The regulation of growth and metabolism
Insulin, growth, Akt/PKB, diabetes, drosophila, metabolism, glucose transport, membrane protein trafficking, signal transduction.
Description of Research
The ability to respond to nutritional stress is one of the most primitive adaptations that organism must accomplish. The pathways that alert the organism to an absence of food and initiate an appropriate response are remarkably well-conserved and involve such critical signaling molecules as the protein kinases Akt and AMP-activated protein kinase (AMPK) as well as nutrient sensors such as the carbohydrate response element binding protein (ChREBP).
The Birnbaum lab studies this complex biological response in two contexts: the initiation of cell growth after a transition from nutritional deprivation to abundance and the insulin-dependent redistribution of simple substrates into long-term energy stores. The latter process involves a number of distinct but interacting components such as glucose-stimulated insulin secretion, and the insulin-dependent acceleration of hepatic lipid synthesis and glucose uptake into adipocytes and muscle. Two aspects of the regulation of glucose transport by insulin, both of which are studied in the Birnbaum lab, are the way in which insulin regulates the movement of hormone-sensitive Glut4 glucose transporter from the inside of the cell to the plasma membrane, and the signaling pathway by which insulin accomplishes this. There are also a number of projects underway aimed at understanding how the evolutionarily conserved sensor of nutritional stress, AMP-activated protein kinase, regulates carbohydrate and fat metabolism. These fundamental biological problems are addressed using experiments performed in tissue culture cells, mice and the genetically tractable organism Drosophila melanogaster.
Please contact Dr. Birnbaum for projects.
Michelle Bland, Postdoctoral Fellow,
Abby Dean, Postdoctoral Fellow,
Sarah Choi, Graduate student,
Danielle Gross, Postdoctoral Fellow,
Karla Leavens, Graduate Student,
Mingjian Lu, Postdoctoral Fellow,
Russell Miller, Postdoctoral Fellow,
David Tucker, Postdoctoral Fellow,
Min Wan, Postdoctoral Fellow,
Bob Monks, Research Assistant,
Qingwei Chu, Research Assistant,
Maureen Victoria, Research Assistant,
Cass Lutz, Administrator
Rastogi Ruchi, Jiang Zhongliang, Ahmad Nisar, Rosati Rita, Liu Yusen, Beuret Laurent, Monks Robert, Charron Jean, Birnbaum Morris J, Samavati Lobelia: Rapamycin Induces Mitogen-activated Protein (MAP) Kinase Phosphatase-1 (MKP-1) Expression through Activation of Protein Kinase B and Mitogen-activated Protein Kinase Kinase Pathways. The Journal of biological chemistry 288(47): 33966-77, Nov 2013.
Wan Min, Leavens Karla F, Hunter Roger W, Koren Shlomit, von Wilamowitz-Moellendorff Alexander, Lu Mingjian, Satapati Santhosh, Chu Qingwei, Sakamoto Kei, Burgess Shawn C, Birnbaum Morris J: A noncanonical, GSK3-independent pathway controls postprandial hepatic glycogen deposition. Cell metabolism 18(1): 99-105, Jul 2013.
Kim Jiyeon S, Sklarz Tammarah, Banks Lauren B, Gohil Mercy, Waickman Adam T, Skuli Nicolas, Krock Bryan L, Luo Chong T, Hu Weihong, Pollizzi Kristin N, Li Ming O, Rathmell Jeffrey C, Birnbaum Morris J, Powell Jonathan D, Jordan Martha S, Koretzky Gary A: Natural and inducible TH17 cells are regulated differently by Akt and mTOR pathways. Nature immunology 14(6): 611-8, Jun 2013.
Miller Russell A, Chu Qingwei, Xie Jianxin, Foretz Marc, Viollet Benoit, Birnbaum Morris J: Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP. Nature 494(7436): 256-60, Feb 2013.
Newman Robert H, Hu Jianfei, Rho Hee-Sool, Xie Zhi, Woodard Crystal, Neiswinger John, Cooper Christopher, Shirley Matthew, Clark Hillary M, Hu Shaohui, Hwang Woochang, Jeong Jun Seop, Wu George, Lin Jimmy, Gao Xinxin, Ni Qiang, Goel Renu, Xia Shuli, Ji Hongkai, Dalby Kevin N, Birnbaum Morris J, Cole Philip A, Knapp Stefan, Ryazanov Alexey G, Zack Donald J, Blackshaw Seth, Pawson Tony, Gingras Anne-Claude, Desiderio Stephen, Pandey Akhilesh, Turk Benjamin E, Zhang Jin, Zhu Heng, Qian Jiang: Construction of human activity-based phosphorylation networks. Molecular systems biology 9: 655, 2013.
Mallilankaraman Karthik, Doonan Patrick, Cárdenas César, Chandramoorthy Harish C, Müller Marioly, Miller Russell, Hoffman Nicholas E, Gandhirajan Rajesh Kumar, Molgó Jordi, Birnbaum Morris J, Rothberg Brad S, Mak Don-On Daniel, Foskett J Kevin, Madesh Muniswamy: MICU1 is an essential gatekeeper for MCU-mediated mitochondrial Ca(2+) uptake that regulates cell survival. Cell 151(3): 630-44, Oct 2012.
Quinn William J, Birnbaum Morris J: Distinct mTORC1 pathways for transcription and cleavage of SREBP-1c. Proceedings of the National Academy of Sciences of the United States of America 109(40): 15974-5, Oct 2012.
Sassu Eric D, McDermott Jacqueline E, Keys Brendan J, Esmaeili Melody, Keene Alex C, Birnbaum Morris J, DiAngelo Justin R: Mio/dChREBP coordinately increases fat mass by regulating lipid synthesis and feeding behavior in Drosophila. Biochemical and biophysical research communications 426(1): 43-8, Sep 2012.
Treins Caroline, Alliouachene Samira, Hassouna Rim, Xie Yun, Birnbaum Morris J, Pende Mario: The combined deletion of S6K1 and Akt2 deteriorates glycaemic control in high fat diet. Molecular and cellular biology 32(19): 4001-11, Jul 2012.
Sun Zheng, Miller Russell A, Patel Rajesh T, Chen Jie, Dhir Ravindra, Wang Hong, Zhang Dongyan, Graham Mark J, Unterman Terry G, Shulman Gerald I, Sztalryd Carole, Bennett Michael J, Ahima Rexford S, Birnbaum Morris J, Lazar Mitchell A: Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration. Nature medicine May 2012.
back to top
Last updated: 01/02/2014
The Trustees of the University of Pennsylvania