教育经历

1988.9-1992.7  北京大学生物系 学士学位

1992.8-1995.7  中国医学科学院基础医学研究所 硕士学位

1995.8-2000.12  德克萨斯大学西南医学中心 博士学位

工作经历

2001.1-2002.12 德克萨斯大学西南医学中心 博士后

2003.1-2009.8 麻省理工学院生物系 博士后

2009.8-现在 澳门新葡官网进入澳门新莆京7906not 教授

社会兼职

美国遗传学会会员

中国核糖核酸学会理事

学术奖励

The Charles A. King Medical Foundation Fellowship, 2004-2005

教育部新世纪优秀人才，2010

研究方向

遗传学，分子生物学，神经生物学，人类疾病的分子遗传机制和动物模型研究

研究简介

1.RNA剪接的分子机制与异常RNA剪接引起的人类疾病

RNA剪接是真核基因表达的主要调控机制。目前已发现数百种剪接因子，但是对剪接因子的体内功能和相互作用了解依然很少。我们鉴定了关键剪接因子U2AF大亚基 (UAF-1)，SF1/BBP(SFA-1)， MFAP-1, RBM-5, PRP-8, PRP-6的线虫（Caenorhabditis elegans, C. elegans）同源基因的一系列突变体。利用这些遗传学工具，我们正在研究包括脊髓肌肉萎缩症(SMA)，视网膜色素变性(RP)，癌症发生过程中剪接因子的功能。

2.动物行为的分子，遗传和神经回路机制。

水杨酸甲酯（Methyl salicylate，MeSa）是一种挥发性的多功能植物激素。我们以线虫作为生物模型，发现野生型的线虫对于MeSa表现出强烈的逃避反应。我们发现了四个编码NCA/NALCN离子通道的基因调控线虫对MeSa的逃避。NALCN基因的突变与许多疾病密切相关。通过对这些基因的功能以及相互之间作用的研究，可以阐明MeSa影响线虫行为的分子以及神经机制，获得对NALCN相关疾病新的认识。

3.氧化自由基及氧化压力的分子遗传机制

氧化自由基（Reactive oxygen species，ROS）是生命活动中重要的活性分子，广泛参与细胞的基本生命过程和信号传导，其稳态的异常可导致多种疾病。我们用线虫研究微量元素碘摄入过量所导致生理变化的分子机制，发现过量碘可以诱导线虫体内氧化自由基的急剧上升并导致发育缺陷。通过遗传筛选，我们发现了至少5个调控ROS生成和稳态的基因，将为ROS稳态调控和过量碘相关疾病的分子机制提供新的认识。

4.人类疾病小鼠模型的建立和分析。

和临床医生合作，我们正在分析几个强直性脊柱炎和神经退行性疾病的候选致病基因，并构建小鼠疾病模型用于病理机制的研究。

发表论文

Ma L.,* Reis G.,* Parada LF., Schuman EM. (1999). Neuronal NT-3 is not required for synaptic transmission or long-term potentiation in area CA1 of the adult mouse hippocampus. Learning & Memory, 6: 267-275. (* Equal contribution)

Ma L., Merenmies J., Parada LF. (2000). Molecular characterization of the TrkA/NGF receptor minimal enhancer reveals regulation by multiple cis elements to drive embryonic neuron expression. Development, 127: 3777-3788.

Lei L., Ma L., Nef S., Thai T., Parada LF. (2001). mKLF7, a potential transcriptional regulator of TrkA nerve growth factor receptor expression in sensory and sympathetic neurons. Development, 128:1147-1158.

Ma L., Harada T., Harada C., Romero MI., Hebert JM., McConnell, SK., Parada, LF. (2002). Neurotrophin-3 is required for appropriate establishment of thalamocortical connections. Neuron, 36: 623-34.

Ma L., Lei L., Raisa Eng S., Turner E., Parada LF. (2003). Brn3a regulation of TrkA/NGF receptor expression in developing sensory neurons. Development, 130: 3525-34.

Lush M., Ma L. Parada LF. (2005). TrkB signaling regulates the developmental maturation of the somatosensory cortex. Int J Dev Neurosci, 23(6): 523-36.

Ma L,, Horvitz HR. (2009). Mutations in the Caenorhabditis elegans U2AF large subunit UAF-1 alter the choice of a 3′ splice site in vivo. PLOS Genet 5(11): e1000708. doi:10.1371/journal.pgen.1000708

Wang F., Huang S., Ma L.* (2010). Caenorhabditis elegans operons contain a higher proportion of genes with multiple transcripts and use 3′ splice sites differentially. PLOS ONE 5(8): e12456. doi:10.1371/journal.pone.0012456 (* Corresponding author)

Ma L.,* Tan Z.,* Teng Y., Hoersch S., Horvitz HR. (2011). In vivo effects on intron retention and exon skipping by the U2AF large subunit and SF1/BBP in the nematode Caenorhabditis elegans. RNA 17(11): 2001-11 (* Equal contribution)

Lu J, Tan J, Durairajan S, Liu L, Zhang Z, Ma L, Shen H, Chan H, Li M. (2012). Isorhynchophylline, a natural alkaloid, promotes the degradation of alpha-synuclein in neuronal cells via inducing autophagy. Autophagy. 8(1): 98-108.

Ma L.,* Gao X., Luo J., Huang L., Teng Y., Horvitz HR.* (2012). The Caenorhabditis elegans gene mfap-1 encodes a nuclear protein that affects alternative splicing. PLOS Genet 8(7): e1002827. doi:10.1371/journal.pgen.1002827 (* Co-corresponding authors)

de la Cruz IP., Ma L., Horvitz HR. (2014). The Caenorhabditis elegans iodotyrosine deiodinase ortholog SUP-18 functions through a conserved channel SC-box to regulate the muscle two-pore domain potassium channel SUP-9. PLOS Genet 10(2): e1004175. doi:10.1371/journal.pgen.1004175.

Yuan, D., Zhu, Z., Tan, X., Liang, J., Zeng, C., Zhang, J., Chen, J., Ma, L., Dogan, A., Brockmann, G., Medina, E., Rice, A.D., Moyer, R.W., Man, X., Yi, K., Li, Y., Lu, Q., Huang, Y., and Huang, S. (2014). Scoring the collective effects of SNPs: associations of minor alleles with complex traits in model organisms. Sci China Life Sci. 10.1007/s11427-014-4704-4

Edens BM., Ajroud-Driss S., Ma L., Ma Y. (2014). Molecular mechanisms and animal models of spinal muscular atrophy. BBA - Molecular Basis of Disease (Review) 1852(4): 685-692.

Gao X., Teng Y., Luo J., Huang L., Li M., Zhang Z., Ma Y., Ma L.* (2014). The survival motor neuron gene smn-1 interacts with the U2AF large subunit gene uaf-1 to regulate Caenorhabditis elegans lifespan and motor functions. RNA Biology 11(9): 1148-60. (* Corresponding author)

Xu Z., Luo J., Li Y., Ma L.* (2015). The BLI-3/TSP-15/DOXA-1 dual oxidase complex is required for iodide toxicity in C. elegans. G3: Genes, Genomes, Genetics 5(2): 195-203. (* Corresponding author)

Luo J., Xu Z., Tan Z., Zhang Z., Ma L.* (2015). Neuropeptide receptors NPR-1 and NPR-2 regulate C. elegans avoidance response to the plant stress hormone methyl salicylate. Genetics 199(2): 523-31. (* Corresponding author)

Miller N., Feng Z., Edens B., Yang B., Shi H., Sze C., Hong B., Su S., Cantu J., Topczewski J., Crawford T., Ko CP., Sumner C., Ma L., Ma Y. (2015). Non-aggregating tau phosphorylation by Cdk5 contributes to motor neuron degeneration in spinal muscular atrophy. Journal of Neuroscience 35(15): 6038-50.

Wu B., Xiao K., Zhang Z., Ma L. * (2016). Altered expression of EPO might underlie hepatic hemangiomas in LRRK2 knockout mice. BioMed Research International 2016 (2016), Article ID 7681259. (* Corresponding author)

Wei X., Gao H., Zou J., Liu X., Chen D., Liao J., Xu Y., Ma L., Tang B., Zhang Z., Cai X., Jin K., Xia Y., Wang Q. (2016). Contra-directional coupling of Nur77 and Nurr1 in neurodegeneration: A novel mechanism for memantine-induced anti-inflammation and anti-mitochondrial Impairment. Mol Neurobiol. 53(9):5876-5892

Tan Z.*, Zeng H., Xu Z., Tian Q., Gao X., Zhou C., Zheng Y., Wang J., Ling G., Wang B., Yang Y., Ma L. * (2018). Identification of ANKDD1B variants in an ankylosing spondylitis pedigree and a sporadic patient. BMC Medical Genetics19(1):111. doi: 10.1186/s12881-018-0622-9. (* Co-corresponding authors)