Master of Disaster Management (M.DM.)

Research

Jun 22nd, 2015

Molecular Analysis of Cancer Immunoresistance

Prof. Zvi Fishelson, Ph.D.
Department of Cell and Developmental Biology

The long-term goal of our research is to develop a novel treatment for immune resistant cancers. Our research includes characterization of the mechanism of complement dependent cytotoxicity and of the basis for elevated resistance of cancer cells to cell death, and design of novel reagents that sensitize cancer cells to cell death. Research methods used include analyses of cell growth and death and mitochondrial activity, western blotting, enzyme-linked immunosorbent assay (ELISA), immunoprecipitation, confocal fluorescence microscopy, Fluorescence-activated Cell Sorting (FACS), peptide analysis by mass spectrometry, electon microscopy, and analysis of cancer growth in animal models.

Research

Jun 22nd, 2015

Prof. Neta Erez, Ph.D.
Department of Pathology

The main goal of our laboratory is to uncover stromal pathways that contribute to tumorigenesis and metastasis. In particular, we combine transgenic mouse models of cancer as well as clinical data to study the role of inflammation and cancer-associated fibroblasts in facilitating lung metastasis of breast cancer, and to uncover the role of neuroinflammation mediated by astrocytes in melanoma brain metastasis.

Extensive research has led to the understanding that tumors are more than just cancer cells: stromal cells in the tumor microenvironment play a crucial role in all stages of tumor initiation and progression, and cancer research is no longer focused only on the pathways inside tumor cells, but rather on tumors as multi-cellular organs.

The major cause of cancer mortality is metastasis to distant organs. Currently, metastatic cancers are incurable and available therapies can only prolong life to a limited extent. Therefore, uncovering the mechanisms that facilitate metastasis is an urgent and unmet clinical need. Nevertheless, changes in the metastatic microenvironment that enable the growth of disseminated tumor cells are poorly characterized,
and are the major focus of our research.

Expanding our understanding of the early stages of metastatic growth is an essential prerequisite for the discovery of novel target molecules for the development of targeted therapeutics that may prevent, rather than try to cure, metastatic disease.

Research

Jun 22nd, 2015

PARP Proteins in Health and Disease

Prof. Malka Cohen-Armon, D.Sc.
Dept. of Physiology & Pharmacology and the Neufeld Cardiac Research Institute

The general focus of our research is on signal transduction mechanisms implicating PARP (polyADP-ribose polymerase) proteins. PARPs are highly conserved proteins that are involved in a variety of processes, including epigenetic mechanisms, DNA repair, cell cycle and gene expression. PARP-1, the most abundant PARP protein, is activated by binding to single strand DNA breaks. Activated PARP-1 recruits ligazes to the lesion, promoting DNA repair.

One of our contributions to this field was the discovery of alternative mechanisms activating PARP-1 in the absence of DNA breaks. This unveiled a variety of extra-nuclear signals activating PARP proteins in a variety of processes regulating gene expression.

We found that PARP-1 is a target of signal transduction mechanisms activated by intracellular Ca2+ mobilizition or by the MEK-ERK phosphorylation cascade. Moreover, we found that ERK activity in the nucleus is highly up-regulated by activated PARP-1, implicating PARP-1 in ERK-dependent gene expression. Up-regulation of immediate early genes underlying long-term memory formation may underlie the pivotal role of PARP-1 in long-term memory formation during learning. Regulation of gene expression, controlling cell growth and development, may underlie the role of PARP-1 in neuronal remodeling and cardiomyocytes growth.

Recently, we found that a phenanthrene derived PARP inhibitor acts as an extra-centrosomes de-clustering agent, exclusively and efficiently eradicating human cancer cells by ‘mitotic catastrophe’ cell death, without impairing normal cells. Since many human cancer cells depend on extra-centrosomes clustering for their survival, this molecule is now used for developing a novel cancer targeting therapy.