Neuroendocrine tumors (NETs) affect at least 35 people per 100,000 and are often misdiagnosed at first; time from symptom onset to proper diagnosis often exceeds five years. Many physicians and specialists are not aware of current diagnostic and treatment options, and often, NETs that may have been treatable early go undetected until they have metastasized. These tumors originate from cells that release hormones into the blood in response to a signal from the nervous system. They occur most often in the gastrointestinal tract (and occasionally in the lungs or pancreas). For over 50 years, cancer research has been one of the main pillars of scientific endeavor at the Weizmann Institute. Dozens of scientists from a variety of disciplines work tirelessly to uncover the complex mechanisms that govern this deadly disease. Newer areas of interdisciplinary emphasis at the Institute include neuroscience and immunology. Insights from combinations of these fields may be harnessed to inform the design of therapeutic strategies to combat NETs, as well as many other diseases and disorders. The scientists involved in this project, Professors Gil Levkowitz and Irit Sagi and Dr. Itay Tirosh are conducting research of particular relevance to the neuroendocrine function, the central nervous systems, cancer, and NETs. They will no doubt increase our understanding in this important area.

Prof. Elior Peles from the Department of Molecular Cell Biology combines molecular, biochemical, and advanced light and electron microscopy techniques to study myelin, the insulating membrane sheath that enables fast and efficient nerve conduction and supports nerve cell integrity and survival. His research focuses on studying key molecular mechanisms and proteins that mediate the interactions between the axons and the myelinating cells. These proteins are crucial for the correct wrapping of axons with myelin and determine the precise molecular organization of these nerve fibers, which is crucial for their normal function. Better understanding of the mechanisms that control myelination and the organization of myelinated axons may inform the design of new therapeutic strategies for MS and other demyelinating disorders.

The Azrieli Institute for Systems Biology provides a platform for collaboration between various disciplines that, together, are creating new, holistic approaches to characterizing the networks that govern complex interactions within biological systems. From genome architecture and function to model organism development, to the multi-scale dynamics that drive both health and disease, Systems Biology provides a computational framework for understanding life in all its complexity. The Azrieli National Institute for Human Brain Imaging and Research promotes studies related to the physiology, biochemistry, and functioning of the human brain, with the goal of devising improved therapies and, eventually, cures for brain-related diseases. The Azrieli Foundation also supports Prof. Irit Sagi’s research in Fragile X syndrome (FXS). FXS is the most common inherited form of intellectual disability, affecting between 1:4,000 and 1:6,000 individuals and 30% of those are diagnosed with autism. Nevertheless, there is slow progress in understanding the pathophysiology and the development of effective therapies. Prof. Sagi and her team discovered that MMP-9 an enzyme which was identified as a direct therapeutic target in FXS brain disorder was present with elevated protein levels in FXS patients and relevant mice models. Using biophysical and drug design tools Prof. Sagi and co-workers established a novel experimental scheme to design and generate novel anti-MMP9 inhibitors capable of passing the brain BBB. Their on-going work already yielded novel mechanistic insights on FXS initiation and progression.

Prof. Michal Schwartz’s research is focused on the role of innate and adaptive immunity in central nervous system (CNS) plasticity in health and disease, and on developing methodologies to manipulate the immune system to benefit the CNS under acute injuries, chronic neurodegenerative conditions, mental dysfunction, and brain aging. Her team established the pivotal role of the systemic immune system in healthy brain function and repair.

The World Health Organization estimates that 7.4 percent of global years lost to illness, disability, or premature death are caused by disorders in the mental and behavioral disorders category, including depression, anxiety, schizophrenia, and bipolar disorder, among other debilitating conditions. Throughout the world, individuals who suffer from a serious mental illness, in which the ability to function in daily life is significantly impaired, die 10 years earlier than individuals in the general population, on average. Mental illnesses rank as the third costliest medical conditions in terms of overall health care expenditures, behind only cardiac conditions and traumatic injury. As we have known for many years, different people react differently when exposed to the same level of stress, be it biological, chemical, or environmental stress. Some people’s brains successfully adapt and respond in a way that promotes continued vitality and function, leading to resilience; other people’s brains react with maladaptive responses, which can begin with subtle alterations in the genome or epigenome and spiral into post-traumatic stress, anxiety, or substance use disorders, psychosis, metabolic dysfunction, or even death. Understanding such differences in the brain’s ability to compensate for injury and adjust to changes in the environment would clarify the mechanisms governing healthy human behavior and address an urgent public health need. Weizmann Institute neuroscientists are studying how the brain adapts and responds to the stressors of daily life, and how maladaptive neurological responses to these stressors can cascade into mental illnesses.

Prof. Irit Sagi’s ground-breaking cellular research has led to the development of antibodies with therapeutic potential to be used in the treatment of invasive diseases such as cancer and Crohn’s. Merging real-time spectroscopic and molecular imaging techniques, Prof. Sagi was the first to reveal the complex molecular nature of matrix metalloproteinases (MMPs), a group of human enzymes linked to cancer and autoimmune diseases. Insights derived from these studies led her to design a new class of inhibitory antibodies that thwart the negative action of these enzymes. These prototype antibodies are currently being developed for clinical use in inflammatory and cancer diseases. Aiming to highlight the latest advances in MMP research from a multidisciplinary perspective, Prof. Sagi coedited a book on the subject called Matrix Metalloproteinase Biology in 2015. Prof. Sagi continues to develop novel experimental tools to decrypt the extracellular matrix molecular remodeling code at near-atomic resolution in healthy and diseased tissues. Her unique biophysical approach is used to decipher molecular mechanisms of dysregulated break-down of proteins in tissues and to develop a new generation of safe and effective drugs.

World-renowned researchers at the Weizmann Institute of Science are actively investigating cancers of the blood-forming organs. Over half of all life sciences research at the Institute is focused on cancer, and Weizmann’s unique multidisciplinary environment means that collaborative teams armed with the most advanced research tools, as well as with a massive body of institutional expertise, are bringing their considerable resources to bear on the unique problems posed by blood-related cancers.

While finishing her PhD, Dr. Segev read research insights that suggested that there is chemical crosstalk between algae and marine bacteria. She suspected that there might be some critical interaction that—in the absence of bacteria—was not happening in the lab. As a microbiologist, she was aware of the growing number of Microbiome studies showing how bacteria vastly influence their hosts, like bacteria in the human gut. She decided to investigate whether micro-algae have their own “Microbiome” and started by growing algae together with common marine bacteria often found in association with algae blooms. Dr. Segev is currently preparing a more complex model that, like the ocean environment, includes more than one type of bacteria. Examination of complex cultures under various environmental conditions is necessary in order to understand how ambient conditions during Earth’s history have influenced microbial interactions and different paleo-proxies. Dr. Segev’s proposed research will create a bridge between the micro-scale mechanisms of algal-bacterial interactions, the global scale bio-geochemical cycles and the geologic record.