Douglas Lyne Black

Professor, MIMG, University of California Los Angeles

(310) 794-7689

We are interested in how cells process genetic information to form the messenger RNAs (mRNAs) that encode proteins, and our primary focus is the regulation of the pre-mRNA splicing reaction. In producing multiple mRNAs and proteins from a single DNA gene, alternative splicing is a key mechanism for creating the specialized functions of cells. This mode of gene regulation is particularly prevalent in the mammalian nervous system, where it contributes to the enormous diversity of neuronal cells. Errors in RNA splicing and its regulation also contribute to many aspects of human disease, including cancer, neurodegeneration, and inherited genetic disorders. In studying a variety of biological systems and applying a wide range of molecular approaches, our common goal is to develop a mechanistic understanding of gene regulation at the RNA level, and ultimately apply this knowledge to human health.

Interests

Posttranscriptional gene regulation in neurons, RNA metabolism in mammalian cells, Structure and function of RNA binding proteins and RNP complexes, regulation of pre-mRNA splicing

Education and Training

Yale UniversityPhD06/1987Molecular Biophysics and Biochemistry
University of CaliforniaBA06/1982Chemistry

Publications

  1. Xiao W, Halabi R, Lin CH, Nazim M, Yeom KH, Black DL. The lncRNA Malat1 is trafficked to the cytoplasm as a localized mRNA encoding a small peptide in neurons.. bioRxiv : the preprint server for biology, 2024.
  2. Tang AA, Afasizheva A, Cano CT, Plath K, Black D, Franco E. Optimization of RNA Pepper Sensors for the Detection of Arbitrary RNA Targets.. ACS synthetic biology, 2024.
  3. Achiro JM, Tao Y, Gao F, Lin CH, Watanabe M, Neumann S, Coppola G, Black DL, Martin KC. Aging differentially alters the transcriptome and landscape of chromatin accessibility in the male and female mouse hippocampus.. Frontiers in molecular neuroscience, 2024.
  4. Dror I, Chitiashvili T, Tan SYX, Cano CT, Sahakyan A, Markaki Y, Chronis C, Collier AJ, Deng W, Liang G, Sun Y, Afasizheva A, Miller J, Xiao W, Black DL, Ding F, Plath K. XIST directly regulates X-linked and autosomal genes in naive human pluripotent cells.. Cell, 2024.
  5. Damianov A, Lin CH, Huang J, Zhou L, Jami-Alahmadi Y, Wohlschlegel J, Black DL. The apoptotic splicing regulators RBM5 and RBM10 are subunits of the U2 snRNP engaged with intron branch sites on chromatin.. bioRxiv : the preprint server for biology, 2023.
  6. Chen X, Yang HT, Zhang B, Phillips JW, Cheng D, Rigo F, Witte ON, Xing Y, Black DL. The RNA-binding proteins hnRNP H and F regulate splicing of a MYC-dependent HRAS exon in prostate cancer cells.. Proceedings of the National Academy of Sciences of the United States of America, 2023.
  7. Xiao W, Yeom KH, Lin CH, Black DL. Improved enzymatic labeling of fluorescent in situ hybridization probes applied to the visualization of retained introns in cells.. RNA (New York, N.Y.), 2023.
  8. Qian K, Tol MJ, Wu J, Uchiyama LF, Xiao X, Cui L, Bedard AH, Weston TA, Rajendran PS, Vergnes L, Shimanaka Y, Yin Y, Jami-Alahmadi Y, Cohn W, Bajar BT, Lin CH, Jin B, DeNardo LA, Black DL, Whitelegge JP, Wohlschlegel JA, Reue K, Shivkumar K, Chen FJ, Young SG, Li P, Tontonoz P. CLSTN3β enforces adipocyte multilocularity to facilitate lipid utilization.. Nature, 2022.
  9. Yeom KH, Pan Z, Lin CH, Lim HY, Xiao W, Xing Y, Black DL. Tracking pre-mRNA maturation across subcellular compartments identifies developmental gene regulation through intron retention and nuclear anchoring.. Genome research, 2021.
  10. Pandya-Jones A, Markaki Y, Serizay J, Chitiashvili T, Leon WRM, Damianov A, Chronis C, Papp B, Chen CK, McKee R, Wang XJ, Chau A, Sabri S, Leonhardt H, Zheng S, Guttman M, Black DL, Plath K. Publisher Correction: A protein assembly mediates Xist localization and gene silencing.. Nature, 2020.
  11. Pandya-Jones A, Markaki Y, Serizay J, Chitiashvili T, Mancia Leon WR, Damianov A, Chronis C, Papp B, Chen CK, McKee R, Wang XJ, Chau A, Sabri S, Leonhardt H, Zheng S, Guttman M, Black DL, Plath K. A protein assembly mediates Xist localization and gene silencing.. Nature, 2020.
  12. Phillips JW, Pan Y, Tsai BL, Xie Z, Demirdjian L, Xiao W, Yang HT, Zhang Y, Lin CH, Cheng D, Hu Q, Liu S, Black DL, Witte ON, Xing Y. Pathway-guided analysis identifies Myc-dependent alternative pre-mRNA splicing in aggressive prostate cancers.. Proceedings of the National Academy of Sciences of the United States of America, 2020.
  13. Zhang Z, Pan Z, Ying Y, Xie Z, Adhikari S, Phillips J, Carstens RP, Black DL, Wu Y, Xing Y. Deep-learning augmented RNA-seq analysis of transcript splicing.. Nature methods, 2019.
  14. Cao Q, Shin WS, Chan H, Vuong CK, Dubois B, Li B, Murray KA, Sawaya MR, Feigon J, Black DL, Eisenberg DS, Jiang L. Author Correction: Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design.. Nature chemistry, 2018.
  15. Yeom KH, Mitchell S, Linares AJ, Zheng S, Lin CH, Wang XJ, Hoffmann A, Black DL. Polypyrimidine tract-binding protein blocks miRNA-124 biogenesis to enforce its neuronal-specific expression in the mouse.. Proceedings of the National Academy of Sciences of the United States of America, 2018.
  16. Cao Q, Shin WS, Chan H, Vuong CK, Dubois B, Li B, Murray KA, Sawaya MR, Feigon J, Black DL, Eisenberg DS, Jiang L. Inhibiting amyloid-β cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design.. Nature chemistry, 2018.
  17. Vuong CK, Wei W, Lee JA, Lin CH, Damianov A, de la Torre-Ubieta L, Halabi R, Otis KO, Martin KC, O'Dell TJ, Black DL. Rbfox1 Regulates Synaptic Transmission through the Inhibitory Neuron-Specific vSNARE Vamp1.. Neuron, 2018.
  18. Li Q, Zheng S, Han A, Lin CH, Stoilov P, Fu XD, Black DL. Correction: The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation.. eLife, 2017.
  19. Ying Y, Wang XJ, Vuong CK, Lin CH, Damianov A, Black DL. Splicing Activation by Rbfox Requires Self-Aggregation through Its Tyrosine-Rich Domain.. Cell, 2017.
  20. Ke S, Pandya-Jones A, Saito Y, Fak JJ, Vågbø CB, Geula S, Hanna JH, Black DL, Darnell JE, Darnell RB. m6A mRNA modifications are deposited in nascent pre-mRNA and are not required for splicing but do specify cytoplasmic turnover.. Genes & development, 2017.
  21. Wang J, Rajbhandari P, Damianov A, Han A, Sallam T, Waki H, Villanueva CJ, Lee SD, Nielsen R, Mandrup S, Reue K, Young SG, Whitelegge J, Saez E, Black DL, Tontonoz P. RNA-binding protein PSPC1 promotes the differentiation-dependent nuclear export of adipocyte RNAs.. The Journal of clinical investigation, 2017.
  22. Vuong JK, Lin CH, Zhang M, Chen L, Black DL, Zheng S. PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing.. Cell reports, 2016.
  23. Wongpalee SP, Vashisht A, Sharma S, Chui D, Wohlschlegel JA, Black DL. Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing.. eLife, 2016.
  24. Zhang X, Chen MH, Wu X, Kodani A, Fan J, Doan R, Ozawa M, Ma J, Yoshida N, Reiter JF, Black DL, Kharchenko PV, Sharp PA, Walsh CA. Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex.. Cell, 2016.
  25. Keppetipola NM, Yeom KH, Hernandez AL, Bui T, Sharma S, Black DL. Multiple determinants of splicing repression activity in the polypyrimidine tract binding proteins, PTBP1 and PTBP2.. RNA (New York, N.Y.), 2016.
  26. Vuong CK, Black DL, Zheng S. The neurogenetics of alternative splicing.. Nature reviews. Neuroscience, 2016.
  27. Damianov A, Ying Y, Lin CH, Lee JA, Tran D, Vashisht AA, Bahrami-Samani E, Xing Y, Martin KC, Wohlschlegel JA, Black DL. Rbfox Proteins Regulate Splicing as Part of a Large Multiprotein Complex LASR.. Cell, 2016.
  28. Linares AJ, Lin CH, Damianov A, Adams KL, Novitch BG, Black DL. The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation.. eLife, 2015.
  29. Lee JA, Damianov A, Lin CH, Fontes M, Parikshak NN, Anderson ES, Geschwind DH, Black DL, Martin KC. Cytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes.. Neuron, 2015.
  30. Black D. Reflections on the RNA journal at 20 and its role in the question of splice site choice.. RNA (New York, N.Y.), 2015.
  31. Sharma S, Wongpalee SP, Vashisht A, Wohlschlegel JA, Black DL. Stem-loop 4 of U1 snRNA is essential for splicing and interacts with the U2 snRNP-specific SF3A1 protein during spliceosome assembly.. Genes & development, 2014.
  32. Han A, Stoilov P, Linares AJ, Zhou Y, Fu XD, Black DL. De novo prediction of PTBP1 binding and splicing targets reveals unexpected features of its RNA recognition and function.. PLoS computational biology, 2014.
  33. Li Q, Zheng S, Han A, Lin CH, Stoilov P, Fu XD, Black DL. The splicing regulator PTBP2 controls a program of embryonic splicing required for neuronal maturation.. eLife, 2014.
  34. Lovci MT, Ghanem D, Marr H, Arnold J, Gee S, Parra M, Liang TY, Stark TJ, Gehman LT, Hoon S, Massirer KB, Pratt GA, Black DL, Gray JW, Conboy JG, Yeo GW. Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges.. Nature structural & molecular biology, 2013.
  35. Babic I, Anderson ES, Tanaka K, Guo D, Masui K, Li B, Zhu S, Gu Y, Villa GR, Akhavan D, Nathanson D, Gini B, Mareninov S, Li R, Camacho CE, Kurdistani SK, Eskin A, Nelson SF, Yong WH, Cavenee WK, Cloughesy TF, Christofk HR, Black DL, Mischel PS. EGFR mutation-induced alternative splicing of Max contributes to growth of glycolytic tumors in brain cancer.. Cell metabolism, 2013.
  36. Zheng S, Black DL. Alternative pre-mRNA splicing in neurons: growing up and extending its reach.. Trends in genetics : TIG, 2013.
  37. Zheng S, Damoiseaux R, Chen L, Black DL. A broadly applicable high-throughput screening strategy identifies new regulators of Dlg4 (Psd-95) alternative splicing.. Genome research, 2013.
  38. Pandya-Jones A, Bhatt DM, Lin CH, Tong AJ, Smale ST, Black DL. Splicing kinetics and transcript release from the chromatin compartment limit the rate of Lipid A-induced gene expression.. RNA (New York, N.Y.), 2013.
  39. Bhatt DM, Pandya-Jones A, Tong AJ, Barozzi I, Lissner MM, Natoli G, Black DL, Smale ST. Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions.. Cell, 2012.
  40. Keppetipola N, Sharma S, Li Q, Black DL. Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2.. Critical reviews in biochemistry and molecular biology, 2012.
  41. Anderson ES, Lin CH, Xiao X, Stoilov P, Burge CB, Black DL. The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B.. RNA (New York, N.Y.), 2012.
  42. Gehman LT, Meera P, Stoilov P, Shiue L, O'Brien JE, Meisler MH, Ares M, Otis TS, Black DL. The splicing regulator Rbfox2 is required for both cerebellar development and mature motor function.. Genes & development, 2012.
  43. Zheng S, Gray EE, Chawla G, Porse BT, O'Dell TJ, Black DL. PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2.. Nature neuroscience, 2012.
  44. Gehman LT, Stoilov P, Maguire J, Damianov A, Lin CH, Shiue L, Ares M, Mody I, Black DL. The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain.. Nature genetics, 2011.
  45. Sharma S, Maris C, Allain FH, Black DL. U1 snRNA directly interacts with polypyrimidine tract-binding protein during splicing repression.. Molecular cell, 2011.
  46. Tang ZZ, Sharma S, Zheng S, Chawla G, Nikolic J, Black DL. Regulation of the mutually exclusive exons 8a and 8 in the CaV1.2 calcium channel transcript by polypyrimidine tract-binding protein.. The Journal of biological chemistry, 2011.
  47. Black DL, Gorospe M. Tapas and RNA in Renaissance Spain.. RNA biology, 2010.
  48. Damianov A, Black DL. Autoregulation of Fox protein expression to produce dominant negative splicing factors.. RNA (New York, N.Y.), 2009.
  49. Xue Y, Zhou Y, Wu T, Zhu T, Ji X, Kwon YS, Zhang C, Yeo G, Black DL, Sun H, Fu XD, Zhang Y. Genome-wide analysis of PTB-RNA interactions reveals a strategy used by the general splicing repressor to modulate exon inclusion or skipping.. Molecular cell, 2009.
  50. Lee JA, Tang ZZ, Black DL. An inducible change in Fox-1/A2BP1 splicing modulates the alternative splicing of downstream neuronal target exons.. Genes & development, 2009.
  51. Babic I, Sharma S, Black DL. A role for polypyrimidine tract binding protein in the establishment of focal adhesions.. Molecular and cellular biology, 2009.
  52. Pandya-Jones A, Black DL. Co-transcriptional splicing of constitutive and alternative exons.. RNA (New York, N.Y.), 2009.
  53. Tang ZZ, Zheng S, Nikolic J, Black DL. Developmental control of CaV1.2 L-type calcium channel splicing by Fox proteins.. Molecular and cellular biology, 2009.
  54. Chawla G, Lin CH, Han A, Shiue L, Ares M, Black DL. Sam68 regulates a set of alternatively spliced exons during neurogenesis.. Molecular and cellular biology, 2008.
  55. Stoilov P, Lin CH, Damoiseaux R, Nikolic J, Black DL. A high-throughput screening strategy identifies cardiotonic steroids as alternative splicing modulators.. Proceedings of the National Academy of Sciences of the United States of America, 2008.
  56. Xing Y, Stoilov P, Kapur K, Han A, Jiang H, Shen S, Black DL, Wong WH. MADS: a new and improved method for analysis of differential alternative splicing by exon-tiling microarrays.. RNA (New York, N.Y.), 2008.
  57. Black DL, Zipursky SL. To cross or not to cross: alternatively spliced forms of the Robo3 receptor regulate discrete steps in axonal midline crossing.. Neuron, 2008.
  58. Sharma S, Kohlstaedt LA, Damianov A, Rio DC, Black DL. Polypyrimidine tract binding protein controls the transition from exon definition to an intron defined spliceosome.. Nature structural & molecular biology, 2008.
  59. Li Q, Lee JA, Black DL. Neuronal regulation of alternative pre-mRNA splicing.. Nature reviews. Neuroscience, 2007.
  60. Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, Shiue L, Ares M, Black DL. A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons.. Genes & development, 2007.
  61. Lee JA, Xing Y, Nguyen D, Xie J, Lee CJ, Black DL. Depolarization and CaM kinase IV modulate NMDA receptor splicing through two essential RNA elements.. PLoS biology, 2007.
  62. Boutz PL, Chawla G, Stoilov P, Black DL. MicroRNAs regulate the expression of the alternative splicing factor nPTB during muscle development.. Genes & development, 2007.
  63. Sharma S, Black DL. Maps, codes, and sequence elements: can we predict the protein output from an alternatively spliced locus?. Neuron, 2006.
  64. Black DL, Graveley BR. Splicing bioinformatics to biology.. Genome biology, 2006.
  65. Auweter SD, Fasan R, Reymond L, Underwood JG, Black DL, Pitsch S, Allain FH. Molecular basis of RNA recognition by the human alternative splicing factor Fox-1.. The EMBO journal, 2005.
  66. Xie J, Jan C, Stoilov P, Park J, Black DL. A consensus CaMK IV-responsive RNA sequence mediates regulation of alternative exons in neurons.. RNA (New York, N.Y.), 2005.
  67. Underwood JG, Boutz PL, Dougherty JD, Stoilov P, Black DL. Homologues of the Caenorhabditis elegans Fox-1 protein are neuronal splicing regulators in mammals.. Molecular and cellular biology, 2005.
  68. Oberstrass FC, Auweter SD, Erat M, Hargous Y, Henning A, Wenter P, Reymond L, Amir-Ahmady B, Pitsch S, Black DL, Allain FH. Structure of PTB bound to RNA: specific binding and implications for splicing regulation.. Science (New York, N.Y.), 2005.
  69. Sharma S, Falick AM, Black DL. Polypyrimidine tract binding protein blocks the 5' splice site-dependent assembly of U2AF and the prespliceosomal E complex.. Molecular cell, 2005.
  70. Amir-Ahmady B, Boutz PL, Markovtsov V, Phillips ML, Black DL. Exon repression by polypyrimidine tract binding protein.. RNA (New York, N.Y.), 2005.
  71. Black DL. A simple answer for a splicing conundrum.. Proceedings of the National Academy of Sciences of the United States of America, 2005.
  72. Hall MP, Huang S, Black DL. Differentiation-induced colocalization of the KH-type splicing regulatory protein with polypyrimidine tract binding protein and the c-src pre-mRNA.. Molecular biology of the cell, 2003.
  73. Xie J, Lee JA, Kress TL, Mowry KL, Black DL. Protein kinase A phosphorylation modulates transport of the polypyrimidine tract-binding protein.. Proceedings of the National Academy of Sciences of the United States of America, 2003.
  74. Rooke N, Markovtsov V, Cagavi E, Black DL. Roles for SR proteins and hnRNP A1 in the regulation of c-src exon N1.. Molecular and cellular biology, 2003.
  75. Black DL. Mechanisms of alternative pre-messenger RNA splicing.. Annual review of biochemistry, 2003.