Meet The Researcher: Sarah DiDomenico Expects That More Therapeutics Will Use Synthetic Lethality
Sarah DiDomenico always gravitated toward science in school, but she credits her eighth-grade science teacher for really igniting her passion.
“She often taught off-textbook, engaging us in many hands-on projects, and showed me the joy in learning and discovery,” she said.
Sarah explains that her teacher invited her class to enter in the science fair, which was the first time she had to independently identify a need, develop hypothesis-driven question and follow the scientific method to reach a conclusion.
“That experience set me on the path to pursue research as a career,” she said. “The potential to one day help people by researching human disease and developing therapeutics was very exciting to me.”
In high school, she became interested in studying genetics after learning about mitosis and meiosis in biology class. It was this interest that eventually lead her to apply to colleges with genomics or molecular biology degrees.
DiDomenico attended Gettysburg College in Pennsylvania for her undergraduate degree where she majored in Biochemistry and Molecular Biology and participated in undergraduate research. While completing her major, she participated in research focusing on DNA repair pathways in bacteria. In addition to this, she took a molecular genetics course in her junior year, where she was introduced to all of the different types of DNA damage and the many pathways that are responsible for repair.
“I loved learning about the intricacies of these repair mechanism, and knew then that I wanted to study human disease through this lens in graduate school,” she said.
She applied to PhD programs with faculty in the DNA repair field, because she was hoping to pursue this area of research. She was accepted into a program at a different university and joined Dr. Alexander Mazin’s lab for her thesis project. However, when Dr. Mazin was offered a faculty position here at UT Health San Antonio, he invited her to apply to UT Health San Antonio and continue her thesis work here with him.
“I am very passionate about my project and enjoy working in the Mazin lab, and wanted the opportunity to continue. Once I started researching UT Health San Antonio, it made the decision to apply to the IBMS program very easy,” she said. “There are many premier DNA repair labs here, which is an amazing opportunity for collaboration and to learn from experts in the field.”
As a student in the Biochemical Mechanisms in Medicine discipline of the Integrated Biomedical Sciences Ph.D. program, she is able to do basic science research, while also contributing to the development of a potential cancer therapeutic.
Her research is focused on the development and characterization of small molecule inhibitors to selectively kill BRCA deficient cancer cells.
“Breast and ovarian cancers often have mutations in the BRCA genes, which are important for repairing broken or damaged DNA. Mutations can cause these genes to be non-functional, and the cancer cell must rely on other repair pathways to fix DNA breaks. A protein called RAD52 is involved in the backup mechanism. Interestingly, inactivating RAD52 in a normal cell does not cause cell death, but when RAD52 is inactivated in cells with mutations in the BRCA genes, it kills these cells.”
She explained that this phenomenon is called synthetic lethality, and is very attractive from a therapeutic standpoint.
“If we can target and inactivate RAD52 with a small molecule inhibitor,” she said. “We can potentially kill BRCA deficient cancer cells while leaving healthy, non-cancerous cells unharmed. There are already therapeutics on the market that have used synthetic lethality as a basis for their development, and I think the number will only increase.”
One of the main aspects that she enjoys at UT Health San Antonio is the willingness of students and faculty to collaborate.
“I really appreciate how kind the students and faculty are. The faculty are open to forming collaborations and teaching new techniques. They also offer advice and new perspectives on your project.”
After graduate school, she is interested in applying for postdoctoral positions in industry, particularly in Research and Development where she can identify therapeutic targets for drug development. But, she’s not set on one career path and still exploring the different options available to PhDs.
Outside of graduate school, she enjoys being active and outdoors; practicing yoga, hiking and running. She also loves to spend time at home with her two pet bunnies.
This article was written by Charlotte Anthony, marketing specialist at the Graduate School of Biomedical Sciences at UT Health San Antonio. This article is part of the “Meet The Researcher” series which showcases researchers at the Graduate School of Biomedical Sciences at University of Texas Health Science Center San Antonio.