I am the Director of the only Gene and Cell Therapy Institute in Israel which I established in 1998 at Hadassah Hebrew University Hospital. I also serve as a full professor at the Hebrew University. Since its establishment 19 years ago I have recruited, accommodated and supported 10 seniors, academic track investigators, in the Institute. The Institute's focus is on performing translational medicine research. Today we have 75 investigators in the Institute. We believe in the need to understand the mechanism of disease as an approach to developing new therapeutics. Precision Medicine is our theme in which gene and cell therapy is one executing arm of this approach. In an effort to test our investigative approach and translational avenues I also established a gene and cell therapy production site in which we have developed over 50 products that were tested in Phase I and II. Many of these programs are also making further drug development progress today. Education and teaching is a cornerstone of our institutional culture and I devote much effort and time to this. Our institute culture is based on transparency in the sharing and flow of ideas. Many young Israeli investigators working in laboratories around the country as well as abroad were educated and mentored in our Institute at Hadassah and the Hebrew University Medical School.
As a physician-scientist specialising in Hepatology and Gene Therapy, my main interest lies in deciphering the mechanism of liver disease for the development of new genetic and biologic therapeutics. I focus on Hepatocellular Carcinoma (HCC) and have contributed to a better understanding of the role of inflammatory mediators. I discovered and reported on the role of IL6 in HCC development and on the pivotal role of inflammation in HCC development. I developed numerous therapeutic platforms that were tested clinically or are now in clinical development including: Hyper-IL6 (invented by Prof. Stefan-Rose John with whom I collaborate for > 20 years), siRNA therapeutic scaffold for pancreatic cancer, and microRNAs for cancer therapy e.g. miR122* for cervical cancer. I have 185 refereed papers cited over 8,000 times (without self-citation). I have published in the following leading journals; Nature, Nature Medicine, PNAS, Gastroenterology and Hepatology (I had also been the associate Editor of this leading journal).
- A small animal model for Hepatitis B and C virus (HBV & HCV) infections
- Human monoclonal anti HBV and HCV antibodies that underwent a clinical translation
- Understanding the role of IL6 and IL6 trans-signalling in tissue regeneration
- A siRNA based therapy against pancreatic cancer – currently in phase II clinical studies
- Found the mechanism of inflammation induced anemia – miR122 dependent
- Identified the role of miR122* in HCC development
- Mechanism of radiation induced alopecia, and found a therapy for this
- Mechanism of the “killer” of the horn of Africa, Nodding syndrome: An autoimmune malady
- Role of microRNAs in the development of non-alcoholic steatohepatitis
- Role of IL6 in radiation induced senescence and xerostomia
- Mechanism of HCC development following radio-frequency ablation
- Role of the lncRNA H19 in HCC development
- Developed the oncolytic virus, Newcastle Disease virus for treating Glioblastoma multiforme
- Developed femtosecond ultrafast infrared laser for gene transduction
- Currently developing new drugs for NASH based on our findings of miR-122 in triglyceride metabolism.
Both hepatocytes derived microRNA-122 and microRNA-122*, as others and we show have a tumor suppressive effects. This figure adopted from an editorial (Hepatology. 2016 Nov;64(5):1424-1426) on our report summarizes the known about microRNA 122/122* biogenesis and targets through which tumor suppression is mediated
Figure 2: Upon inflammation TNFα induces microRNA-122 expression and secretion. This microRNA then circulates in the blood stream to reach the cells in the kidney which produce erythropoietin. This microRNA-122 targets the seed sequence of the message of erythropoietin to reduce its expression.
Figure 3: Free fatty acids via RORα induce the expression of microRNA-122. This increase then is followed by microRNA-122 effect inside the liver for the reduction of triglycerides biosynthesis by targeting the 3’-UTRs of two mRNAs of genes involved in triglycerides biosynthesis. The microRNA-122 then is secreted out of hepatocytes to target peripheral cells including adipocytes, muscle cells and heart muscle cells. In these cells, there is also a reduction of triglyceride biosynthesis, and increase in free fatty acids which then reach the liver and hepatocytes through the circulation and complete this “hormonal” type of circle, by inducing moicroRNA-122 increase.
Figure 4: Our team is interested to identify the cell of origin of liver cancer, the hepatocellular cancer. To do this we have engineered a number of mouse models and are now following them. We have found that there is evidence for the origin of a specific type of cancer in the liver that originates from the putative liver stem cell. We are now further investigating this and developing therapeutic approaches.
Productivity in Nature as well as in Biomedical Sciences is dependent on personality (innovative, hardworking, professionalism, knowledge, curiosity, stamina and love to science). We educate to this in our lab and institute.
The most valuable and important asset of any scientific team is the students:
Dr. Hilla Giladi the team leader with our team, PhD students (left to right): Maytal Gefen, Nofar Rosenberg, Alina Simerzin (graduated and left for a lab in Harvard), Chofit Chai and Hilla Giladi.