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UTHSC Researchers Collaborate on $2 Million Grant To Study Immune System and Triple Negative Breast Cancer

Dr. Liza Makowski

Liza Makowski, PhD, a professor in the Department of Medicine-Hematology-Oncology at the University of Tennessee Health Science Center, and Joseph F. Pierre, PhD, an assistant professor in the Department of Pediatrics-Obesity at UTHSC, have received $2.1 million from the National Cancer Institute for a five-year study to examine how the microbiome impacts the immune system and response to immunotherapy for an aggressive type of breast cancer called triple negative breast cancer.

Drs. Makowski and Pierre met in 2017 in the Metabolism Research Interest Group seminar series that meets the first Friday of every month at UTHSC. They share expertise in obesity and metabolism and realized their complementary interests would serve them well in their pursuits to understand mechanisms that regulate the innate immune response in diseases exacerbated by obesity.

“After a few meetings, it made sense to pool our skill sets to try to understand how to better impact breast cancer outcomes,” Dr. Makowski said. “In this case, it was like the grant almost wrote itself once Joe and I generated some solid preliminary data together. We are very excited to be able to pursue this project with this R01 funding.” Their project is titled “Role of microbial-modulated bile acid receptor signaling in breast cancer.”

Combining Dr. Makowski’s experience in reprogramming the tumor microenvironment in obesity-associated triple negative breast cancer with Dr. Pierre’s focus on microbial regulation of metabolites in obesity-associated metabolic dysfunction was a natural and easy collaboration. “Sometimes you meet someone with complementary expertise that opens your eyes to pathways or diseases you never thought you would study,” he said. “Liza had never studied the microbiome and I have never studied breast cancer. Therefore, this is truly a synergistic project.”

Microbes from the gut or extra-intestinal sites across the body can influence immunosurveillance, which keeps tumors at bay, as well as chemotherapy and immunotherapy efficacy, which shapes cancer outcomes and survival. However, much needs to be studied to understand how microbes impact cancer outcomes.

Breast cancer is the most-common cancer and the second-leading cause of death in women in the United States. Triple negative breast cancer is an aggressive subtype that disproportionately affects the young and minorities, such as Black and Latina women. Memphis is the ideal location to conduct studies on such cancers that are associated with health disparities, in order to expand research to best serve and support the community. This type of breast cancer has generally eluded personalized medicine approaches, leaving only chemotherapy with few recent advances. Findings from the work of Drs. Makowski and Pierre could have future impact on clinical studies to improve patient care.

Dr. Joseph Pierre

Dr. Makowski is a member of the UTHSC Center for Cancer Research. She received her PhD at Harvard Chan School of Public Health and completed a postdoctoral fellowship in the Stedman Center for Nutrition and Metabolism at Duke University Medical Center. She was named an associate professor with tenure in the Department of Nutrition in the Division of Biochemistry at Gillings School of Global Public Health at the University of North Carolina at Chapel Hill. She moved to UTHSC in 2017. Dr. Pierre, the director of UTHSC Gnotobiotics, received his PhD at the University of Wisconsin-Madison and completed his postdoctoral studies at the University of Chicago at the Knapp Center for Biomedical Discovery. He started his first faculty position at UTHSC in 2017.

Other UTHSC faculty who serve as co-investigators on the award include Matthew Davis, MD, assistant professor in the Department of Surgery; Ramesh Narayanan, PhD, professor in the Department of Medicine-Hematology and Oncology;  Elizabeth “Liz” Fitzpatrick, PhD, associate professor in the Department of Microbiology, Immunology and Biochemistry; Athena Starlard-Davenport, PhD, assistant professor in the Department of Genetics, Genomics, and Informatics, and Michelle Puchowicz, PhD, associate professor in the Department of Pediatrics. Drs. Makowski and Pierre will also collaborate with Katherine Cook, PhD, at Wake Forest University on this study.