Our goal is to understand how obesity increases the risk of liver cancer by investigating the mechanisms through which excess nutrients lead to fatty liver and subsequently to liver cancer. Obesity, driven by excessive food intake, is a significant health issue in Texas, where it dramatically impacts HCC rates. Despite the known link between obesity and liver cancer, the precise mechanisms remain poorly understood due to the lack of appropriate models. To address this, we developed an obesity-induced liver cancer mouse model. Preliminary data from our advanced imaging techniques revealed a critical two-step process in organelle contact formation during the transition from fatty liver to canc...

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Our goal is to understand how obesity increases the risk of liver cancer by investigating the mechanisms through which excess nutrients lead to fatty liver and subsequently to liver cancer. Obesity, driven by excessive food intake, is a significant health issue in Texas, where it dramatically impacts HCC rates. Despite the known link between obesity and liver cancer, the precise mechanisms remain poorly understood due to the lack of appropriate models. To address this, we developed an obesity-induced liver cancer mouse model. Preliminary data from our advanced imaging techniques revealed a critical two-step process in organelle contact formation during the transition from fatty liver to cancer: 1) mitochondrial fragmentation and 2) the formation of mitochondria-rough endoplasmic reticulum (ER) contact through the mitochondria-associated ER membrane (MAM). We hypothesize that this mitochondria-ribosome-ER contact is essential for maintaining energy and protein homeostasis, promoting ER enlargement/stress, inflammation, and ultimately, cancer development. To test this hypothesis, we will determine the significance of mitochondrial fragmentation and MAM formation in obesity-induced HCC, investigate the molecular mechanisms underlying ER stress and ribosome accumulation, and examine the impact of mitochondria-ribosome-ER contact in human obesity-associated HCC. By elucidating the dynamic changes and physiological roles of organelle communication, our research aims to shed new light on the pathogenic mechanisms linking obesity to liver cancer development. This understanding could lead to novel strategies for early detection, prevention, and treatment of liver cancer, ultimately reducing the burden of obesity-associated cancer and improving patient outcomes. Our findings will be particularly significant in regions like South Texas, where liver cancer incidence among obese individuals is notably high, and could provide a foundation for targeted therapeutic interventions.

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