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Research

Our research is concentrated on the regulation of processes responsible for the concerted action of cells, tissues, and organs. Studies are conducted in the field of signal transduction, development, system biology, imaging and fertility. More detailed information on our studies is described here.

Nava Dekel

The control of reproduction

Oocytes in the ovarian follicles are arrested at the first meiotic division. Meiotic arrest persists until the onset of puberty when at each reproductive cycle, some oocytes progress to the second metaphase and arrest again. Meiosis is completed upon fertilization. The early embryo travels along the oviduct to develop into a blastocyst, which enters the uterus for implantation.
Current studies in our laboratory are directed at understanding the mechanisms underlying the control of reproduction with a focus on:

  1. The ubiquitin-proteasome pathway in oocytes resuming meiosis
  2. Vasorin in ovarian physiology
  3. Angiogenic events in ovulating follicles
  4. The immune system in ovulation
  5. Implantation-associated Inflammation.

Ayelet Erez

Cell metabolism in health and disease

The Erez group focuses on deciphering the dynamic changes in cells’ metabolism in health and at different disease states. More specifically, we are interested in understanding the role and contribution of the urea cycle enzymes and their intermediate metabolites to specific cellular phenotypes. The metabolic analysis is performed with unique equipment including gas chromatography mass spectrometry which allows analysis of dynamic flux between different metabolic cycles. Using in vitro and in vivo techniques, we combine basic molecular methods with genetic mouse models to gain insights to metabolic aberrations that accompany human disease process with an attempt for translational therapeutic relevance. 

Atan Gross

Apoptosis Metabolism

The major research topics of the Gross lab evolve around how mitochondria act as “headquarters” to coordinate
metabolism and apoptosis with a special emphasis on a novel mitochondrial protein named Mitochondrial Carrier Homolog 2 (MTCH2). Our research topics focus on the role of mitochondria in 1) stem cell biology (hematopoietic stem cells and embryonic stem cells), 2) skeletal and heart muscle biology, 3) brain biology. One of our recent findings demonstrates that priming mitochondrial function triggers stem cell mobilization in the bone marrow.

Ami Navon

Protein degradation by the ubiquitin/proteasome system

The proteasome is important for immune system, a key factor in the inflammatory response, and in generating peptides used for MHC class I presentation. Currently, our lab is investigating three aspects related to proteasomal degradation. The major effort of the lab is invested in understanding the molecular mechanism underlining the function of the proteasome regulatory ATPase complex, which is responsible for substrate recognition, unfolding and translocation into the 20S proteasome. This includes mechanistic reasons for the failure of the 26S proteasome to degrade certain substrates under specific physiological conditions. To address these scientific aims, we use an integrative approach of biochemistry, structural biology and cell biology.

Michal Neeman

Vascularization during pregnancy and cancer development

The vascular bed is essential for survival of all multicellular organisms larger than a millimeter. Accordingly, all changes in the structure and function of tissues, in health and disease, are accompanied by vascular changes. The aim of our work is to map the regulatory network controlling growth and function of blood and lymphatic vessels. For that aim, we develop novel multi-modal imaging tools that allow us to obtain dynamic information on critical checkpoints of vascular remodeling. Our research is focused on one hand on maternal vascular remodeling during pregnancy and on the other hand on vascular development in ovarian carcinoma.

Irit Sagi

ECM remodeling: from biophysical principles to drug design

“Thinking outside the cell.” Our group develops and uses novel tools to study extracellular matrix (ECM) functional remodeling and proteolysis within a sub-cellular microenvironment in tissues. Our desire is to unravel key molecular mechanisms by directly observe native ECM-remodeling at multiple scales approaching fine molecular, near atomic detail. The mechanistic insights derived from our integrated multidisciplinary research strategy leads to the design of new therapeutic and diagnostic agents for treating ECM related inflammatory and cancer diseases.

Rony Seger

Intracellular signaling cascades

The intracellular transmission of extracellular signals mediates and regulates essentially all stimulated cellular processes. In the lab, we study the effect of seven intracellular signaling pathways in the induction of cellular processes. One of the hallmarks of intracellular signaling is the translocation of the signals to the nucleus, via nuclear translocation of signaling proteins.  We are currently elucidating the unique mechanism of stimulated nuclear translocation, which regulates proliferation and differentiation. This process is important as a regulatory step in the regulation of stimulated transcription, and its specific prevention serves as a new tool in combating cancer and other diseases.

Amos Tanay

Genome and epigenome regulation

The Tanay group is developing new strategies for understanding genome and epigenome regulation in heterogeneous cell populations. This is done by combining single cell genomics approaches, techniques for studying chromosomal conformations, and data-driven models for quantitative gene regulation. The group is particularly interested in applying such techniques to understand the evolution of tumor heterogeneity and how it affects cancer biology and treatment.

Igor Ulitsky

lincRNA function

Protein-coding DNA sequences account for less than 2% of the human genome. Recent studies found that the long stretches of DNA located between the protein-coding genes are pervasively transcribed into different classes of RNA molecules including long intervening non-coding RNAs, or lincRNAs. Our lab takes an interdisciplinary approach that combines experimental and computational tools to study the functions of these RNAs, the principles that dictate their mode of action, and the consequences of their disruption in human disease.

Karina Yaniv

The development of the vascular system

The development of the vascular system is one of the earliest events in organogenesis. All other organs depend on a vascular supply for delivery of nutrients, oxygen, and for clearance of wastes. Serious disruptions in the formation of the vascular network are lethal early in post-implantation, while the maintenance of vessel integrity and the control of vessel physiology have important consequences throughout embryonic and adult life. In recent years, it has become clear that many of the signals implicated in embryonic vascular development are reactivated during disease states of angiogenesis such as tissue ischemia, coronary heart disease and cancer-promoted angiogenesis. This has further reinforced the potential medical relevance of vascular development studies such as those carried out in our laboratory.

Yossi Yarden

Growth factors and their receptors in cancer

Tumor progression is driven by collaborative interactions between genetic aberrations intrinsic to tumor cells and a plethora of host factors, such as the tumor’s stroma. While intercepting the deleterious effects of genetic aberrations presents remarkable pharmacological challenges, therapeutic manipulations of tumor-stroma inter- actions appear more feasible. Hence, we employ two arms: on the one hand we study the effects of growth factors and their receptors on cell proliferation and the acquisition of metastatic capabilities. The other arm develops biomolecules able to block the action of growth factors and their receptors. Currently, the exploratory arm focuses on inositol lipid phosphatases, actin and tubulin binders, as well as non-coding RNAs, whereas the therapeutic arm develops aptamers, decoy receptors and oligoclonal antibody mixtures.

Hadassa Degani

Professor Emeritus

The research in our group explores the progression of cancer including hormonal regulation, the development of blood vessels - angiogenesis and metabolism using molecular and physiological characterization by means of non-invasive magnetic resonance imaging and spectroscopy. The studies are conducted in human breast, prostate and lung cancer cell cultures and tumors in animal models. In addition, clinical investigations of breast, prostate and lung cancer patients were performed by means of MRI and CT. Specific efforts are directed to develop and improve the magnetic resonance imaging and spectroscopic methods quantifying spatial changes with time. With these methods we were able to characterize flow and permeability limited perfusion, water and contrast agent diffusion, convection and the disparity in perfusion due to interstitial fluid pressure. We also developed means to monitor choline and glucose metabolism including transport and intracellular conversion and established the molecular basis for the alteration of these processes by malignant transformation. Recently MRI sensitive probes which specifically bind to the estrogen receptor were designed in collaboration with professor D. Milstein (Organic Chemistry). These probes are utilized as molecular imaging biomarkers for localizing and quantifying the estrogen receptor.

Yoram Salomon

Professor Emeritus

The major subject of research in the lab deals with Vascular Targeted Photodynamic Therapy (VTP). This novel anti cancer treatment modality was developed in the last 15 years in collaboration with Professor Avigdor Scherz from the Department of Plant Sciences at the Weizmann. The treatment comprises of i.v infusion of Pd-bacteriochlorophyll based photosensitzers synthesized in the A. Scherz laboratory with concomitant illumination (760nm) of the target tumor for 15-20 minutes via interstitial optic-fibers. The cytotoxic superoxide & hydroxyl radicals locally generated, induce vacular damage (blood cloting and vasoconstriction) that block blood supply to the tumor within minutes, leading to focal tumor ablation within days and to healing within weeks. Only a single treatment session is required and drug clearance from the circulation is completed within minutes, circumventing patient's skin photo-toxicity. In preclinical studies we showed that the success rates of VTP in mice and rats are high (50-90%) and in case of failure a 2nd treatment can be delivered with increased success rate. Tumor response and healing are associated with extensive immune response and with development of tumor resistance that may be applied in future long term therapy. Magnetic resonance imaging (MRI), based on photochemical generation of in-situ paramagnetic deoxyhemoglobin contrast was developed for online follow up of VTP progress. Clinical trials for therapy of prostate cancer and age related macular degeneration in collaboration with Steba Biotech are in progress.
A novel direction of treatment based on photodynamic ablation of a selected rat embryo as model for the treatment of ectopic pregnancy was recently reported.

Alex Tsafriri

Professor Emeritus

The elucidation of several mechanisms involved in oocyte maturation, including the differential regulation of phosphodiesterase expression that allows resumption of meiosis; and the involvement of ovarian proteolytic enzymes (tPA, plasmin, and collagenases), their inhibitors (PAI-1, and TIMP-1), eicosanoids and other paracrine regulators in ovulation.