Department of Immunology & Regenerative Biology

The proteasome is one of the major degradation machineries in eukaryotic cells overseeing the controlled removal of short-lived, damaged, misfolded or otherwise obsolete proteins. Our lab studies the structural and functional mechanisms by which the proteasome and other molecular machines such as p97 recognize and process target substrates. We employ an integrative approach, which include cellular biochemistry, Cryo-EM, organic chemistry as well as MHC class I antigen presentation techniques in our research.

We study human neurodegenerative disease processes and how involved proteins adopt pathological amyloid conformations. To this end, we develop and employ Nuclear Magnetic Resonance (NMR) methods to follow the formation of toxic protein structures directly in live cells. We complement this approach with correlative microscopy routines to arrive at a comprehensive understanding of cellular events that trigger human amyloid diseases.

Adhesion to the extracellular matrix or to neighboring cells regulates multiple cellular processes such as tissue formation, and cell migration, proliferation, gene expression and survival. In our lab, we study the mechanisms whereby cells sense the chemical and physical properties of external surfaced, interpret this information and develop a coherent and robust response. Towards this goal we combine molecular perturbation approaches with advanced, quantitative imaging technologies, to study cell-environment interaction in a wide variety of systems such as cancer invasion, bone homeostasis, epithelial barrier function and T-cell stimulation lymphocytes.

Immune cells exit blood vessels near sites of inflammation using specific combinations of traffic signals. Using different in vivo microscopy approaches in genetically manipulated mice and chambers which simulate blood flow, we dissect how trafficking molecules promote leukocyte exit and which of these signals can also be used by circulating tumor cells during metastasis. We also investigate how specific adhesion molecules expressed by antigen presenting cells and the immune synapses  promote immune cell differentiation and effector functions.

We study the extracellular matrix (ECM) – a tissue-specific, organized structure of secreted molecules providing microenvironmental support and communication network. Dysregulated ECM remodeling enzymes (MMPs, ADAMs, LOX) impair ECM integrity and cellular function, associated with spectrum of diseases. We aim to decode these ECM-related modulations and utilize them as biomarkers of various diseases.  Moreover, an integrated multidisciplinary approach allows us to design new selective and specific inhibitors, which show potential as diagnostic tools and drugs for malignancies, degenerative diseases, and chronic inflammatory conditions.

The vascular bed is essential for survival of all multicellular organisms that are larger than a millimeter. Accordingly, all changes in the structure and function of tissues, which occur in health and disease, during development or degeneration, are accompanied and often induced by vascular changes. The aim of our work is to map the regulatory network controlling the growth and function of blood and lymphatic vessels. Novel MRI tools, accompanied by advanced optical modalities, allow us to non-invasively obtain dynamic information on activity of multiple steps in the angiogenic process and thereby improves our understanding of the key regulatory elements and critical checkpoints of vascular remodeling. Identifications of these checkpoints can be used as targets for intervention, and assist in pre-clinical and clinical development of such novel targeted therapies.

Regenerative biology is an emerging field of research aimed at improving health by repairing or regenerating cells, tissues and organs. Although we know quite a lot about how cells adopt their fate, we know little about how different cell types are coordinated in space and time to generate and regenerate organs and organisms. In our lab, we aim to understand the particular roles that the vascular system plays in these processes. Blood and lymphatic vessels serve not only as simple conduits for oxygen, nutrients, antigens and proteins, but, in fact, play active roles in organ growth, regeneration and aging by modulating cell proliferation, immune responses, the progression and resolution of inflammation, tissue repair, fibrosis and more.

During the past decade our lab has used the zebrafish to study different aspects of blood and lymphatic vessel formation. In particular, we take advantage of the superb abilities of the zebrafish to regenerate most of its organs, to characterize the cellular and molecular mechanisms underlying the involvement of the vasculature in these processes. Our discoveries have greatly contributed to our understanding of the interactions of blood and lymphatic vessels with their microenvironment, and the crucial roles the vasculature plays in organ homeostasis, disease and regeneration.

Macrophages form a body-wide network of myeloid immune cells devoted to homeostasis maintenance and immune defense of the organism. We study these cells and their progenitors in physiology and pathophysiology using gene expression and epigenome profiling, as well as a combination of conditional mutagenesis, in vivo cell imaging, cell ablation and cell transfer strategies. Current focus is given to monocytes, and macrophages in the gut and brain. Specifically, we use small animal models to investigate contributions of these cells to inflammatory bowel disease and the role of microglia and perivascular brain cells in neuro-inflammation and -degeneration.

The lab of host-pathogen genomics is interested in how individual encounters between host and pathogenic bacteria can ultimately define the outcome of infection. This is achieved by applying cross-disciplinary single-cell analysis platforms that collectively enable us to extensively profile and precisely monitor host-pathogen interactions within the context of in vivo infections.

Protein-coding DNA sequences account for less than 2% of the human genome, yet the long stretches of DNA located between the protein-coding genes are pervasively transcribed into different classes of RNA molecules including long non-coding RNAs, or lncRNAs. 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, the consequences of their disruption in human disease, and the ways to target their activity in the clinic. We study lncRNAs in variety of experimental systems, including pluripotent stem cells, cancer cell lines, and mouse models.

Prof. Arnon group's currently focuses on two pathologies of the central nervous.

With Dr. Rina Aharoni: Multiple Sclerosis (MS)

Research of different aspects of multiple sclerosis as they are manifested in various animal models. Uncovering pathological processes, as well as therapeutic immunomodulatory and neuroprotective routes, in particular the mechanism of action of glatiramer acetate (GA, Copaxone), the FDA approved drug developed in her Lab. The group showed that significant repair processes occur in the CNS, and they are upregulated by GA treatment.

With Dr. Ruth Maron: Alzheimer’s disease

The interaction between Amyloid precursor protein (APP) and Tau is important in the induction and/or progression of Alzheimer’s disease. Our group demonstrated that APP and Tau proteins are capable of binding to each other. Nasal administration of a mixture of APP and Tau peptides reduces brain plaques formation, decreases soluble A-beta 1-42 in the brain and significantly improves the cognitive function in an Alzheimer’s animal model. We are continuing this project by testing whether treating the mice with a larger peptide combining between the APP and Tau peptides has an effect on cognition and plaque reduction.

The gut is a complex ecosystem in which epithelial, immune, stromal, neuronal, and microbiota interact at a steady state. Our lab is interested in understanding the immunological features of the gut cells and mainly studies epithelial-immune-microbiota interactions at single-cell resolution. We study these interactions in health and disease by utilizing imaging, genetics, and genomics of gut organoids, mouse models, and human-derived samples. We focus mainly on understanding how the epithelial cells of the gut sense and react to various insults occurring at infection, or diseases, such as inflammatory bowel disease, food allergy, and cancer.

Mutations and growth factors collaborate during progression of cancer and metastasis. In-depth understanding of this collaboration offers therapeutic opportunities. Likewise, we are interested in resistance to drugs targeting the mutations and specific growth factors relevant to tumour progression.

Extracellular signals are transferred from the membranes to the genes in the nucleus via several communication lines known as intracellular signaling pathways. We are studying the regulation of some of these pathways, and concentrate mainly on the subcellular localisation of their components. We recently showed that shuttling of one signaling component to the Golgi is important for the induction of mitotic Golgi fragmentation. Most importantly, we also identified the mechanisms of nuclear translocation of other components and showed that their prevention serve as a potent way to prevent cancer and inflammatory diseases. More studies on the mechanism that govern the regulation of localisation may lead to the development of therapeutic drug for these and other diseases.

Immune cells exit blood vessels near sites of inflammation using specific combinations of traffic signals. Using different in vivo microscopy approaches in genetically manipulated mice and chambers which simulate blood flow, we dissect how trafficking molecules promote leukocyte exit and which of these signals can also be used by circulating tumor cells during metastasis. We also investigate how specific adhesion molecules expressed by antigen presenting cells and the immune synapses  promote immune cell differentiation and effector functions.

The gut is a complex ecosystem in which epithelial, immune, stromal, neuronal, and microbiota interact at a steady state. Our lab is interested in understanding the immunological features of the gut cells and mainly studies epithelial-immune-microbiota interactions at single-cell resolution. We study these interactions in health and disease by utilizing imaging, genetics, and genomics of gut organoids, mouse models, and human-derived samples. We focus mainly on understanding how the epithelial cells of the gut sense and react to various insults occurring at infection, or diseases, such as inflammatory bowel disease, food allergy, and cancer.

The Abramson lab is broadly interested in understanding how immunological tolerance to self is established in the thymus and how breakdown of this process results in autoimmunity. The main lab’s interests include: thymus biology, thymic epithelial cells, the Autoimmune regulator (AIRE) gene, autoimmune disorders, immunotherapy, innate lymphoid cells, etc.

We study the extracellular matrix (ECM) – a tissue-specific, organized structure of secreted molecules providing microenvironmental support and communication network. Dysregulated ECM remodeling enzymes (MMPs, ADAMs, LOX) impair ECM integrity and cellular function, associated with spectrum of diseases. We aim to decode these ECM-related modulations and utilize them as biomarkers of various diseases.  Moreover, an integrated multidisciplinary approach allows us to design new selective and specific inhibitors, which show potential as diagnostic tools and drugs for malignancies, degenerative diseases, and chronic inflammatory conditions.

The vascular bed is essential for survival of all multicellular organisms that are larger than a millimeter. Accordingly, all changes in the structure and function of tissues, which occur in health and disease, during development or degeneration, are accompanied and often induced by vascular changes. The aim of our work is to map the regulatory network controlling the growth and function of blood and lymphatic vessels. Novel MRI tools, accompanied by advanced optical modalities, allow us to non-invasively obtain dynamic information on activity of multiple steps in the angiogenic process and thereby improves our understanding of the key regulatory elements and critical checkpoints of vascular remodeling. Identifications of these checkpoints can be used as targets for intervention, and assist in pre-clinical and clinical development of such novel targeted therapies.

Protein-coding DNA sequences account for less than 2% of the human genome, yet the long stretches of DNA located between the protein-coding genes are pervasively transcribed into different classes of RNA molecules including long non-coding RNAs, or lncRNAs. 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, the consequences of their disruption in human disease, and the ways to target their activity in the clinic. We study lncRNAs in variety of experimental systems, including pluripotent stem cells, cancer cell lines, and mouse models.

Metabolic regulation of hematopoietic stem cell migration and development by their dynamic bone marrow (BM) microenvironment and BM neutrophil activation and recruitment. The role of daily circadian light and darkness onset, ROS, nitric oxide, lactate, mitochondria transfer, the endothelial BM/Blood barrier, TNF, Norepinephrine, Melatonin, CXCL12/CXCR4 interactions, pro-inflammatory Thrombin/PAR1 interactions, anti-inflammatory aPC/EPCR/PAR1 stem cell regulation, clinical stem cell mobilization, homing and repopulation are currently investigated.

Mitochondria are highly dynamic organelles that play fundamental roles in pivotal cellular processes including energy production/metabolism, calcium homeostasis, and apoptosis. In our lab we are specifically interested in understanding how these different mitochondrial processes are regulated/coordinated to determine the fate of our cells. Many of our studies are focused on a novel mitochondrial protein named MTCH2 that acts as a receptor for the pro-apoptotic BID protein. Interestingly, conditional knockout of MTCH2 in several different mouse tissues results in significant alterations to mitochondria function and structure leading to changes in cell fate and disease outcome. A better understanding of MTCH2’s mechanism of action will likely uncover hidden connections between the many functions of mitochondria.

We study how epigenetic deregulation in cancer contributes to tumor initiation and progression. To address these fundamental questions, we develop and apply innovative cutting-edge single-molecule and single-cell technologies.

The activity of genes and regulatory elements is modulated by their cell type-specific chromatin organization. Histone modifications and chromatin regulators play important roles in cellular differentiation and development. Chromatin structure is constantly changing in response to developmental and environmental cues; this dynamic regulation is the basis for cellular plasticity.

Disruption of epigenetic control is a frequent event in disease, and specifically in cancer. More than 50% of human cancers harbor mutations in enzymes that are involved in chromatin organization. We develop methodologies at the interface of genomics and proteomics, with the goal of paving the way towards deeper understanding of chromatin regulation, as well as develop novel diagnostic tools for early detection of cancer.

Macrophages form a body-wide network of myeloid immune cells devoted to homeostasis maintenance and immune defense of the organism. We study these cells and their progenitors in physiology and pathophysiology using gene expression and epigenome profiling, as well as a combination of conditional mutagenesis, in vivo cell imaging, cell ablation and cell transfer strategies. Current focus is given to monocytes, and macrophages in the gut and brain. Specifically, we use small animal models to investigate contributions of these cells to inflammatory bowel disease and the role of microglia and perivascular brain cells in neuro-inflammation and -degeneration.