The major emphasis of my research involves studying the TRP- (transient receptor potential) ML subfamily and how defects in these organelle cation channels lead to altered vesicle trafficking and neurodegeneration. Mutations in TRP-ML1 lead to MLIV, an autosomal recessive lysosomal storage disease with clinical manifestations of profound pyschomotor and mental retardation. Mutations in the third member of this family, TRP-ML3, lead to the varitint-waddler phenotype in mice, which is characterized by hearing loss, pigmentation defects and increased mortality. We are using a combination of biochemical, molecular, confocal imaging and electrophysiological methods to characterize the properties of these channels, their localization and function.
RESEARCH INTERESTS
TRP-ML cation channels
Mucolipidosis type IV (MLIV)
RECENT PUBLICATIONS
Katkade V, Soyombo AA, Isordia-Salas I, Bradford HN, Gaughan JP, Colman RW, Panetti TS, "Domain 5 of cleaved high molecular weight kininogen inhibits endothelial cell migration through Akt." Thromb Haemost, 94(3):606-14, September 2005
Kiselyov K, Chen J, Rbaibi Y, Oberdick D, Tjon-Kon-Sang S, Shcheynikov N, Muallem S, Soyombo A, "TRP-ML1 is a lysosomal monovalent cation channel that undergoes proteolytic cleavage." J Biol Chem, 280(52):43218-23, December 2005
Soyombo AA, Tjon-Kon-Sang S, Rbaibi Y, Bashllari E, Bisceglia J, Muallem S, Kiselyov K, "TRP-ML1 regulates lysosomal pH and acidic lysosomal lipid hydrolytic activity." J Biol Chem, 281(11):7294-301, March 2006
Wang Y, Soyombo AA, Shcheynikov N, Zeng W, Dorwart M, Marino CR, Thomas PJ, Muallem S, "Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO(3)(-) secretion: relevance to cystic fibrosis." EMBO J, [Epub ahead of print] October 2006
Kim HJ, Li Q, Tjon-Kon-Sang S, So I, Kiselyov K, Soyombo AA, Muallem S, "A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype" EMBO J, 27(8):1197-205, April 2008
SIGNIFICANT PUBLICATIONS
Soyombo AA, Yi W, Hofmann SL, "Structure of the human palmitoyl-protein thioesterase-2 gene (PPT2) in the major histocompatibility complex on chromosome 6p21.3." Genomics, 56(2):208-16, March 1999
Gupta P, Soyombo AA, Atashband A, Wisniewski KE, Shelton JM, Richardson JA, Hammer RE, Hofmann SL, "Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice." Proc Natl Acad Sci U S A, 98(24):13566-71, November 2001
Gupta P, Soyombo AA, Shelton JM, Wilkofsky IG, Wisniewski KE, Richardson JA, Hofmann SL, "Disruption of PPT2 in mice causes an unusual lysosomal storage disorder with neurovisceral features." Proc Natl Acad Sci U S A, 100(21):12325-30, October 2003
Ko SB, Zeng W, Dorwart MR, Luo X, Kim KH, Millen L, Goto H, Naruse S, Soyombo A, Thomas PJ, Muallem S, "Gating of CFTR by the STAS domain of SLC26 transporters." Nat Cell Biol, 6(4):343-50, April 2004
Wang S, Zeng W, Soyombo AA, Tang W, Ross EM, Barnes AP, Milgram SL, Penninger JM, Allen PB, Greengard P, Muallem S, "Spinophilin regulates Ca2+ signalling by binding the N-terminal domain of RGS2 and the third intracellular loop of G-protein-coupled receptors." Nature Cell Biology, 7/4:405-11, April 2005
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