Page 24 - Hormel Report 2023

Rafael Contreras-Galindo, PhD
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 chro- mosomes, c) Micronuclei in SSc fibroblasts (arrows), d) nuclear defects and micronuclei (arrows) in dcSSc and lcSSc.
“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 func- tion 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 and fibrosis.
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 meth-
odology to quantitatively assess the genomic landscape of centromeres in cancer cell lines and primary tissue. Currently, we are recreating these mutations occurring in cancer cells in chromo- somally normal human cells using CRISPR Cas9 to determine the effect of centromere instability on centromere assembly and function and chromosome segregation. These studies will help us to understand the role of centromere deletion in genome instability and aneuploidy seen in cancer. In addition, we study the function of centromeric proteins in cancer.