Lab research areas
The lab focuses on the study of a rare subpopulation of cancer cells, called persister cells, that can evade therapy through a non-mutational reversible mechanism. The lab combines clinical data, experimental and computational approaches to uncover the basic biology underlying the ability of cells to survive drug onslaught in the absence of a resistance-mediating genetic alteration. They develop new tools and systems to study reversible resistance in hope to pave the way for new therapeutic approaches that could prevent the emergence of genetic resistance.
For her PhD in the Departments of Cell Biology and Molecular Microbiology at Tel Aviv University, Yaara Oren investigated how harmless commensal bacteria evolve to become deadly pathogens. She focused on gene regulation, the process used to control the timing, location, and amount in which genes are expressed. By combining computational analysis of hundreds of microbial genomes with an experimental approach, Dr. Oren and her team showed that bacterial genes can rapidly “switch” between multiple regulatory modes, a previously undiscovered mechanism that may underly the emergence of pathogens. Her work resulted in three publications and was awarded the Proceedings of the National Academy of Science (PNAS) Cozzarelli Prize for Scientific Excellence and Originality in Biomedical Sciences (best paper award), an amazing achievement for a doctoral student.
Dr. Oren’s postdoc research in the Department of Cell Biology, Broad Institute and Harvard Medical School, investigated cancer ‘persisters’, a rare cell population that is highly tolerant to treatment without any underlying genetic cause. She developed a new high complexity tool for monitoring drug-treated cells over time. This study could help uncover what drives non-genetic relapse.
In her tenure-track faculty position at the Faculty of Medicine at Tel-Aviv University, Dr. Oren’s lab applies computational and quantitative experimental approaches – combining microscopy, genetic tools, metabolomics, transcriptomics, epigenomics, drug screening and modeling – to examine the molecular mechanisms that drive “reversible resistance,” which is observed in many cancer patients. They have a favorable initial response to therapy, but then develop recurrent disease and succumb within five years of diagnosis. It is thus urgent to understand how to target these patients in order to prevent treatment failure. Dr. Oren hopes her work will pave the way to more durable and evolutionarily stable anti-cancer treatments.