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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.
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
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, 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.
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