Centriole Amplification The Lab of Greg Rogers Amplified Centriole

Greg Rogers
Greg Rogers' Lab

University of Arizona

Dept. of Cellular and Molecular Medicine

Primary Research Interests:

I. Regulation of Centriole Duplication

Errors in chromosome segregation during cell division can result in the production of aneuploid daughter cells. This is particularly devastating during development, as aneuploidy is an underlying cause of miscarriage, birth defects, and cancers. During cell division, the accurate transmission of replicated chromosomes depends on the assembly of a bipolar spindle which is facilitated by the presence of centrioles, tiny organelles that help generate and organize spindle microtubules. Normally cells contain a single centriole pair, each duplicating only once prior to entering cell division. However, these mother centrioles have the capacity to assemble multiple daughters simultaneously. If cells assemble excess daughter centrioles (known as centriole amplification), then multipolar spindle assembly can ensue, leading to aneuploidy and increased risk for miscarriage/birth defects and cancer. In normal cells, what limits mother centrioles to assemble only a single daughter is unknown. It is known, however, that Polo-like kinase 4 (Plk4), the conserved master-initiator of centriole assembly, plays a key role in the duplication process. Therefore, a major goal of the Rogers lab is discovering how Plk4 works and how Plk4's activity is regulated.


II. Genomic Instability and Cancer

Genomic instability is a hallmark of cancer and promotes the formation of aggressive tumors. For some cancers, genome-wide alterations are not only common but occur early during cancer progression. Genomic instability can arise by multiple means. Notably, defects in centrosomes, the tiny organelles that facilitate cell division, are common in cancer, and cells with abnormal centrosome numbers experience mitotic errors that cause genomic instability. In addition, the extracellular environment of precancerous cells has a profound influence on various processes, such as maintaining cell polarity and the proper orientation of stem cell divisions -- errors in these processes can promote tumorigenesis and progression to metastasis. In collaboration with Dr. Anne Cress (UA Cancer Center), we are studying mechanisms that cause genomic instability using a model system developed in-house for that specific purpose (photo). Our goal is to identify specific molecular aberrations that drive genomic instability, and then exploit this knowledge to (1) develop therapeutic interventions that suppress genomic instability and (2) identify new markers that can be used to diagnose early stage cancer cells in patients.

Updated 5-16-2019