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Marian Carlson
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Professor of Genetics and Development
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| Address: |
701 West 168th Street Room 1412 New York NY 10032 |
| Phone: |
212-305-3851 |
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E-mail:
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mbc1@columbia.edu
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Education and Training:
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Ph.D. 1978, Stanford University
Postdoctoral Fellow 1978-1981, MIT
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Affiliations:
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Department of Genetics and Development
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Training Activities:
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Integrated Program in Cellular, Molecular and Biophysical Studies
Graduate Program in Genetics and Development
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Research Summary:
(800 words, max)
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Regulation of the Snf1/AMPK family of metabolic stress response kinases and transcriptional responses to stress in yeast. |
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Current Research:
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Our research focuses on the Snf1/AMP-activated protein kinase (AMPK) family, which is essential for stress responses in all eukaryotes. In humans, AMPK has broad roles in responses to metabolic stress and has been implicated in type 2 diabetes, obesity, and cardiovascular disease. In the yeast Saccharomyces cerevisiae, Snf1 protein kinase regulates transcription, metabolism, and developmental processes in response to nutrient starvation and other stresses. We are interested in the regulation of Snf1/AMPK pathways, with respect to both catalytic activity and subcellular localization. We identified the first upstream kinases for Snf1/AMPK: three yeast kinases and the mammalian tumor suppressor kinase LKB1 and CaMKK, which activate AMPK. We found that both LKB1 and CaMKK function in yeast to activate Snf1. This heterologous function has provided the basis for a powerful genetic selection in yeast for mammalian AMPK kinases, which are potential therapeutic targets. We are currrently exploiting this selection to identify new AMPK kinases, and we recently identified TGF-beta-activated kinase (TAK1), a member of the MAPKKK family that is activated by cytokines and bacterial lipopolysaccharide. Evidence supports TAK1 as a candidate for an authentic AMPK kinase in mammalian cells, and further studies are underway. |
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Publications:
(6 max)
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1. Ruiz, A., X. Xu and M. Carlson: (2011) Roles of two protein phosphatases, Reg1-Glc7 and Sit4, and glycogen synthesis in regulation of SNF1 protein kinase. Proc. Natl. Acad. Sci. USA 108: 6349-6354.
2. Momcilovic, M. and M. Carlson: (2011) Alterations at dispersed sites cause phosphorylation and activation of SNF1 protein kinase during growth on high glucose. J. Biol. Chem 286: 23544-23551.
3. Liu, Y., X. Xu and M. Carlson: (2011) Interaction of SNF1 protein kinase with its activating kinase Sak1. Eukaryot 10: 313-319.
4. Momcilovic, M., S. H. Iram, Y. Liu and M. Carlson: (2008) Roles of the glycogen-binding domain and Snf4 in glucose inhibition of SNF1 protein kinase. J. Biol. Chem 283: 19521-19529.
5. Hong, S.-P. and M. Carlson: (2007) Regulation of Snf1 protein kinase in response to environmental stress . J. Biol. Chem 282: 16838-45.
6. Momcilovic, M., S.-P. Hong, and M. Carlson: (2006) Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMPK in vitro. J. Biol. Chem 281: 25336-25343.
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URL for lab page:
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