The National Cancer Institute has awarded more than $5.2 million to a team lead by researchers from the University of Tennessee Health Science Center (UTHSC) for a study that will fill critical gaps in knowledge around obesity-mediated cancer risk. Liza Makowski, PhD, professor in the Division of Hematology and Oncology in the UTHSC College of Medicine, is the lead investigator on the award.

Obesity has been linked to an increased risk of and a worse prognosis for several types of cancer. A number of related factors contribute to obesity's pro-tumor effects, including suppression of the immune system (immunosuppression). The underlying mechanics that control how and to what extent obesity-mediated immunosuppression increases cancer risk remains an untapped niche in cancer research.

Dr. Makowski's team hypothesizes that obesity changes the gut microbiome, which can impact the immune system's ability to keep watch on the start of cancer, potentially through microbially-derived metabolites. In this project, the team will study patients undergoing bariatric surgery to follow metabolic and immune changes with weight loss over time. In a complementary study, healthy subjects who are lean or obese of varying age and races will be examined for certain biomarkers of risk. Advanced single cell sequencing and informatics will help define associations identifying patients at risk using machine learning. Pre-clinical studies will be conducted to identify the specific cell machinery in pre-cancerous microenvironments that have high impact on the start and progression of cancer. They will test these mechanisms to determine how microbially-modified metabolites may impact immune-cancer cell crosstalk.

This award bridges investigators across four additional universities working with UTHSC. The two other principal investigators are Joseph Pierre, PhD, assistant professor in the College of Agriculture and Life Science at the University of Wisconsin-Madison, and Jeffrey Rathmell, PhD, director of the Vanderbilt Center for Immunobiology and associate director of the Vanderbilt Institute of Infection, Immunology, and Inflammation. Colleagues from Wake Forest University School of Medicine and the University of Memphis College of Health Sciences are also integral collaborators on this project.

We are excited to be one of five projects chosen by the NCI to examine obesity and cancer risk as part of the NCI's Metabolic Dysregulation and Cancer Risk Program. The Mid-South has a diverse population with a large minority representation, high rates of obesity, and tragically poor patient cancer outcomes, which pose an opportunity for our exceptional transdisciplinary team to leverage impactful lifestyle changes or generate therapeutic strategies for interventions to decrease cancer risk. Outcomes from this study will define beneficial mediators of obesity-mediated cancer risk that will shed light on how to reduce the risk of cancer or improve treatments."

Dr.Liza Makowski, PhD, Professor in the Division of Hematology and Oncology, UTHSC College of Medicine

Other UTHSC investigators on the team include bariatric surgeon Matthew Davis, MD, in the Department of Surgery; Francesco Giorgianni, PhD, in the Department of Pharmaceutical Sciences; and Robert Williams, PhD, Lu Lu, MD, and David Ashbrook, PhD, in the Department of Genetics, Genomics, and Informatics.