Integrated Calendar

The understanding of strongly-correlated quantum matter has challenged physicists for decades.
Such difficulties have stimulated new research paradigms, such as ultra-cold atom lattices for
simulating quantum materials. In this talk I will present a new platform to investigate strongly correlated physics, namely moiré quantum matter. In particular, I will show that when two graphene sheets are twisted by an angle close to the theoretically predicted ‘magic angle’, the resulting flat band structure near the Dirac point gives rise to a strongly-correlated electronic system. These flat bands systems exhibit a plethora of quantum phases, such as correlated
insulators, superconductivity, magnetism, Chern insulators, and more. Furthermore, it is possible to extend the moiré quantum matter paradigm to systems beyond magic angle graphene, and I will present an outlook of some exciting directions in this emerging field.

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.