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Our lab explores the integration of metabolic and signaling pathways that regulate stem / progenitor cell division, fate and differentiation, primarily in neural cells. We are particularly interested in AMP-activated protein kinase (AMPK), a molecule that represents a molecular hub of metabolic control in all eukaryotic cells and functions at the crossroads of several signaling pathways. AMPK is a complex enzyme composed of multiple subunits; different combinations of those subunits allow AMPK to perform unique functions including energy and redox homeostasis, regulation of mitosis, polarity, cell migration, survival and organismal development. We are only beginning to understand the context-dependent and subunit-specific functions of AMPK.
One of our laboratory’s current goals is to understand the cellular context-dependent formation of various AMPK complexes, and how these complexes subserve unique functions of AMPK. While we appreciate that AMPK activation during acute metabolic stress reprograms cellular metabolic circuits to allow cell survival, very little is known about the functions of physiologically active AMPK. An important focus of our laboratory is to examine the functions of physiologically active AMPK in normal neural cells, stem / progenitor cells and brain cancer cells. Our long-term goals include identification of novel AMPK substrates and specific small molecule modulators of AMPK activity that could potentially have therapeutic benefits in cancer, and metabolic and neurological disorders. Read more about our research.
Xiaoli Li, Liang Li, Jie Li, Jared Sipple, Jonathan Schick, Parinda Mehta, Stella Davies, Biplab Dasgupta, Ronald Waclaw, and Qishen Pang. Concomitant inactivation of Foxo3a and Fancc or Fancd2 reveals a two-tier protection from oxidative stress. Antioxidants & Redox Signaling. 2014 Oct 20;21(12):1675-92.
Shabnam Pooya, Xiaona Liu, V.B. Sameer Kumar, Jane Anderson, Fumiyasu Imai, Wujuan Zhang, Georgianne Ciraolo, Nancy Ratner, Kenneth D. R. Setchell, Yoshida Yutaka, Michael P. Jankowski and Biplab Dasgupta*. The Tumor Suppressor LKB1 regulates Myelination through Mitochondrial Metabolism. Nature Communications. 2014 Sep 26;5:4993. *Corresponding author.
Xiaona Liu, Rishi Raj Chhipa, Ichiro Nakano and Biplab Dasgupta*. The AMPK inhibitor Compound C is a potent AMPK-independent anti-glioma agent. Molecular Cancer Therapeutics. 2014 Mar;13(3):596-605. *Corresponding author.
Lisa Ehrman, Diana Nardini, Sarah Ehrman, Tilat Rizvi, James Gulick, Maike Krenz, Biplab Dasgupta, Jeffrey Robbins, Nancy Ratner, Masato Nakafuku, and Ronald Waclaw. The protein tyrosine phosphatase Shp2 is required for the generation of oligodendrocyte progenitor cells and myelination in the mouse telencephalon. Journal of Neuroscience.2014 Mar 5;34(10):3767-78.
Swagata Karkare, Rishi Raj Chhipa, Jane Anderson, Xiaona Liu, Heather Henry, Anjelika Gasilina, Nicholas Nassar, Jayeeta Roychoudhury, Jason P Clark, Ashish Kumar, Giovanni M. Pauletti, Pradip K Ghosh and Biplab Dasgupta*. Direct inhibition of Retinoblastoma phosphorylation by Nimbolide causes cell cycle arrest and suppresses glioblastoma growth. Clinical Cancer Research. 2014 Jan 1;20(1):199-212. *Corresponding author.
Xiaona Liu, Rishi Raj Chhipa, Shabnam Pooya, Matthew Wortman, Sara Yachishin, Ashish Kumar, Lionel Chow, Xuan Zhou, Ying Sun, Brian Quinn, Christopher McPherson, Ronald Warnick, Ady Kendler, Sailendra Giri, Jeroen Poels, Koennard Nogra, Benoit Viollet, Gregory A. Grabowski and Biplab Dasgupta*. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proceedings of National Academy of Sciences, USA. 2014 Jan 28;111(4):E435-44. *Corresponding author.
Xiaona Liu, Rishi Raj Chhipa, Shabnam Pooya, Matthew Wortman, Sara Yachishin, Ashish Kumar, Lionel Chow, Xuan Zhou, Ying Sun, Brian Quinn, Christopher McPherson, Ronald Warnick, Adi Kendler, Sailendra Giri, Jeroen Poels, Koennard Nogra, Benoit Viollet, Gregory A. Grabowski and Biplab Dasgupta*. Novel mechanisms of mTOR and cdc25c regulation by AMPK agonists independent of AMPK. Proceedings of National Academy of Sciences, USA. *Corresponding author. Manuscript in Press.
Xiaona Liu, Rishi Raj Chhipa and Biplab Dasgupta*. The Selective AMPK inhibitor Compound C is a potent AMPK-independent anti-glioma agent. Molecular Cancer Therapeutics. *Corresponding author. Manuscript in Press.
Karkare S, Chhipa RR, Anderson J, Liu X, Henry H, Gasilina A, Nassar N, Roychoudhury J, Clark JP, Kumar A, Pauletti GM, Ghosh PK, Dasgupta B*. Direct inhibition of Retinoblastoma phosphorylation by Nimbolide causes cell cycle arrest and suppresses glioblastoma growth. Clinical Cancer Research. 2013 Oct 31. Epub ahead of print. *Corresponding author.
Biplab Dasgupta*, Ju Jeong Sun, Jason Gustin, Su-Ryun Jung, Kazuhiko Higasida and Jeffrey Milbrandt. The AMPK β2 subunit is required for energy homeostasis during metabolic stress. Mol Cell Biol. 2012 Jul;32(14):2837-48. Cover article. PMID: 22586267. *Corresponding author.
Dasgupta B, Milbrandt J. Resveratrol stimulates AMP kinase activity in Neurons. Proceedings of National Academy of Sciences,USA. 104:7217-22. 2007.Revollo JR, Korner A, Mills K, Satoh A, Wang T, Garten A, Dasgupta B, Townsend R, Wolberger C, Milbrandt J, Kiess W, Imai S. Nampt/PBEF/visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metabolism. 6:363-75. 2007.
Hegedus B, Dasgupta B, Eun Shin J, Emnett RJ, Hart-Mahon EK, Elghazi L, Bernal-Mizrachi E, Gutmann DH. Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms. Cell Stem Cell. 1:443-457. 2007.Dasgupta B, Gutman DH. Neurofibromin regulates neural stem cell proliferation, survival, and astroglial differentiation in vitro and in vivo. Journal of Neuroscience. 25: 5584-5594. 2005.
Dasgupta B, Yi Y, Chen DY, Weber JD, Gutmann DH. Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors. Cancer Res. 2005 Apr 1;65(7):2755-60.
Dasgupta B, Li W, Perry A, Gutmann DH. Glioma formation in Neurofibromatosis 1 reflects preferential activation of K-RAS in astrocytes. Cancer Research. 65: 236-245. 2005.
Biplab Dasgupta, PhD
Phone: 513-803-1370Email: email@example.com
Cincinnati Children's Research Horizons MagazineA Surprising Clue to Peripheral Neuropathies
Washington University Article: Well-known enzyme is unexpected contributor to brain growthFaculty of 1000 Biology Article: AMP-activated protein kinase phosphorylates retinoblastoma protein to control mammalian brain development Science Daily Article: Well-known enzyme is unexpected contributor to brain growth
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