Research

Dr. Liza Makowski’s lab studies how immune cells under states of metabolic stress alter the progression of diseases including obesity and cancer. Her lab‘s primary interest is in how macrophage function could be altered by manipulating fuel availability and metabolism.  Her lab uses cell culture studies, biochemical assays, preclinical models, and genomic/metabolomic profiling to address questions of interest. Ultimately, the goal of our work is to identify pathways or proteins that may be used to manipulate metabolism in order to improve the inflammatory and metabolic status of individuals. To date, the Makowski lab has demonstrated that altering fuel substrates at the systemic or cellular level can modulate the inflammatory response in obese adipose (white and brown) and liver, as well as in normal breast and murine carcinoma models. To undertake these studies, Makowski holds a ROO Pathway to Independence Award entitled Macrophage Mitochondrial Stress in Inflammation, Insulin Resistance & Obesity to examine the complex links between fuel metabolism and inflammation. Her research is also supported by a U01 Pregnancy, Obesogenic Environment, and Basal-like Breast Cancer awarded in 2010.  This project is dissecting the role of parity and post-partum diet-induced weight gain on the development of basal-like breast carcinoma. In addition, the Dr. Makowski received two pilot and feasibility grants through UNC NORC and CGIBD grants to examine the role of glucose metabolism in inflammation in adipose and the liver.

Current Projects:

Cafeteria Diet and Obesity-induced Inflammation: To examine the role of obesity-induced inflammation, we showed that the Cafeteria Diet, a human junk food diet that drives a phenotype of dramatic rapid onset obesity with glucose intolerance, drove severe inflammation in liver, brown and white adipose. It proved to be a more robust model of human Metabolic Syndrome compared to traditional lard-based high fat diet used in most rodent studies. Through genomic and metabolomic profiling, we have identified defects in anti-oxidant defense as well as novel lipid metabolites as biomarkers of insulin resistant and adipose inflammation, which we demonstrated mediate activation of pro-inflammatory pathways.

Macrophage Mitochondrial Stress in Inflammation, Insulin Resistance & Obesity: To study altered lipid delivery, we are investigating the role of two fuel transporters. FATP1, which transports fatty acids into the cell, is under investigation using over-expression in macrophage cell lines and knockout mouse model diet-induced obesity studies. We are also examining the role of glucose transporter GLUT1 and glucose metabolism in inflammation in adipose and the liver, using over-expression in macrophage cell lines and knockout mouse model diet-induced obesity studies .

Pregnancy, Obesogenic Environment, and Basal-like Breast Cancer: Another ongoing project examines the role of the macrophage in post-partum high fat diet-induced weight gain and the development of basal-like breast carcinoma. UNC Breast Cancer and the Environment Research Program link.

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