Laboratory team members
The laboratory team is comprised of senior research members, undergraduate students as well as visiting students coming for summer or limited periods. As a team we are actively involved and interact continuously with other teams at the Goldyne Savad Gene Therapy Institute. I’m both the Director of the Institute and heads my own team described below, one of the teams in the institute. Our Institute is one large open space enabling direct and continuous interaction between the 10 research groups based within the Institute. [Meital: Here, a picture of the lab open space]. The many technologies and equipment strategically placed and positioned on the lab benches enables easy accessibility to all researchers. This even includes large equipment like confocal microscopy and FACS machines. [A picture of the confocal microscope].
Hilla Giladi, PhD, (Chief of Laboratory)
Hilla is an established molecular biologist and is actively involved in the education of the students and post-docs in the lab. In our research, we need to harness many new methods and technologies, Hilla is also responsible for harnessing all new activity, methods and technologies. She is our cloning Guru and has never failed. She has been a lab member since the establishment of the Institute. Her main force is the education of students guiding them on all techniques of good laboratory practice. Hilla's current main research activity is the role of microRNAs in physiological and pathological processes.
Lina Mizrachi, MSc, Technician
Lina has been working as a technician at the lab for many years. Her research now involves the deciphering of the role of microRNAs in exosomes: She is developing a new technology to extract small RNAs and large RNAs from exosomes and will then perform next generation sequencing to identify the RNA species in these vehicles. She is currently working as a team with the PhD student Tomer Freemann.
Devorah Olam, BSc, Technician
Devorah is our animal farm specialist. She is responsible for the mouse breeding and teaching of students how to work with mouse colonies. She performs the genotyping of the engineered mouse strains we keep for the group studies. Her long-term experience with animal care enables her to be our daily animal farm trouble-shooter.
Orr Levkovitch, BSc, Technician
Orr is investigating the role of chromothripsis and micronuclei formation in the development of hepatocellular carcinoma (HCC). Together with Tali Lanton, another PhD student, she found that IL6 enhances micronuclei formation and chromothripsis. She is presently investigating whether this is dependent on STAT3. This investigation could have clinical implications: Upon partial hepatectomy, a surgical procedure to treat liver cancer, which induces liver regeneration and enhances HCC a potential anti-STAT3 therapy could be beneficial. This is investigated in a model.
Katia Chapchay MD, Post-doc research fellow
Katia is a physician scientist currently conducting her research fellowship. She is a plastic surgeon. Her investigation is in conjunction with the PhD student Mor Paldor. They are investigating the role of skin inflammation in hair loss following radiation. The idea is to translate our findings on the mechanism of hair loss to a clinical study. Together with Prof. Shimon Benita we are developing a cream with specific antibodies to block the pathway inducing the inflammation associated hair loss following radiation.
Nir Rosenblom, PhD – A post-doc
Nir completed his PhD at our laboratory and continued his studies for his 1st post-doc period. Nir investigated the role of Radio-frequency ablation (RFA) on the development of hepatocellular carcinoma (HCC). He found that in the MDR2 KO mouse model of chronic liver inflammation resulting in HCC, RFA is a tumor ablator but at the same time also a tumor inducer. In his studies published in a number of reports he shows that this process is dependent on HGF and on IL6. He is travelling soon to Pasteur for his 2nd post-doc experience.
Rona Harari, a PhD student
Rona is now completing her PhD studies and is travelling to the West Coast (USA) for her next step in science (either in academia or industry). She is investigating the role of miR-675 in liver cancer. She had showed that miR-675, which is derived from the 1st exon of the lncRNA H19, has a necroptosis effect. She is now investigating molecular pathway leading to this phenomenon.
Mor Paldor, a PhD student
Mor is investigating the role of IL6 in radiation induced alopecia. She has dissected the molecular and cellular mechanism of this psychologically devastating clinical condition. She has established the relevant model and through this model, was enable to find the role of IL6 and IL17 in the loss of hair following radiation. Currently she in translating her results into potential therapeutic approaches. Her report on this study was submitted for publication.
Tali Lanton, a PhD student
Tali is investigating the role of IL6 in hepatocarcinogenesis associated with inflammation. She generated a number of engineered mice to dissect the mechanism associated. She crossed the MDR2 KO mice with a hepatocyte specific depleted STAT3, and also crossed the MDR2 KO with an IL6 KO mice, and crossed the sgp130 mice in which IL6 trans-signalling is ablated with the MDR2 KO mice. The surprising finding is that in all these three engineered mice there is an increase in hepatocarcinogenesis, rather than decreased as expected. She is currently investigating the microbiome and other potential contributors to this surprising phenotype.
Alina Simerzin, Graduating PhD student
In her studies Alina had a very unexpected observation which, she developed independently in the lab. She found that the major p53 negative controller MDM2 is targeted by the liver specific microRNA miR-122*. She proved the relevance of this in hepatocellular carcinoma (HCC) growth in vitro and in vivo. This observation was already published in recent months. She then went on to question whether the tumor suppressive effect of miR-122* is only on HCC and found that it is also a tumor suppressive miR on human papilloma virus induced cervical cancer. She dissected the mechanism and found that this is independent of MDM2. Soon, she will submit this finding for publication, again an unexpected finding, which opens a whole new therapeutic avenue (a patent on this finding was also submitted already). Alina will soon move to Harvard University Medical School to the group of Prof. Galit Lahav to investigate the regulation of p53.
Chofit Chai, a PhD student
Non-alcoholic steatohepatitis (NASH) is becoming a world epidemic. Currently there is no real therapy for NASH. NASH is progressing in all western world countries and will become a major health care burden. It will become the primary cause for the development of cirrhosis, HCC and the indication for liver transplantation. Chofit work involved as well as showing the systemic effect of miR122. Her investigation is currently under revision in a leading journal.
Nofar Rosenberg, a PhD student
One of the pivotal question in the field of liver cancer is which cell is the source of the carcinogenic clone. To answer this question, we have crossed the MDR2 KO mice, which on the background of the B6 develops HCC at the age of 14 months, with a which enables lineage tracing of hepatic progenitors (this mouse expressed out of the ROSA locus GFP dependent on Foxl1 (a progenitor cell marker) expression). Currently Nofar is collecting the mice data on HCC and also on the development of cholangiocarcinoma. During the coming year, we will have an answer to our question. During her investigation she also found a new target for miR122 which could explain its tumor suppressive properties and is establishing the results with additional experimental investigations.
Tomer Freemann, a PhD student
The mechanism of hepatic carcinogenesis is largely unknown. One potential mechanism of hepatocarcinogenesis is the activation of retro-elements and their movement in the genome. We are interested to investigate whether miRs could be involved in this process and whether exosomes or large vesicles are delivery vehicles for the retro-elements as LINE from cell to the other, and if there are specific miRs which participate in these processes, as negative or positive regulators. Tomer has already established the needed experimental tools in the laboratory and is now performing in vitro studies to answer these questions.
Aurelia Markezana, a PhD student
Radiofrequency ablation (RFA) is the preferred treatment for some patients with HCC. However, the experience is that following RFA there is recurrence or development of a second primary in the cirrhotic liver following the RFA. Aurelia is interested in understanding the mechanism of this phenotype. In her first stage she is modeling part of the story by asking whether in vitro heated hepatocytes could enhance the tumorigenic phenotype. This she does by applying the medium of heated cells over non-heated cells. She has already observed that hepatocytes following heating secrete pro-tumorigenic factors. Now she is assessing whether the same is also happening in vivo. The dissecting of the mechanism in vivo will enable to assess a therapeutic approach to prevent tumor recurrence. This is a very relevant clinical program.
Dayan Ayaish, a Master student candidate
Nodding syndrome (NS) is a killer of children aged 3-18 in the Horn of Africa. Thousands of children die each year after several years of suffering. Although this disease is associated with Onchocerca volvulus infection (river blindness) and the presence of neurotoxic autoantibodies, the mechanism of disease is not understood. We pioneered the discovery of autoantibody development after other brain infections, including herpes virus encephalitis, and have hypothesized that NS is also an autoimmune malady based on our preliminary results: Patients have a specific cytokine profile; they harbour specific autoantibodies including anti-AMPA GluR3, anti-NMDA-NR1 and -NR2A; these antibodies bind cultured human neurons derived from human embryonic stem cells, and killed by yet unknown mechanisms. The autoantibodies also bind human T cells, and kill a specific population of T cells. Upon administration of purified patient IgG compared to control IgG into mice brains these develop seizures and some die – indicating that the IgG causes this dreadful condition. These initial observations strongly suggest an autoimmune etiology, but much investigation is needed to prove that this is the mechanism. Dayana has initiated her investigation in the institute on this project.
Zohar Shemuelian, a Master student
We have a preliminary result that we have recently reported indicating that miR122 is regulated by TNFa to induce anemia through the regulation of erythropoietin expression. Zohar is investigating two clinical relevant conditions in which TNFa is increasing significantly and is also associated with the development of anemia: Acute Malaria and inflammatory bowel diseases. Zohar is assessing whether in these two conditions the increase in miR122 expression is the cause of anemia.
Lika Gemaiev, a Master student
For many years, we have investigated in our lab the role of the imprinted lncRNA H19 gene in hepatocarcinogenesis. We have published a few reports on the role of H19 in carcinogenesis. There is a debate in the literature whether H19 is a tumor suppressor gene or an oncogene. To answer this question related to hepatocellular carcinoma (HCC) we have generated engineered mice on the background of MDR2 KO in which H19 is ablated. Now we have these mice on the background of B6 and are approaching the age of 14 months, the age in which HCC is expected to develop. Lika is performing this investigation to answer whether in this model H19 is an oncogene or a tumor suppressor. The answer could have translational aspects.
Maytal Gefen, a Master student
Both miR122 and miR122* were reported by ourselves as well as by others as tumor suppressor microRNAs. One model that showed their tumor suppressive effect is the miR122 KO mice. These mice develop NASH and then HCC. However, in this engineered mouse both miR122 and miR122* are ablated. It is hard to determine which of the two is responsible for the phenotype. Maytal is generating genetic tools which enable to identify the contribution to the tumor suppressive effect of each separately. The results again will have significant translational importance.
