Metabolic Regulation & Cell Function

Research focus

Metabolism is known to have a critical role in the regulation of cellular homeostasis and function. Much of this regulation is dependent on the fate of intracellular metabolites within a tightly interconnected network of reactions. In our lab, we use state-of-the-art technology of metabolic flux analysis to identify the mechanisms regulating the metabolic fate of intracellular metabolites and to understand how they impact cellular function. We primarily develop metabolically targeted approaches to improve the function of pancreatic beta-cells but we are also very much interested in applying this approach to models of stem cell differentiation, cancer and immunology.

Specific expertise

Pancreatic Beta-cells
Metabolic Flux Analysis and Regulation
Mass Spectrometry

Funding

Lab Members

Dr Alves, Tiago	Group leader	E-Mail
Mohanraj, Karthikeyan	PhD-student	E Mail
Laura Pedraza	PhD student	E-Mail

Selected Publications

Abulizi A, Cardone RL, Stark R, Lewandowski SL, Zhao X, Hillion J, Ma L, Sehgal R, Alves TC, Thomas C, Kung C, Wang B, Siebel S, Andrews ZB, Mason GF, Rinehart J, Merrins MJ, Kibbey RG. Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health. Cell Metab. Nov 3;32(5):751-766.e11 (2020)
Lewandowski SL, Cardone RL, Foster HR, Ho T, Potapenko E, Poudel C, VanDeusen HR, Sdao SM, Alves TC, Zhao X, Capozzi ME, de Souza AH, Jahan I, Thomas CJ, Nunemaker CS, Davis DB, Campbell JE, Kibbey RG, Merrins MJ.Pyruvate Kinase Controls Signal Strength in the Insulin Secretory Pathway. Cell Metab. Nov 3;32(5):736-750.e5 (2020)
Song JD, Alves TC, Befroy DE, Perry RJ, Mason GF, Zhang XM, Munk A, Zhang Y, Zhang D, Cline GW, Rothman DL, Petersen KF, Shulman GI. Dissociation of Muscle Insulin Resistance from Alterations in Mitochondrial Substrate Preference. Cell Metab. Nov 3;32(5):726-735e5 (2020).
Davis JC, Alves TC, Helman A, Chen JC, Kenty JH, Cardone RL, Liu DR, Kibbey RG, Melton DA. Glucose Response by Stem Cell-Derived β Cells In Vitro Is Inhibited by a Bottleneck in Glycolysis. Cell Rep. May 12;31(6):107623 (2020):
Jesinkey, S R, Madiraju, A K, Alves, T C, Yarborough, O H, Cardone, R L, Zhao, X, Parsaei, Y, Nasiri, A R, Butrico, G, Liu, X, Molina, A J, Rountree, A M, Neal, A S, Wolf, D M, Sterpka, J, Philbrick, W M, Sweet, I R, Shirihai, O H and Kibbey, R G. Mitochondrial GTP Links Nutrient Sensing to beta Cell Health, Mitochondrial Morphology, and Insulin Secretion Independent of OxPhos. Cell Rep28: 759-772 e10 (2019)
Yu, P, Wilhelm, K, Dubrac, A, Tung, J K, Alves, T C, Fang, J S, Xie, Y, Zhu, J, Chen, Z, De Smet, F, Zhang, J, Jin, S W, Sun, L, Sun, H, Kibbey, R G, Hirschi, K K, Hay, N, Carmeliet, P, Chittenden, T W, Eichmann, A, Potente, M and Simons, M. FGF-dependent metabolic control of vascular development. Nature545: 224-228 (2017)
Madiraju, A K, Alves, T, Zhao, X, Cline, G W, Zhang, D, Bhanot, S, Samuel, V T, Kibbey, R G and Shulman, G I. Argininosuccinate synthetase regulates hepatic AMPK linking protein catabolism and ureagenesis to hepatic lipid metabolism. Proc Natl Acad Sci U S A113: E3423-30 (2016)
Alves, T C, Pongratz, R L, Zhao, X, Yarborough, O, Sereda, S, Shirihai, O, Cline, G W, Mason, G and Kibbey, R G. Integrated, Step-Wise, Mass-Isotopomeric Flux Analysis of the TCA Cycle. Cell Metab22: 936-47 (2015)
Alves, T C, Befroy, D E, Kibbey, R G, Kahn, M, Codella, R, Carvalho, R A, Falk Petersen, K and Shulman, G I. Regulation of hepatic fat and glucose oxidation in rats with lipid-induced hepatic insulin resistance. Hepatology53: 1175-81 (2011)