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Metabolic rewiring during fibrosis

Accumulation of fat in the liver as seen in non-alcoholic fatty liver disease (NAFLD) can cause fibrosis and inflammation that impede liver function. We aim understand how metabolism of the cells that cause fibrosis changes during disease progression.  To achieve this goal, we are developing in vivo isotope tracing techniques to study cell-type specific metabolism.  

Zhang, Z.*, TeSlaa, T.*, Xu, X., Zeng, X., Yang, L., Xing, G., Tesz, G.J., Clasquin, M.F., & Rabinowitz, J. D. (2021). Serine catabolism generates liver NADPH and supports hepatic lipogenesis. Nature metabolism, 3(12), 1608-1620. [link][PDF]

Metabolism can drive changes in cellular identity. This concept has been mostly studied in proliferative cell types such as cancer and stem cells, but it is less clear the role that metabolism plays more terminally differentiated cell types.  We are interested in how metabolism alters cellular function in adult tissues and drives processes like fiber type switching in the muscle or activation of fibroblasts during development of fibrotic diseases.

 TeSlaa, T., Chaikovsky, A. C., Lipchina, I., Escobar, S. L., Hochedlinger, K., Huang, J., Graeber, T.G., Braas, D., & Teitell, M. A. (2016). α-Ketoglutarate accelerates the initial differentiation of primed human pluripotent stem cells. Cell metabolism, 24(3), 485-493. [link][PDF]

How metabolism influences cellular fate and function

Muscle fiber type specific metabolism 

Different types of muscle fibers have their own unique metabolism. We found that red muscle, despite being classically known for being oxidative and fat burning, has very active glycolytic metabolism. Our future interests include:

  • understanding the mechanisms that control differences in glucose metabolism in red and white muscle

  • exploring the role of red muscle in the development of type II diabetes

  • manipulation of red muscle to improve whole-body metabolic health 

TeSlaa, T., Bartman, C. R., Jankowski, C. S., Zhang, Z., Xu, X., Xing, X., Wang, L., Lu, W., Hui, S., & Rabinowitz, J. D. (2021). The source of glycolytic intermediates in mammalian tissues. Cell metabolism, 33(2), 367-378. [link][PDF] 

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