Director, Goldyne Savad Institute
Hadassah Hebrew University Hospital
Dr. Hilla Giladi Ph.D
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.Our group is studying the expression and the function of microRNAs, mainly of the liver-specific and most abundant - miR-122.
Dr. Jonathan H Axelrod Ph.D
scientist- Team head
Jonathan Axelrod is a staff scientist at the Gene Therapy Institute. Dr. Axelrod has explored the wiles of interleukin-6 (IL-6) in its many roles within processes of tissue injury, repair, and regeneration. His work initially focused on processes of liver injury and regeneration where he used IL-6 as a tool to understand how, in acute hepatic failure, IL-6 promotes metabolic equilibrium and liver regeneration, and, in chronic liver injury, how IL-6 alternatively functions to protect against liver cancer and at times, paradoxically, serves to promote liver cancer.
Daniel Goldenberg is a staff scientist at the Gene Therapy Institute. Dr. Goldenberg is studying the molecular and cellular mechanisms of liver regeneration and development of chronic inflammation-mediated hepatocellular carcinoma using mouse models. His work resulted in determining of multiple regulatory mechanisms that govern the development of hepatocellular carcinoma on the background of chronic liver inflammation. Currently, his research group is exploring regulation of the LINE-1 retro- transposition in hepatocellular carcinoma by microRNAs.
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].
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.
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.
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 PhD student
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 PhD 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 PhD 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.
Shanny Barnoy, BsC student
We are investigating the hormone-like effect of miR-122 which is generated in the liver, is secreted to the blood stream from where it reaches remote tissues in the bodies, and exerts its regulatory effect. We are interested in studying the vehicle responsible for transporting the secreted miR-122 in the blood.
Yamama Abu Mohsen, MSc student
I am working on the project “searching for the regulatory function of miRNAs in liver cancer“. The results are evaluated by different methods (CRISPR-Cas9 system, Antago-miRs, Mimic-miRs) to see the effect of the miRNAs on retrotransposition events and proliferation.
Dana Eidelshtein, a PhD student
We investigate the anti-fibrotic effects of miRNA in the liver. Using bioinformatic tools we found that miR-9 targets the TGF-β pathway. We found that NOX4, which plays a vital role in promoting and preserving fibrosis, is a specific target of miR-9. Using LX-2 cells (human hepatic stellate cells), we treated activated HSCs with miR-9 and miR-122 and successfully decreased fibrosis levels measured by α-SMA signal. Additionally, we have shown that miR-9 is a secreted miRNA in fibrotic cells, and may help us set ground for developing a therapeutical agent against liver fibrosis.
Yael Volman, a PhD student
To combat DNA damage, cells have evolved different strategies, collectively referred to as DNA damage response (DDR). While DDR is essentially a cell-autonomous process that occurs in the nucleus, the cell surface epidermal growth factor receptor (EGFR) has been shown to accelerate DDR. It is known that cell cycle arrest is necessary for effective DNA repair. However EGFR drives cells to cell cycle progression. In my project I am looking for the intersection of this reciprocal communication (the “outside-in” EGFR signal and the “inside-out” nuclear DDR). We show that DNA damage modifies signal transduction triggered by EGFR activation and suggest that these signaling events serve an essential role in synchronizing cell-cycle progression and survival mechanisms. This leads to optimized conditions for cell recovery and DNA damage repair. We hope to provide a plausible explanation for the paradox of this known role played by growth factors such as EGFR in DNA damage repair.
Osher Amran, a PhD student
Pancreatitis is a pancreas inflammation. The most common causes of pancreatitis include gallstones (40%), alcohol abuse (33%), idiopathic (15-25%) and post endoscopic retrograde cholangiopancreatograpy (ERCP) (5-10%). Treatments for pancreatitis are limited and generally supportive. The overall mortality rate in acute pancreatitis is 10-15%. Thus, there is an urgent need for finding a treatment for pancreatitis. According to some recent papers, FGF21 can be a treatment for pancreatitis. In our research, we want to try some FGF21 agonists as a medication for pancreatitis. We will induce pancreatitis in two different known models of pancreatitis in mice and hopefully will cure them with our medications.