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Marian  Carlson
Marian Carlson
Professor of Genetics and Development


Address: 701 West 168th Street Room 922 New York NY 10032
Phone: 212-305-6314
Fax: 212-305-1741
E-mail:

mbc1@columbia.edu

Education and Training:
Ph.D. 1978, Stanford University
Affiliations:
bullet  Department of Genetics and Development
bullet  Department of Microbiology
bullet  Institute of Cancer Research
Training Activities:
bullet  Graduate Program in Microbiology
bullet  Integrated Program in Cellular, Molecular and Biophysical Studies
bullet  Graduate Program in Genetics and Development
Research Summary:
(800 words, max)
Regulation of the Snf1/AMPK family of metabolic stress response kinases and transcriptional responses to stress in yeast.
Current Research:
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.
Publications:
(6 max)
1. 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  

2. Woods, A., K. Dickerson, R. Heath, S.-P. Hong, M. Momcilovic, S. R. Johnstone, M. Carlson and D. Carling.: (2005) Ca2+/calmodulin-dependent protein kinase kinase- beta acts upstream of AMP-activated protein kinase in mammalian cells.  Cell Metabolism  2: 21-33

3. Hong, S.-P., M. Momcilovic, and M. Carlson. : (2005) Function of mammalian LKB1 and Ca2+/calmodulin-dependent protein kinase kinase beta as Snf1-activating kinases in yeast.  J. Biol. Chem  280: 21804-21809

4. Hedbacker, K., S.-P Hong, and M. Carlson. : (2004) Pak1 protein kinase regulates activation and nuclear localization of Snf1-Gal83 protein kinase.  Mol. Cell. Biol.  8255: 8263

5. Hong, S.-P., F. C. Leiper, A. Woods, D. Carling, and M. Carlson.: (2003) Activation of yeast Snf1 and mammalian AMP-activated protein kinase by upstream kinases.  Proc. Natl. Acad. Sci. USA  100: 8839-8843

URL for lab page:
 

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