Name of Laboratory: Laboratory for Molecular Neurodegeneration (Weebly and NUS)
Research Areas of Interest:
Aging and neurodegeneration
The current projects in my laboratory will use an integrated approach (i.e., combining molecular, cellular, biochemical, genetic and physiological techniques) by constructing in vitro and in vivo models to address the following critical issues: (1) how does aging and disease-causing mutations provoke neurodegeneration; (2) why specific neuron types are more susceptible to these disease-causing mutations, and (3) how do different cell types, such as astrocytes and oligodendrocytes, contribute to disease progression. Specifically, we will utilize different sets of transgenic mice expressing wild type and disease-linked mutations in human TDP-43, FUS/TLS and C9ORF72, including a novel model in which mouse TDP-43 is replaced with human gene. Furthermore, we will gain insight into molecular and cellular signatures of ALS-linked mutations in TDP-43, FUS/TLS and C9ORF72 with a genome-wide unbiased and quantitative approach to identify the protein and RNA interactors for these proteins.
“Converging mechanisms in ALS and FTLD: disrupted RNA or protein homeostasis.” Ling SC, Polymenidou M, Cleveland DW. Neuron, 2013: 416-438.
“ALS-linked TDP-43 mutantions produce aberrant RNA splicing and adult-onset motor disease without aggregation or loss of nuclear TDP-43.” Arnold E, Ling SC, Lagier-Tourenne C, Polymenidou M, Huelga SC, Ditsworth D, Kordasiewicz HB, McAlonis-Downes M, Platoshyn O, Parone P, Da Cruz S, Swing D, Tessarollo L, Marsala M, Shaw CE, Yeo Y, Cleveland DW. Proc Natl Acad Sci U S A, 2013: E736-745.
“Convergent roles of FUS/TLS and TDP-43 in processing RNAs with long introns.” Lagier-Tourenne C, Polymenidou M, Hutt KR, Vu AQ, Clutario K, Baughn M, Huelga, SC, Ling SC, Liang TY, Mazur C, Wancewicz E, Watt A, Freier S, Hicks GG, Donohue JP, Shiue L, Bennett CF, Ravits J, Cleveland DW, Yeo GW. Nat. Neurosci. 2012: 1488-1497
“ALS-associated mutations in TDP-43 increase its stability and promote TDP-43 complexes with FUS/TLS.” Ling SC, Albuquerque C, Han JS, Lagier-Tourenne C, Tokunaga S, Zhou H, Cleveland, DW. Proc Natl Acad Sci U S A., 2010: 13318-13323
“Transport of Drosophila fragile X mental retardation protein-containing ribonucleoprotein granules by kinesin-1 and cytoplasmic dynein” Ling SC, Fahrner PS, Greenough WT, Gelfand VI. Proc Natl Acad Sci U S A. 2004:17428-17433