Beth Osia, University of Iowa Integrated Biology doctoral alumnus and winner of the 2022 Rex Montgomery Dissertation Prize Award, has already created a big impact both at the collegiate level and in the field of cancer research itself. However, before finding her groove as a professional scientist, Osia says she struggled with the overall process.

“Before I attended grad school, I felt like I could perform tasks as a technician, but I didn’t know what it meant to take on a scientific project and be completely responsible for it,” Osia says. “My initial lack of confidence put me in a lot of discomfort, but that’s where I grew the most. My time as a graduate student improved my ability to investigate and drive my research forward.”

Not only did Osia come into her own, but she also demonstrated that she has what it takes to excel in her chosen field. During her time at Iowa, Osia co-authored to ten published research papers, presented her results at multiple international scientific conferences, and contributed to several successful National Institutes of Health (NIH) grants. In July 2022, Osia won the Rex Montgomery Dissertation Prize Award which recognizes the most commendable dissertation by a doctoral student conducting research in the prevention of disease.

“I am extremely honored to have received this dissertation award,” Osia says. “It's wonderful to see my research and field recognized in such a way, and really speaks to the excellent training I received from my department and mentors. Additionally, graduating in 2020 meant that I was not able to attend an in-person graduation ceremony, so winning this award also provided me with a little extra closure to my time as a graduate student at Iowa.”

Osia’s academic journey began when she joined Dr. Anna Malkova’s research lab in 2014 to help further the understanding of how DNA molecules are maintained and repaired when broken.

Osia studied two pathways used by cells to repair broken DNA molecules and the broader effects of such repair. Specifically, she studied break-induced replication (BIR) and microhomology-mediated BIR (MMBIR). These two unusual repair processes involve copying and pasting DNA rather than connecting the broken DNA strands back together. BIR and MMBIR pathways are known to cause DNA mutations and Osia set out to confirm if these repair pathways specifically promote mutations in human cancers.

Osia first studied the BIR pathway using baker’s yeast, which is commonly used in the study of genetics. According to Osia, yeast is beneficial to use because it “shares a variety of homologous genes with human cells and is easy to manipulate.” The genetic experiments she performed in yeast led Osia to discover how DNA mutations caused by BIR can arise in cancerous cells.

“Certain patterns of mutations caused by the enzymes that participate in BIR had been observed in cancer but were never fully explained by our understanding of the BIR mechanism,” she explains. “Because of my research, we now have a better understanding of how BIR produces these mutations that may promote cancer in humans, which is an exciting advance.”

The next phase of her academic studies aimed to establish a mutation pattern for the second repair pathway, MMBIR, which is a DNA repair process associated with cancer and congenital diseases. To do so, Osia analyzed MMBIR mutations in whole genome sequencing from a public database and compared normal, healthy tissue with cancerous tumors. In collaboration with University of Iowa Computer Science alumnus, Dr. Thamer Alsulaiman, Osia built the software, MMBSearch, to investigate these sequenced human genomes.

“The software compares tumors and normal tissue samples to analyze whether there is an accumulation of MMBIR mutations specifically in the tumor cells,” Osia says. “We found that the majority of the different types of cancer we surveyed had increased levels of MMBIR mutations, which confirms the cancer relevance of MMBIR.”

Not only was MMBSearch successful in confirming the role MMBIR plays in cancer cells, but the software has also continued to be used since Osia’s completed doctoral degree in 2020. Other students in the Malkova lab are now using MMBSearch in their own research, and Osia is thrilled that they are able to use the tool she created to benefit their ongoing studies. The software Osia developed has also created an impact on a larger scale in the field of cancer therapeutics.

“The MMBIR mutations that we found in the genomes of cancer cells are not found very often in normal cells, meaning they are cancer-specific,” Osia says. “As people begin to understand the MMBIR pathway better, we can start to target it to create better cancer therapeutics.”

Osia’s outstanding work has helped the cancer therapeutics field take one step closer to targeting DNA repair pathways. In her recommendation letter for the Rex Montgomery Dissertation Prize Award, Malkova describes Osia as a “top class geneticist who has made seminal contributions to the field of cancer and genomic instability promoting cancer.” Osia continues to make strides in this field in her postdoctoral work at City of Hope, a top cancer treatment and research center in Los Angeles, California, where she researches DNA repair proteins to improve cancer treatment.