Page 26 - Hormel Report 2021

Rafael Contreras-Galindo, Ph.D.
“Changes in the structure and function of centromeres lead to chromosome instability and rupture of nuclear integrity, which are hallmarks of fibrosis and cancer.
I am exploring the contribution of these changes to disease and exploring therapies to interfere these
processes.”
Rafael Contreras-Galindo
26 | THE HORMEL INSTITUTE // Genome Instability and
Chromosome Biology
SECTION LEADER / ASSISTANT PROFESSOR
UNIVERSITY OF MINNESOTA
My research interests are focused on investigating the function of repetitive areas of the human genome. I have a
special interest in centromere genomics. The centromere is the structural unit responsible
for the correct segregation of chromosomes during cell division. Destabilization of centromere function results in chromosomal mis-segregation and instability, hallmarks of fibrosis, cancers and birth defects. I am investigating the structure and evolution of centromere sequences, the epigenetic interactions of chromatin factors that modulate centromere function on centromere sequences, and the role these elements play in chromosome segregation and genome instability in non-disjunction disorders, cancers, fibrosis, and Alzheimer.
Centromeres in cancer
Centromere genomics remain poorly character- ized in cancer, due to technologic limitations in sequencing and bioinformatics methodologies that make high-resolution delineation of centro- meric loci difficult to achieve. We here leverage
a highly specific and targeted rapid PCR method- ology to quantitatively assess the genomic land- scape of centromeres in cancer cell lines and pri- mary tissue. PCR-based profiling of centromeres revealed widespread heterogeneity of centromer- ic and pericentromeric sequences in cancer cells and tissues as compared to healthy counterparts. Quantitative reductions in centromeric core and pericentromeric markers (α-satellite units and HERV-K copies) were observed in neoplastic samples as compared to healthy counterparts. Subsequent phylogenetic analysis of a pericen- tromeric endogenous retrovirus amplified by
PCR revealed possible gene conversion events occurring at numerous pericentromeric loci in the setting of malignancy. Our findings collectively represent a more comprehensive evaluation of centromere genetics in the setting of malignancy, providing valuable insight into the evolution and reshuffling of centromeric sequences in cancer development and progression. Currently, we are