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During cell division, errors made during the distribution of chromosomes to the daughter cells result in cells with an abnormal number of chromosomes, which is called aneuploidy. Aneuploidy is the cause of the majority of miscarriages and is also present in ~90 percent of solid tumors. Paradoxically, aneuploidy is universally harmful to cellular fitness, but can be advantageous to the cells under selective conditions. In the Campbell lab, we study how specific patterns of aneuploid chromosomes are selected for over time and how aneuploidy affects cellular physiology and drug resistance.
Aneuploidy has historically been a very challenging to study as it affects the expression levels of hundreds of functionally unrelated genes simultaneously. To address this challenge, we have developed innovative bottom-up approaches to study aneuploidy including: 1) in vitro evolution methods for observing how aneuploidy patterns develop over time 2) techniques for engineering aneuploidy in both yeast and human cells, and 3) ways of creating partial chromosome amplifications/deletions to determine which parts of chromosomes are primarily responsible for aneuploidy phenotypes. We have developed these methods in both yeast and human cells to facilitate both high throughput and more disease-related research.
Chris Campbell received his PhD in biochemistry and cell biology from the University of California San Francisco. He then conducted a postdoctoral fellowship at the University of California San Diego before forming his own group at the Max Perutz Labs in 2015.
Different cancer types have distinct patterns of aneuploidy that they acquire over time, with some specific aneuploid chromosomes being present in the vast majority of certain cancers. Often, these patterns are very complex, consisting of many different chromosome gains and losses in the same tumor. We have therefore developed methods to observe the formation of complex aneuploid karyotypes over time to determine what factors determine the selection of such patterns. These studies have revealed many basic principles underlying aneuploidy selection.
Aneuploidy is generally bad for the growth and viability of cells due to imbalances in gene expression between chromosomes. It is therefore surprising how frequently aneuploid chromosomes arise as adaptive mechanisms instead of other, more targeted mutations. One reason for this may be that aneuploidy has the ability to alter the expression many different genes at the same time. We have therefore developed methods for systematically analyzing how combinatorial effects of genes lead to strong aneuploidy phenotypes.
Aneuploidy resulting from defects in chromosome segregation during meiosis are the cause of the majority of miscarriages. We are working to uncover novel mechanisms regulating meiotic chromosome segregation to determine what makes this process uniquely error-prone. In addition, we are testing the possibility that meiosis provides a barrier to adaptation via aneuploidy.
Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.
Adell, Manuel Alonso Y; Klockner, Tamara C; Höfler, Rudolf; Wallner, Lea; Schmid, Julia; Markovic, Ana; Martyniak, Anastasiia; Campbell, Christopher S
Adaptation to high rates of chromosomal instability and aneuploidy through multiple pathways in budding yeast.
Clarke, Matthew N; Marsoner, Theodor; Adell, Manuel Alonso Y; Ravichandran, Madhwesh C; Campbell, Christopher S
Aurora B activity is promoted by cooperation between discrete localization sites in budding yeast.
Marsoner, Theodor; Yedavalli, Poornima; Masnovo, Chiara; Fink, Sarah; Schmitzer, Katrin; Campbell, Christopher S
Christopher Campbell is part of the SFB "Meiosis"
The Campbell Group is supported through the "Vienna Research Groups for Young Investigators" program.
The Campbell group participates in in the special Doctoral Program 'Chromosome Dynamics' reviewed and funded by the Austrian Research Fund FWF.