Research Department of Immunity, Microbiology and Inflammation
The Research Laboratory Counter-Parasitic Diseases of Associate Professor Ankri Serge.
Entamoeba histolytica is an intestinal parasite responsible for amebiasis. Approximately 50 million people have invasive disease annually resulting in 100,000 deaths per year making it the second most common cause of parasitic death in humans. The vegetative stages (trophozoites) of E. histolytica live in the large intestine and form encysted stages (cysts) that are excreted with feces. The trophozoites can penetrate into the intestinal wall and invade the liver and other organs to produce clinical forms of amebosis, most frequently intestinal amebosis and hepatic amebosis (amoebic liver abscess). The infection is transmitted by cysts from one human to another due to transmission of mature cysts with foods (fruit vegetables) and drinking water contaminated with fecal material. Inside its human host, the parasite is challenged by various stressful conditions that originate in part from the immune system of its human host (like the production of nitric oxide by phagocytes). The main goal of our laboratory is to understand the role of epigenetic processes in controlling the adaptation of the parasite to environmental stresses.
The Regulation of Gene Expression lab of Professor Choder Mordechai (Motti).
Research in our lab focuses on the cross talks between all stages of gene expression. We therefore study transcription, mRNA export, translation and decay. We focus on unraveling the mechanisms that integrate all these stages into a system, using “classical” molecular biology, whole cell and bioinformatic approaches.
In recent years, studies of single genes have evolved into analyses of network of genes to obtain a whole-genome view. We have initiated an analogous zooming out on molecular processes, thus shifting gene expression from studies of distinct processes (e.g., transcription, translation) to investigating how all these processes are interconnected and integrated in a manner that enables the cell to function as a system. We have proposed novel concepts, mRNA coordinators, mRNA imprinting, and synthegradases, that helped us obtain a “bird eye” view.
The Laboratory Investigating the Immunological Basis of Cancer and Autoimmune Diseases of Professor Karin Nathan. which focuses on exploring the mechanistic basis of immunological tolerance in the context of three different models of autoimmune diseases: Multiple Sclerosis (MS), Inflammatory Bowel Diseases (IBD) and type I diabetes. Its particular interest is in regulatory T cells. The lab also investigates the role of chemokines, small proteins secreted by immune cells to attract others, in autoimmune diseases and cancer. As for cancer diseases, its major focus is on understanding how chemokines drive the recruitment of bone marrow derived cells to support tumor development and angiogenesis.
The Molecular Virology Laboratory of Associate Professor Tamar Kleinberger. Research in the lab focuses on virus-host cell interactions and on the use of viral proteins for induction of cancer-specific cell death. Specifically, the lab currently studies the mechanisms involved in the ability of the adenovirus E4orf4 protein to inhibit the DNA damage response, a cellular network that identifies DNA damage and transmits signals that promote its repair. This system serves as an antiviral defense mechanism and must be neutralized to improve virus replication. The lab also investigates how E4orf4 and its cellular partners (in particular protein phosphatase 2A and chromatin factors) induce cell death. Understanding these mechanisms may provide an explanation for the cancer specificity of E4orf4-induced cell death and may, in the long run, suggest novel targets for cancer therapy.
The Yeast Genetics Laboratory of Associate Professor Kornitzer Daniel.
We investigate the pathogenic yeast Candida albicans, a prevalent cause of life-threatening infections in immunocompromised patients. We study the adaptations that turned this organism into a successful invader of patients’ blood and tissues, and focus, at the molecular level, on two of its pathogenic characteristics in particular. One is the ability of this fungus to utilize hemoglobin as an iron source, by relying on a newly identified family of extracellular heme-binding proteins. The second is its ability to switch from the yeast morphology to the more invasive mold morphology, and how this switch can be inhibited, i.a. via the activity of the ubiquitin system.
The Developmental Immunology and Aging Laboratory of Professor Doron Melamed. which focuses on studying mechanisms controlling generation of normal B-lymphocytes and B cell malignancies, to understand how cellular pathways that include signaling molecules, transcription factors and microRNAs operate during B cell development and control crucial fate decisions of normal and transformed B cells. The lab is specifically interested in finding how sensitivity and resistance to cell death signals are regulated in these cells. An additional topic of interest is in investigating how homeostatic mechanisms control B lymphopiesis in general, and particularly in aging, though attempts to identify cross-talk mediators between peripheral B cells and progenitors in the bone marrow that can be targeted to restore immune competence in aging.
The Systems Immunology and Precision Medicine Laboratory of Assistant Professor Shai Shen-Orr. Research in the lab is focused on studying immune system variation and differences, abundant from the single cell to the whole organism level. Research projects in the lab study how single cell differences effect the immune response of a cell population or changes in response between individuals. From a clinical standpoint, research in the lab pursued towards increased understanding of how immunity is orchestrated in man and to apply this knowledge towards advancing genomic medicine.
The Immunotherapy Laboratory of Assistant Professor Miki Rahat studies the interactions between macrophages and tumor cells in cancerous diseases, and between macrophages and inflamed tissue cells in autoimmune diseases. We explore the mechanisms that allow tumor cells to reprogram infiltrating macrophages to become pro-angiogenic and pro-metastatic and promote tumor growth. We focus on EMMPRIN/CD147, a multifunctional protein that is overexpressed in many types of tumor cells, which mediates such interactions and regulates angiogenesis and metastasis. We study how EMMPRIN is regulated, how it regulates the tumor microenvironment, and how to inhibit tumor growth and dissemination by targeting EMMPRIN with specific antibodies or by active vaccination. Additionally, we explore how EMMPRIN contributes to the pathophysiology of autoimmune diseases, such as rheumatoid and psoriatic arthritis.
The Sleep and Psychoneuroimmunology Laboratory of Assistant Professor Asya Rolls.
Research in the lab focuses on the interaction between the emotional state and physical well-being. Using state of the art tools in neuroscience and in immunology the lab studies the neuronal basis of brain-immune communication, and in particular on two major aspects of brain activity; first, how does sleep and sleep disorders affect the immune system and second, how neuronal networks involved in positive emotions alter the ability of the immune system to fight infections and cancer.
The Immune Cell Signaling, Migration and Cancer Laboratory of Assistant Professor Debbie Yablonski. Immune cells are remarkable for their extraordinary sensitivity to antigen, coupled with extreme selectivity. The lab studies the molecular regulatory mechanisms that underly this behavior, to explain how immune cells are able to mount potent responses to minute quantities of foreign antigens, while ignoring related “self” antigens. This question is studied in T cells, the central arm of the cellular immune system, and in mast cells, an important mediator of allergy. Within the cells, tightly regulated signal processing mechanisms are employed to integrate and interpret information about the presence of antigens, resulting in a cellular decision about how to respond. Specialized signaling proteins, known as adaptors, play an essential role in this process, and are the focus of the lab’s research. A variety of genetic approaches, including mouse models and somatic cell genome editing techniques, are used by the lab to explore the ways in which adaptor proteins fine tune immune sensitivity and selectivity.
The Sleep Medicine laboratory of Professor Lavie Peretz.