Research

Benjamin Geiger and his group focus mainly on the mechanisms responsible for communication between cells, both normal and cancerous. In doing so, they explore the specific molecules involved in recognition, adhesion, and communication with the extracellular environment, and the signaling triggered by these interactions. Such processes are investigated using diverse biological systems, including metastatic cancer cells, inflammatory cells associated with a variety of diseases, blood platelets, and immune cells.

Senescent cells accumulate in premalignant lesions, sites of tissue damage and in normal tissues during aging. We study how senescent cells affect cancer, aging and age-related diseases and also placenta during embryonic development.
• Cellular senescence in aging and age-related diseases
• Cellular senescence in premalignant lesions and cancer
• Interaction of senescent cells with the immune system
• Cellular senescence during embryonic development

Gil Levkowitz utilizes zebrafish as a vertebrate model organism to tackle basic questions concerning the development and function of the hypothalamus. Hypothalamic neurons regulate fundamental body functions including sleep, blood pressure, temperature, hunger and metabolism, thirst and satiety, stress and social behavior. Understanding these processes is especially important as developmental impairments of hypothalamic neuronal circuits are associated with neuronal circuits that have been associated with neurological conditions such as depression, chronic stress, autism and obesity.
In particular, the lab investigates the molecular and cellular processes underlying morphogenesis and function of hypothalamic neurons that produce the neuro-hormone oxytocin, whose axons project onto the pituitary and form the hypothalamo-neurohypophyseal system.   A primary research direction is studying the assembly and maintenance of the neuroendocrine interface between oxytocinergic neurons and neurohypophyseal vasculature, through which oxytocin is released into the general circulation without disrupting the blood-brain barrier (BBB).  Another major goal is studying how specific hypothalamic circuits regulate stress and social challenges using a set of behavioral assays in fish and mice.

Research in the lab focuses on the biology of Schwann cells and oligodendrocytes, the myelinating glial cells of the peripheral and central nervous system, respectively. We are using a variety of molecular, biochemical and genetic approaches to:  

• Identify the axonal signals that control myelination.
• Understand how glial cells recognize and wrap axon with myelin.
• Dissect the cytoskeletal machinery that drives myelination.
• Reveal how myelinating glia shape the membrane of the axons they wrap.

Our lab studies the molecular mechanisms that regulate, control and execute developmental neuronal remodelling in Drosophila. Remodelling is essential for sculpting the mature nervous systems of both vertebrates and invertebrates during development and when it is perturbed, we think it is a major cause of psychoneurological conditions such as schizophrenia and autism.
We use Drosophila as a model system to study pruning and regrowth during remodelling and our main approach is developmental genetics. The stereotypy of remodeling in Drosophila as well as the wide range of genetic tools available, make it a unique system to dissect the mechanisms of neuronal remodeling in vivo.

While DNA methylation is essential for normal mammalian development, how it regulates and maintains cell fate and function remains largely unknown. To uncover the functional roles of epigenetic dynamics during development and disease we utilize cutting-edge genome- and epigenome-editing tools, sophisticated epigenetic and gene expression reporters, embryonic stem cells and mouse genetics. Specific topics include:

• Mammalian parental imprinting as an epigenetic paradigm
• Genome-wide epigenetic reprogramming during gametogenesis
• DNA methylation dynamics at distal regulatory regions during cell fate changes
• Environmental effects on the epigenome
• Epigenetic perturbations in disease and cancer

The Tirosh lab is studying human tumors as a complex ecosystem in which diverse cancer and non-cancer cells interact and collectively determine tumor biology and response to therapies. We leverage single cell technologies, computational approaches and clinical collaborations to identify important tumor subpopulations such as cancer stem cells, drug resistant cells, invasive cells and immune cells that respond to immunotherapies. We then study the function and regulation of these subpopulations in model systems, with the ultimate goal of developing better cancer treatments.