A University of Tennessee Health Science Center team has received $2.05 million from the National Cancer Institute for an advanced genetics project that could help develop targeted therapies and personalized treatment for breast cancer. Liza Makowski, PhD, professor of Hematology and Oncology in the College of Medicine, is the lead investigator on the award.
Developing new therapies for breast cancer depends on a deeper understanding of individual genetics. Pre-clinical research is often hampered by the lack of genetic diversity in most animal models, which does not represent the wide variation in humans. Dr. Makowski’s team has created a pre-clinical model using one of the largest and best genetic reference populations, the BXD family of mice. The team crossed the BXD with a model that develops triple negative breast cancer, creating unique hybrids with robust, reliable, and reproducible phenotypic and genomic variation. The genetic variation will be analyzed to determine which regions of DNA contribute to certain characteristics of the breast cancer.
Dr. Makowski’s preliminary data show large differences in triple-negative-breast-cancer characteristics, including early onset tumors, which suggests genetic modifiers impact disease. The team will also test therapies to pinpoint underlying genetics, which will help identify genetic strains that respond well to therapy.
The goal is to identify and validate underlying genetic modifiers of breast cancer, enabling advances to improve predictive and personalized treatments.
“This model allows researchers to test the underlying genetics on the impacts of cancer timing, severity, and response to different therapies to identify candidate genes using advanced systems genetics,” Dr. Makowski said.
Dr. Makowski’s interdisciplinary team has extensive expertise in chemo- and immune therapy in pre-clinical breast cancer models, immunology, pathology, systems genetics, and advanced computational methods. From UTHSC’s department of Genetics, Genomics and Informatics are Rob Williams, PhD, department chair and professor, Lu Lu, MD, professor, and David Ashbrook, PhD, assistant professor. Neil Hayes, MD, MPH, director of the UTHSC Center for Cancer Research, is also on the team.
