Research

Metabolic rewiring during steatotic liver disease

Accumulation of fat in the liver as seen in metabolism associated steatotic liver disease (MASLD) can cause fibrosis and inflammation that impede liver function. We aim understand the role that different nutrients play in supporting healthy liver function and how poor diet influences liver disease. Currently we are using in vivo stable isotope tracing to better understand how nutrients are used in the liver and how their use is altered with poor diet or in steatotic disease. We also aim to understand the metabolism of the cells that cause fibrosis, hepatic stellate cells. 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]