A pinboard by
Hazheen Shirnekhi

I am a PhD Candidate at Colorado State University in Fort Collins, Colorado.


Uncovering the role of a newly identified mitotic protein, BuGZ, to understand its cancer lethality.

Our lab is interested in studying the process of cell division, mitosis, and how errors in this process can lead to genetic defects and cancers. Essential to mitosis is the attachment of each sister chromatid to spindle microtubules emanating from opposite spindle poles. The attachment occurs at the region of the chromatid known as a kinetochore, which is composed of around 100 proteins. The kinetochore is the focus of our lab’s work. We recently identified a new kinetochore protein that plays an important role during cell division, called BuGZ. We are interested in this protein because we find Glioblastoma cancer cells appear to require it for survival, while normal, healthy neural cells do not. To determine if BuGZ is truly a candidate for cancer therapies in the future, we must first ascertain what exactly it is doing during cell division. We currently know that it is important for the stability of a second protein, Bub3, which has known roles in the spindle assembly checkpoint. This checkpoint is critical for faithful segregation of the DNA, as it arrests cells in mitosis until all the proper attachments to the DNA are made, upon which the cell will be permitted to divide its DNA into two new cells and exit mitosis. We aim to determine if this link between BuGZ and Bub3 is at the root of its cancer lethality, or if BuGZ has additional Bub3-independent roles in mitosis. Our research is done in human cells and we use high resolution microscopy to definitively determine the phenotype in both cancer and healthy cells depleted of BuGZ. Preliminary data shows severe chromosome alignment defects in cancer cells depleted of BuGZ, while the healthy cells depleted of BuGZ do not show as severe defects. We are working to determine the cause of the alignment defects upon loss of BuGZ. Ultimately, we hope that the information gained from our research will contribute to the understanding of the fundamental characteristics of cancer cells and their ability to survive in condition that should lead to apoptosis.