לוח שנה משולב

Chromosomal instability is one of the major hallmarks in cancer driving numerical and structural chromosome aberrations. Cancer cells can use the chaotic background of chromosome instability to generate ordered genomic events leading to accelerated tumor formation or drug resistance. First, I will discuss how transient centrosome amplification can induce a burst of chromosomal instability in vivo. This triggers the formation of random aneuploidies (changes in chromosome numbers) with cancer initiating cells carrying a specific aneuploidy signature leading to accelerated tumorigenesis. This work has uncovered aneuploidy as a direct driver of cancer and enables a better understanding of the involvement of specific aneuploidies in cancer. Second, I will describe how chromothripsis, the catastrophic shattering of a chromosome and random religation of its pieces, can promote resistance to therapy. Using cancer cells and patient samples, I identified that chromothripsis drives the formation and evolution of extrachromosomal DNA (ecDNA) elements that can amplify genes conferring drug resistance. Chromothripsis depends on non-homologous DNA end joining repair, a vulnerability that could be exploited for therapeutic purposes by preventing resistance to chemotherapy. I will conclude by discussing an outlook towards the exciting new directions opened by this work.

With increased life expectancy, the incidence of patients suffering from Alzheimer’s disease (AD) and dementia has been steadily increasing. Currently, there is not a single treatment that can change the diseases course. Our team, over more than two decades, has demonstrated that the brain needs support from the immune system for its life-long functional plasticity and repair. Furthermore, using immunological and immunogenomic tools, we demonstrated that in AD, the immune system dysfunctions and perpetuates the pathology. Based on these observations and numerous others, we proposed that boosting the systemic immune system might facilitate mobilization of immune cells to help the brain. We found that the optimal way to activate such a reparative immune response is by reducing the restraints on the immune system, by blocking the PD-1/PD-L1 inhibitory immune checkpoint pathway. This therapy facilitates translocation of phagocytic cells to the brain; based on their transcriptomic profile, we demonstrated that these cells express molecules that can uniquely remove the toxic forms of misfolded proteins plaques, dead cells, and cell debris, and can thereby rescue synapses, change the disease course and improve brain function. Overall, our results indicate that targeting systemic and local immune cells rather than brain-specific disease-escalating factors provides a multi-dimensional disease-modifying therapy for AD and dementia, regardless of the primary disease etiology. Our approach is under an expedited development process towards clinical trial.

The Israel Directorate of Defense Research & Development (DDR&D; מפא״ת), which is best known for orchestrating the development of the Iron Dome, joined the Ministry of Health in the fight against the COVID19 pandemic from its beginning. Corona Forum 876 of the DDR&D is an scientific body created to consult and cooperate with the DDR&D, the Ministry of Defense, Ministry of Health and others in the fight against corona. It consists of several professional groups, composed of experts from the academia, health system and industry. Several activities of Forum 876 and the DDR&D, including corona testing, immunization and swab pooling will be described.