Page 24 - Hormel Institute Annual Report 2021-22

Rafael Contreras-Galindo, PhD
“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
24 | THE HORMEL INSTITUTE // Genome Instability and
Chromosome Biology
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’s disease.
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 are leveraging a highly specific and targeted rapid PCR methodol-
ogy to quantitatively assess the genomic landscape of centromeres in cancer cell lines and primary tissue. PCR-based profiling of centromeres revealed widespread heterogeneity of centromeric and pericentromeric sequences in cancer cells and tissues as compared to healthy counterparts. Quantitative reductions in centro- meric core and pericentromeric markers (α-sat- ellite units and HERV-K copies) were observed
in neoplastic samples as compared to healthy counterparts. Subsequent phylogenetic analysis of a pericentromeric 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
Cytogenetic analysis of SSc skin fibroblasts. Fibroblasts from skin biopsies of healthy individuals and SSc patients were arrested in metaphase with colchicine. Chromosomal spreads were stained with anti-CENPA (red) or anti-CENPB (green) antibodies. The nuclei/chromosomes were counterstained with DAPI. a) Healthy fibroblasts showing normal ploidy, b) Aneuploidy in dcSSc fibroblasts showing 52 chromosomes, c) Micronuclei in SSc fibroblasts (arrows), d) nuclear defects and micronuclei (arrows) in dcSSc and lcSSc.