Boaz Tirosh

Supervisor ESR9, ESR10

Prof. Boaz Tirosh is a tenured faculty member at the School of Pharmacy of the Hebrew University of Jerusalem, Israel since 2006. Prof. Tirosh is the authors of more than 50 original peer reviewed publications and an inventor of several patents in the field of bioproduction. Before joining the Hebrew University, Prof. Tirosh completed his PhD in Immunology at the Weizmann Institute of Science and fulfilled more than 5 years of postdoctoral training at Harvard Medical School (MA, USA). The main scientific interest of the Tirosh laboratory is the unfolded protein response (UPR) in the immune system and in the liver. Prof. Tirosh identified molecular interactions of the UPR and cell metabolism in various models, including drug induced liver injury.  In 2014-2015, Prof. Tirosh spent a sabbatical at the cell line development unit of Bristol Myers Squibb (NJ, USA) in which he developed novel technologies for improved protein expression.

The lab is funded by grants from the Israel Science Foundation, Israel Cancer Association and the Israeli Ministry of Science and Technology.

Our lab is interested in understanding the roles of the unfolded protein response in immunity, cancer and drug metabolism. In the course of TREATMENT we will explore, using mouse and cellular models deficient for UPR elements, the roles of the UPR in the dyslipidaemia caused by anti-schizophrenic drugs. In addition we will study the effect of these drugs on the immune system in the liver and using immune-deficient animals, we will establish whether the immune system affects drug metabolic outcomes. The two elements, UPR and immune system, will be integrated to identify biomarkers that are associated with drug adverse effects.

1. Lab personnel

  • Naresh Kumar, postdoc
  • Viviana Scaiewitz, PhD student
  • Akram Obiedat, PhD student
  • Mohammed Mahamid, PhD student
  • Odai Darawshe, M.Sc. student.

2. TREATMENT project

  • ESR9

    ESR9 will evaluate Drug-induced activation of the Unfolded Protein Response (UPR) in the liver in order to explore the effects of olanzapine/aripriprazol on ER stress signalling in the liver and whether mitochondrial UPR is activated by the drugs; to find molecular connections between drug catabolism and ER stress responses in the liver in vitro and in vivo. The ESR will aim to delineate molecular interconnectivities between drug catabolism and the extent of UPR (PERK, ATF6, IRE1α) in the liver. This will be achieved by testing the drug effects in the ER stress responses in genetically modified hepatocytes by CRISPR/Cas9 editing followed by the study of their metabolic responses. Animals with liver specific impaired UPR will be evaluated.

  • ESR10

    ESR10 will study the effects of antipsychotic drugs in the immune system in order o characterize alterations in the immune system in schizophrenia and following olanzapine/aripriprazol treatment. The ESR will examine the direct effect of the antipsychotic drugs on immune cell activation in vitro in co-culture settings, as well as the secondary response of the immune system to hepatic drug catabolism in vivo. The lymphocyte/macrophage infiltration into liver and adipose tissues following antipsychotic treatment will also be evaluated in animal models of schizophrenia as well as metabolic dysfunctions. Considering the association between the immune responses with obesity and metabolic adaptations, we should establish the cause-effect relationships between the innate and chronic immunity with drug induced metabolic dysfunctions using mice that are immunodeficient.

3. Links