Office: 843-792-6949
Lab: 843-792-8906
Fax: 843-792-8568
Email: hama@musc.edu
BSB-518C

Research Interests

The research in our laboratory focuses on a class of sphingolipids containing 2-hydroxy fatty acids (hFA-sphingolipids). hFA-sphingolipids are uniquely abundant in myelin in the mammalian nervous system. The enzyme fatty acid 2-hydroxylase (FA2H) is responsible for the biosynthesis of myelin hFA-sphingolipids. Mutations in the FA2H gene cause leukodystrophy (progressive degeneration of the white matter of the brain) in children. We have developed Fa2h knockout mice as a model of the human FA2H deficiency. We are using this mouse model to develop therapeutics for the leukodystrophy. Additional projects are aimed at elucidating the mechanism of how FA2H and hFA-sphingolipids are involved in myelination, glial cell signaling, and cell differentiation.

Selected Publications

Click here to view list of publications on the National Library of Medicine's PubMed online database.

• Hama, H. Fatty acid 2-hydroxylation in mammalian sphingolipid biology. Biochim. Biophys. Acta in press
• Alderson, N.L. and Hama, H. (2009) Fatty acid 2-hydroxylase regulates cAMP-induced cell cycle exit in D6P2T Schwannoma cells. J. Lipid Res. 50, 1203-1208.
• Edvardson, S., Hama, H., Shaag, A., Gomori, J.M., Berger, I., Soffer, D., Korman, S.H., Taustein, I., Saada, A., and Elpeleg, O. (2008) Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia.  Am. J. Hum. Genet. 83, 643-648
• Ponnusamy, S., Alderson, N.L., Hama, H., Bielawski, J., Jiang, J.C., Bhandari, R., Snyder, S.H., Jazwinski, M., and Ogretmen, B. (2008) Regulation of telomere length by fatty acid elongase 3 in yeast: Involvement of inositol phosphate metabolism and ku70/80 function.  J. Biol. Chem. 283: 27514-24
• Maldonado, E.N., Alderson, N.L., Monje, P.V., Wood, P.M., and Hama, H. (2008) "FA2H is responsible for the formation of 2-hydroxy galactolipids in peripheral nervous system myelin" , J. Lipid Res. 49, 153-161.
• Uchida, Y., Hama, H. Alderson, N.L., Douangpanya, S., Wang, Y., Crumrine, D.A., Elias, P.M., and Holleran, W.M. (2007) "Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation", J. Biol. Chem 282, 13211-13219.
• Vasireddy, V., Uchida, Y., Salem, N., Kim, S.Y., Mandal, M.N., Reddy, G.B., Bodepudi, R., Alderson, N.L., Brown, J.C., Hama, H. Dlugosz, A., Elias, P.M., Holleran, W.M., Ayyagari R. (2007) "Loss of functional ELOVL4 depletes very long-chain fatty acids (>C28) and the unique ?-O-acylceramides in skin leading to neonatal death", Hum. Mol. Genet. 16, 471-482.
• Alderson, N.L., Maldonado, E.N., Kern, M.J., Bhat, N.R., and Hama, H. (2006) "FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain", J. Lipid Res 47: 2772-2780.
• Alderson, N.L., Walla, M.D. and Hama, H. (2005), "A novel method for measurement of in vitro fatty acid 2-hydroxylase activity in biological samples by gas chromatography-mass spectrometry ", J. Lipid Res.. 46:1569-1575
• Strahl, T., Hama, H., DeWald, D.B., and Thorner, J. (2005) "Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus". J. Cell Biol. 171: 967-979

• Alderson, N.L., Rembiesa, B.M., Walla, M.D., Bielawska, A., Bielawski, J., Hama, H. (2004) The Human FA2H Gene Encodes a Fatty Acid 2-Hydroxylase. J. Biol. Chem. 279: 48562-48568

• Hama, H., Torabinejad, J., Prestwich, G.D., DeWald, D.B. (2004) Measurement and immunofluorescence of cellular phosphoinositides. Methods Mol Biol. 2004;284:243-258

• Shaw, J.D., Hama, H., Sohrabi, F., DeWald, D.B., and Wendland, B. (2003) PtdIns(3,5)P2 is Required for Delivery of Endocytic Cargo into the Multivesicular Body. Traffic, 4:479-490.
• Budovskaya, Y.V., Hama, H., DeWald, D.B. and Herman, P.K. (2002) "The C-terminus of the Vps34p PI 3-kinase is necessary and sufficient for the interaction with the Vps15p protein kinase." J. Biol. Chem., 277: 287-294.
• Ha, S.-A., Bunch, J.T., Hama, H., DeWald, D.B. and Nothwehr, S.F. (2001) "A novel mechanism for localizing membrane proteins to the yeast trans-Golgi network requires function of a synaptojanin-like protein" Mol. Biol. Cell,12: 3175-3190.
• DeWald, D.B., Torabinejad, J., Jones, C.A., Shope, J.C., Cangelosi, A.R., Thompson, J.E., Prestwich, G.D., and Hama, H. (2001), "Rapid accumulation of phosphatidylinositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate correlates with calcium mobilization in salt-stressed Arabidopsis", Plant Phys. 126: 759-770.
•  Hama, H., Young, D., Radding, J., Stock, S. D., and Takemoto, J. Y. (2000), "Requirement of sphingolipid alpha-hydroxylation for fungicidal action of syringomycin E", FEBS Lett. 478: 26-28.
• Stock, S.D., Hama, H., Radding, J.A., Young, D.A., and Takemoto, J.Y. (2000), "Syringomycin E inhibition of Saccharomyces cerevisiae: Requirement for biosynthesis of sphingolipids with very long fatty acids and mannose and phosphoinositol containing head groups", Antimicrobial Agents and Chemotherapy 44: 1174-1180.
•  Hama, H., Takemoto, J.Y., and DeWald, D.B. (2000), "Analysis of phosphoinositides in protein trafficking", Methods: A Companion to Methods in Enzymology 20: 465-473.
• Hama, H., Schnieders, E.A., Thorner, J., Takemoto, J.Y., and DeWald, D.B. (1999), "Direct involvement of phosphatidylinositol 4-phosphate in secretion in the yeast Saccharomyces cerevisiae", J. Biol. Chem. 274: 34294-34300.
• Tall, G.G., Hama, H., DeWald, D.B., and Horazdovsky, B.F. (1999), "The phosphatidylinositol 3-phosphate binding protein Vac1p interacts with a Rab GTPase and a Sec1p homologue to facilitate vesicle-mediated vacuolar protein sorting", Mol. Biol. Cell 10: 1873-1889.
• Hama, H., Tall, G.G. and Horazdovsky, B.F. (1999), "Vps9p is a guanine nucleotide exchange factor involved in vesicle-mediated vacuolar protein transport", J. Biol. Chem. 274: 15284-15291.
• Stock, S.D., Hama, H., DeWald, D.B., and Takemoto, J.Y. (1999), "SEC14-dependent secretion in Saccharomyces cerevisiae: non-dependence on sphingolipid synthesis-coupled diacylglycerol production", J. Biol. Chem. 274: 12979-12983.