Research Department of Biochemistry
The Lipid Research Laboratory of Professor Aviram Michael, focuses on the mechanisms involved in macrophage cholesterol and lipids accumulation, and in foam cell formation under oxidative stress, the hallmark of early atherogenesis, which lead to atherosclerosis development and its consequent cardiovascular (CVD) events.
The cellular and molecular mechanisms behind macrophage – mediated oxidation of lipoproteins (LDL and HDL), as well as that of polyphenols – rich dietary antioxidants (such as pomegranate punicalagin, red wine catechins, licorice glabridin, olive oil hydroxytyrosol, and date phenolic acids) are studied in our lab.
Finally, we analyze the anti atherosclerotic effects, and the mechanisms of action, of serum HDL- associated paraoxonase 1 (PON1) , and that of macrophage PON2, as well as PONs regulation by dietary and by other exogenous and endogenous means.
The Developmental Biology Laboratory of Associate Professor Bengal Eyal. In mammals, it is well established that several factors secreted in the somite environment initiate the myogenic program that is characterized by the activation of two muscle regulatory factors (MRFs), Myf5 and MyoD. Although the MRFs are essential for the establishment of muscle cell precursors and their differentiation, little is known about the intracellular signals that activate their expression in the proper time and place during development. We have been investigating several signaling cascades, such as those of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinases (PI3-kinases), involved in cell growth and differentiation. We found these pathways are involved in different aspects of cell cycle, cell survival and differentiation in tissue culture models of myogenesis. Our goal is to understand the function of these pathways in muscle formation during embryo development and in the destruction of adult muscle tissue that occurs in muscular dystrophies and in chronic diseases leading to muscle cachexia. The role of these pathways during muscle development will be studied in the frog Xenopus laevis and their possible role in muscle disease will be investigated in mouse models.
A second topic being studied is early patterning in the frog Xenopus laevis. We have identified signaling pathways and transcription factors that function in the specification of different germ layers and the patterning of the embryo. These are being studied in great detail that will enable to decipher the earliest events in embryogenesis.
Overall, our studies should broaden our understanding of the principal mechanisms regulating patterning and normal development of skeletal muscles as well as their regeneration in disease and aging.
The Redox Biology Laboratory of Associate Professor Benhar Moran, which focuses on studying the mechanisms whereby redox modifications of cysteine residues regulate protein and cell function.Research projects in the lab use cutting-edge proteomic and biochemical tools to explore the roles of protein redox modifications (such as cysteine nitrosylation) in cellular communication, inflammation, and cancer.
The Molecular Mechanisms of Parkinson’s Disease Laboratory of Associate Professor Englender Simone. Parkinson disease (PD) is one of the most common neurodegenerative diseases and is characterized by Lewy bodies, abnormal aggregates of proteins inside brain cells. One focus of research in my laboratory is to characterize the deregulation of a-synuclein degradation in PD, which underlies its toxic accumulation in Lewy bodies. We have shown that monoubiquitination by the E3 ubiquitin-ligase SIAH promotes the proteasomal degradation of a-synuclein, whereas deubiquitinated a-synuclein is degraded by autophagy. Deubiquitination is modulated by the deubiquitinase USP9X and therefore this enzyme represents a novel therapeutic target. A second line of our research is focused on delineating the mechanisms involved in mitochondria homeostasis in PD. We recently discovered that parkin interacts with a novel substrate, AF-6, which regulates parkin translocation into mitochondria, parkin ubiquitin-ligase activity and mitophagy. AF-6 soluble levels are decreased in PD brains, suggesting that decreased AF-6 levels may contribute to the accumulation of dysfunctional mitochondria in PD. Modulators of AF-6 represent potential therapeutic candidates for PD treatment.
The Molecular Embryology Laboratory of Associate Professor Frank Dale. My research group studies the initial generation of the body axis occurring during embryonic development. Using amphibians as a model vertebrate system, we investigate the cross-talk between transcription factors and signaling pathways to determine how they induce neural and mesodermal cell fates along the body axis during early embryo development.
Frogs, like people, are vertebrates, and the regulation of early embryonic development in all vertebrates (including mammals) is carried out by the same gene products regardless, of species. Thus, the frog (Xenopus laevis) is an excellent system to learn how all vertebrates make their body plan. One of the earliest and most dramatic events in early development is the formation of the body axes. As early embryos, we all start out as a round egg cell, which then rapidly divides into groups of cells. These early stem cells are totipotential and can develop into all cell types of the embryo. At a critical stage, cells commit to specific fates. The cells start migrating, and they elongate to make our typical body plan: the head – tail axis (anterior – posterior), the back – stomach axis (dorsal – ventral) and finally the left – right axis. Cells must know what they are doing along theses body axes. Not only must a cell decide its own identity, a decision to be muscle, blood or nerve for instance. Cells must also define their position along the axis. In the nervous system for example, a cell in the anterior-head makes a forebrain-derived neuron or an eye cell, whereas a nerve cell in the posterior-tail region makes a motor neuron. This location-dependence of cell fate is based on the capability of cells to monitor their position with respect to the developing embryonic axes. In my lab, we are working on the genetic and cellular interactions determining how progenitor like stem-like of the early mesoderm and nervous system acquire these different axial cell fates during early development.
The Laboratory of Vascular Medicine of Professor Levy Andy. Our research is focused on role of the Haptoglobin genotype in determining susceptibility to diabetic vascular complications (cardiovascular disease and renal disease). The lab has a broad translational research program from the bench to transgenic models to the bedside in human clinical trials aimed at understanding the mechanism for the association of the Hp genotype with diabetic complications and how these diseases can be prevented.
The Transport Proteins Research Laboratory of Assistant Professor Lewinson Oded.
Main Research Area: 1. Molecular mechanisms of ABC transporters. 2. Development of Novel Antibiotics to combat multi-drug resistance. 3. Structural studies of membrane proteins. 4. Architecture and function of complex transport systems
Calcium Signaling Laboratory of Assistant Professor Palty Raz. Calcium ions are central and ubiquitous intracellular signaling entities. Changes in intracellular calcium levels control fundamental cellular events, from signaling the mitotic birth of a new cell to marking its end during apoptosis. To generate calcium signals, cells rely on an elaborate machinery of ion transport proteins that are strategically positioned in the plasma membrane (PM) and intracellular organelle membranes. The function of calcium transport proteins at these sites is critical for numerous physiological processes including synaptic transmission, muscle contraction, and the immune response. Consequently, several disease states arise due to dysfunction of calcium transport mechanisms including neurological disorders, cardiac disease and immunodeficiency. Our main focus in the Palty lab is to elucidate molecular mechanisms that regulate calcium signaling across the PM, endoplasmic reticulum (ER) and mitochondria with the long-term goal of understanding how calcium signals are generated at these sites under normal physiological conditions and in disease states.
Translation Regulation and Ribosome-associated Laboratory chaperones of Assistant Professor Shalgi Reut. We are fascinated by the cross-talk between two critical systems in the cell, which thus far were mostly considered as separate:
• Protein synthesis – primarily the ribosome,
• Protein Folding – i.e. Molecular chaperones
It is emerging that molecular chaperones dynamically interact with ribosomes, and that this dynamics is regulated in stress. Also, we found that the association of chaperones with the ribosome is not only for the purpose of folding the newly synthesized protein, but can also mediate translational control. This is a completely new type of cross-talk between the two systems, but the underlying mechanisms are still a very much unknown.
Our lab is looking at networks of chaperones and co-chaperones and their interconnection with the ribosome, and more broadly – the translation machinery, and mapping how they are dynamically regulated. We are also exploring the ways that molecular chaperones mediate translational control during conditions of stress and disease.
Our lab is using cutting-edge high-throughput technologies: Ribosome footprinting, and robotic LUMIER protein-protein interaction assays, together with computational biology and molecular approaches to venture into the mystery of the new roles of ribosome-associated chaperones in controlling translation and coordinating protein homeostasis under challenging environments.
The Protein Quality Control Laboratory of Assistant Professor Stanhill Ariel.
Main Research Area – Cellular adaptation to protein misfolding.
The Molecular Neuroscience Laboratory of Professor Wolosker Herman. Research in our laboratory focuses on understanding the roles of unconventional neurotransmitters, like the D-amino acids in the central nervous system. We are particularly interested in the regulation of N-Methyl- D-aspartate receptors (NMDARs) by D-serine, a D-enantiomer previously thought to be restricted to bacteria or lower invertebrates. D-Serine is now increasingly appreciated as a major physiologic ligand for NMDARs that mediates NMDAR synaptic responses and neurotoxicity both in vitro and in vivo. In addition to neurotransmission, NMDARs play a key role in neurodegeneration, with their excessive activation contributing to neuronal death in several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Over the past few years, we elucidated the mechanisms of D-serine synthesis by the enzyme serine racemase and discovered novel pathways regulating D-serine production and release from neural cells. We also discovered that D-serine is the dominant NMDAR co-agonist mediating neurotoxicity, raising the possibility that drugs that curb D-serine synthesis or release might be useful in neurodegenerative diseases involving NMDARs over-stimulation.
We use molecular biology, biochemical and cell biology techniques in tissues and cell culture models. We generate and keep new mouse genetic models of brain transporters and metabolic enzymes, and also apply neurobiological techniques both in vitro and in vivo.