Thomas Kizzar

Current Research

Functional exploration of lysosomal lipid regulators in metabolic disease. 

In mammalian organisms, the liver is a central organ that is crucial for energy homeostasis through glucose and lipid metabolism for energy expenditure and body temperature regulation. At the cellular level, hepatocytes (liver cells) contain organelles called lysosomes that break down stored energy molecules and damaged organelles to serve as a nutrient sensor. When this process is disrupted by mutations in lysosomal genes or environmental stressors like fasting, metabolic diseases can occur. These functions require Bis(monoacylglycero)phosphate (BMP) lipids, negatively charged membrane lipids that form vesicles in the lysosome to sequester degradative enzymes. BMP lipid levels have been found to be significantly elevated in a multitude of metabolic stresses and disease such as: cold exposure, lysosomal storage diseases, cardiovascular disease, and neurodegeneration. Interestingly, these increases are exacerbated in diverse populations with higher prevalence of metabolic disease and dyslipidemia, such as United States Native populations. Despite their critical role in lysosomes, the regulation and metabolism of BMP lipids are poorly characterized. My project focuses on identifying BMP lipid regulators would inform on metabolic disease progression and mechanisms allowing for the exploration of therapeutic targets that are relevant to diverse populations, including Native Americans with metabolic disease.