UTHSC-led researchers receive $5.2 million to study obesity-mediated cancer risk

The National Cancer Institute has awarded more than $5.2 million to a team led by researchers at the University of Tennessee Health Science Center (UTHSC) for a study that will address critical gaps in knowledge about obesity-related cancer risk will close. Liza Makowski, PhD, professor in the Department of Hematology and Oncology at UTHSC College of Medicine, is the award’s lead investigator.

Obesity has been linked to an increased risk and poorer prognosis for various types of cancer. A number of related factors contribute to the tumor-promoting effects of obesity, including suppression of the immune system (immunosuppression). The underlying mechanisms that control how and to what extent obesity-mediated immunosuppression increases cancer risk remain an untapped niche in cancer research.

The team of dr. Makowski hypothesizes that obesity alters the gut microbiome, which may impact the immune system’s ability to monitor cancer onset, possibly through microbially-derived metabolites. In this project, the team will study patients undergoing bariatric surgery to track metabolic and immune changes associated with weight loss over time. In a complementary study, healthy subjects who are slim or obese, of different ages and races will be examined for certain biomarkers of risk. Advanced single-cell sequencing and informatics will help define associations that identify at-risk patients using machine learning. Preclinical studies are being conducted to identify the specific cellular machinery in precancerous microenvironments that have a major impact on cancer onset and progression. They will test these mechanisms to determine how microbially modified metabolites can affect the interaction between immune and cancer cells.

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This award connects investigators from four other universities working with UTHSC. The other two principal researchers 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 key collaborators on this project.

We are pleased to be one of five projects selected by NCI to study obesity and cancer risk as part of 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 cancer patient outcomes, offering our extraordinary transdisciplinary team the opportunity to leverage impactful lifestyle changes or develop therapeutic strategies for cancer risk reduction interventions. The results of this study will define useful mediators of obesity-related cancer risk that will shed light on how to reduce cancer risk or improve treatments.”

Dr. Liza Makowski, PhD, Professor in the Department 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 Computer Science.

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