Identifying genomic instability seen in FA cells: Nichole Owen, PhD candidate

Nichole Owen

Student makes important contribution to Bloom Syndrome cancer research

ARCS scholar Nichole Owen, a graduate student in the Susan Olson Lab, is working to help unravel the mystery of a rare blood disorder passed from parents to their children—a disease that ultimately strikes many young people in the prime of their lives.

Her research is focused on a disease called Fanconi anemia, or FA, an inherited blood disorder which prevents bone marrow from making enough new blood cells for the body to work normally. First described in 1927 by Swiss pediatrician Guido Fanconi, FA can cause bone marrow to make faulty blood cells, leading to serious health problems, such as bone marrow failure, leukemia and cancer. The average life expectancy of a patient with FA is 24 years.

"One of the hallmarks of Fanconi anemia is the presence of abnormal chromosome associations, or radial formations, visible through the light microscope," said Nichole. "The presence of these structures, when combined with the clinical features of the syndrome, is diagnostic of the disorder."

Previous work in the Olson Lab demonstrated that these abnormal radial formations form primarily between non-homologous chromosomes. Though the cause of radial formation is poorly understood, it's thought to involve aberrant DNA repair. Because radials are thought to contribute significantly to the genomic instability seen in FA cells, Nichole's research attempts to identify the proteins responsible for the formations.

"Nichole arrived in my lab with a very valuable skill set," said Susan Olson, PhD, Professor, Department of Molecular & Medical Genetics. "This included chromosome preparation and immunohistochemistry techniques, which allows her the unique opportunity to observe specific proteins involved in these formations."

By investigating the instability of FA chromosomes, Nichole is not only contributing to a better understanding of the disorder, but her work has impacted other areas of science, particularly in the field of cancer.

"Nichole has shown that this phenomenon of non-homologous association extends to other syndromes of faulty DNA damage repair," said Dr. Olson. "Specifically, she has provided solid evidence to resolve a long-standing dispute in the field of genomic instability regarding whether radial formations in Bloom syndrome patients occur between homologous versus non-homologous chromosomes."

While her science focuses on the DNA repair defect and unstable chromosome aspects of FA, Nichole says this has made her appreciate the cancer aspect even more, especially how it relates to people her age. "Fanconi anemia patients are likely to develop a range of cancers and at a much younger age than patients in the general population," she said. "Making their prognosis more difficult is the fact that they can't undergo certain parts of cancer therapy because radiation and chemotherapeutic agents do more harm than good, exacerbating the genome instability problems they already inherently have."

"We are making progress on diseases like Fanconi anemia and Bloom syndrome," said Dr. Olson. "Every day we make important discoveries that push us one step closer toward finding a cure. Nichole and her generation of scientists are the ones who will finish this work."

Nichole has presented her findings at graduate studies retreats and at the recent Rare Disease Day conference at OHSU. Read more about the conference on SoM Research Voice (OHSU login required).

Pictured: Dr. Olson (left) and Nichole Owen