosh’s achievements!
Their fascinating and important research applies single cell RNA-seq to uncover important players in the early development of pancreatic cancer, a disease with shockingly low survival rates. For more about their valuable discoveries click here.
In the article, Prof. Ben-Neriah and his team show that mutant p53 has an oncogenic effect in the distal gut but a tumor-suppressive effect in the proximal gut, and these opposing properties are determined by the gut microbiome.
Watch a Youtube video review of the project by Eleanor Sheekey
Moreover, the Lautenberg Center is proud to now have two of our professors as members of such academies, with Prof. Rami Aquilan being an Israel Young Academy member.
Professor Dov Sulitzeanu, who is one of the founders of the Lautenberg Center and the Department of Immunology is 100 years old and we at the Center give him our warmest greetings and appreciation for building our Center. Dov has been a role model of a scientist for many of his students and colleagues, including group leaders at the Center. Talking to Dov at his birthday I learned that he follows closely the scientific progress of the Center labs and, as always, raises interesting questions and ideas. As such, Dov continues to be a great source of inspiration to the Center’s members and we all wish him many more happy years. Prof. Yinon Ben-Neriah
To our teacher and my long-standing friend Dov, wishing you many years of gratification and fruitful productivity. Prof. Moshe Kotler.
To my rabbi and mentor Dov, I will never forget your dedicated guidance and wisdom as you mentored me throughout my doctoral studies. Prof. David Naor
Remarkably, three out of the five recipients are members of the Lautenberg Center, and we take pride in their achievements. The Kaye Innovation Awards are given to inventors from the Hebrew University who are solving real-world problems by translating scientific excellence into successful commercial ventures.
Download the Kaye Brochure 2020
The grant will provide support for the next five years for multiple efforts in the Drier lab to systematically uncover how epigenetic alterations drive liver cancers. In addition the ISF will help establish the new Drier lab by supporting advanced experimental equipment and high-end computational infrastructure in a separate new faculty equipment grant.
The company raised over $15M in the financing round pending milestones achievement
Thanks to these efforts the throughput of tests of asymptomatic populations at the Hadassah Medical Center increased more than 7-fold, allowing efficient screening of healthcare personnel and nursing homes. This approach can be easily implemented in other clinical labs and drew worldwide attention.
In the article, Dr. Saleh Khawaled and Prof. Aqeilan show the role of the tumor suppressor WWOXs and its therapeutic potential in antagonize metastasis.
Dr. Oren Parnas and Dr. Yotam Drier collaborate and use their labs’ resources and advanced techniques to study the coronavirus tissue distribution during infection period, and to study the regulation of the human receptor that allows viral entry to cells. These may lead to novel detection and treatment approaches against SARS-CoV-2.
The Lautenberg center for immunology and cancer research
Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University of Jerusalem
POB 12272, Jerusalem 91120, Israel
Tel: 972-2-6757725
Fax: 972-2-6430834
