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Jacob Scott (Cleveland Clinic)

Date: Thu. April 19th, 2018, 4:00 pm-5:00 pm
Location: Rockefeller 301

Learning to perturb the evolutionary mechanisms driving drug resistance in cancer and microbes: an integrated theoretical and experimental approach.

The evolution of resistance remains an elusive problem in the treatment of both cancer and infectious disease, and represents one of the most important medical problems of our time. While the illnesses are different on several non-trivial levels including timescale and complexity, the underlying biological phenomenon is the same: Darwinian evolution. To comprehensively approach these problems, I have focussed my attention on building a broad suite of investigations centered around the causes and consequences of the evolutionary process in these contexts. I will discuss my and my collaborator’s efforts to; model the evolutionary process on the genomic scale in both an analytic (Markov process) and stochastic (individual based model and inference) format; to quantify in vitro competition and interaction between cancer cell lines through an evolutionary game theoretic lens using time-lapse microscopy and computer vision; and to understand the evolutionary contingencies inherent in collateral sensitivity in E. coli and ALK mutated non-small cell lung cancer.
 
References
 
I will present results from several published and unpublished works, including:
 
Collateral sensitivity networks reveal evolutionary instability and novel treatment strategies in ALK mutatted non-small cell lung cancer: https://www.nature.com/articles/s41598-017-00791-8
 
Steering evolution with sequential therapy to prevent the evolution of bacterial antibiotic resistance: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004493
 
Collateral sensitivity is contingent on the repeatability of evolution. https://www.biorxiv.org/content/early/2017/10/11/185892
 
Fibroblasts and alectinib switch the evolutionary games that non-small cell lung cancer plays https://www.biorxiv.org/content/early/2017/09/20/179259
 
 
Page last modified: April 13, 2018