סמינר מיוחד של החוג לגנטיקה מולקולרית של האדם וביוכימיה

Dept. of Human Molecular Genetics and Biochemistry

החוג לגנטיקה מולקולרית של האדם ולביוכימיה

You are cordially invited to the special seminar of the

Department of Human molecular Genetics and Biochemistry

Sackler Faculty of Medicine

By:

Ofer Shoshani, Ph.D.

Ludwig Institute for Cancer Research, Department of

Cellular and Molecular Medicine,

University of California, San Diego, USA

Title:

“Order from chaos: Chromosome Catastrophes Drive

Cancer Evolution”

Abstract: 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 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. Second, 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. I will conclude by discussing an outlook towards the exciting new directions opened by this work.

The Seminar will take place on

Tuesday, December 1, 2020 at 10:00 AM

via Zoom:

https://us02web.zoom.us/j/83645287656

Meeting ID: 836 4528 7656