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Dean R Appling
Professor Emeritus
Molecular BiosciencesRegulation And Organization Of Metabolic Pathways-
Regulation And Organization Of Metabolic Pathways
My laboratory studies the organization and regulation of metabolic pathways in eukaryotes. Eukaryotic cells are composed of many different compartments, such as cytoplasm, mitochondria, and nuclei. Although each of these compartments exhibits a distinct set of metabolic processes, they must all communicate with each other for the cell to function properly. Understanding how these processes are organized and controlled represents the next frontier in the study of metabolism. We have focused our efforts on folate-mediated one-carbon metabolism. This set of pathways is found in all cells and organisms, is central to fundamental processes such as nucleic acid and protein synthesis, and occurs in multiple compartments. We are particularly interested in understanding how one-carbon metabolism is organized in mitochondria, as these organelles are central players in many human diseases. We utilize a wide variety of biochemical and molecular genetic techniques, including metabolic engineering, to study the organization of these pathways in both mammalian and fungal systems. We are currently using knockout mouse models to study the role of these pathways in embryonic development.
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Representative Publications
Momb, J., and Appling, D.R. (2014) "Mitochondrial One-Carbon Metabolism and Neural Tube Defects" Birth Defects Research Part A: Clinical and Molecular Teratology 100, 576-583 [BDRA Online]Shin, M., Bryant, J.D., Momb, J., and Appling, D.R. (2014) “Mitochondrial MTHFD2L is a Dual Redox Cofactor Specific Methylenetetrahydrofolate Dehydrogenase/Methenyltetrahydrofolate Cyclohydrolase Expressed in Both Adult and Embryonic Tissues” J. Biol. Chem. 289, 15507-15517 [JBC Online]
Momb, J. Lewandowski, J.P., Bryant, J.D., Fitch, R., Surman, D.R., Vokes, S.A., and Appling, D.R. (2013) “Deletion of Mthfd1l Causes Embryonic Lethality and Neural Tube and Craniofacial Defects in Mice” Proc. Natl. Acad. Sci. USA 110, 549-554 [PNAS Online]
Bolusani, S., Young, B.A., Cole, N.A., Tibbetts, A.S., Momb, J., Bryant, J.D., Solmonson, A., and Appling, D.R. (2011) "Mammalian MTHFD2L encodes a mitochondrial methylenetetrahydrofolate dehydrogenase isozyme expressed in adult tissues" J. Biol. Chem. 286, 5166-5174 [JBC Online]
Tibbetts, A.S. and Appling, D. R. (2010) “Compartmentalization of Mammalian Folate-Mediated One-Carbon Metabolism” Ann. Rev. Nutrition 30: 57-81. [ARN Online]
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