Posts classified under: B

Dean Bok, Ph.D.

Biography

Retinal Cell and Molecular Biology Dr. Bok studies mechanisms whereby membrane receptors, retinoid binding proteins, and enzymes mediate the vectorial uptake, processing and release of retinoids by the retinal pigment epithelium (RPE). He also explores mechanisms whereby the RPE cells develop the polarity required for their diverse functions. A second major research effort involves the study of molecular mechanisms underlying degeneration of retinal photoreceptors. These degenerations come under the general disease categories of retinitis pigmentosa and macular degeneration in humans. Retinitis pigmentosa is a family of inherited blinding diseases. Macular degeneration can be either age related or inherited. The third field of study involves photoreceptor-RPE interactions in health and disease. This includes the development of transgenic mice in which the expression of a wild-type gene or its mutant counterpart can be induced by the administration of doxycycline. Major techniques used in Dr. Bok’s research include electron microscopy, laser confocal microscopy, light and electron microscopic autoradiography, cell culture, immunocytochemistry, in situ hybridization cytochemistry, molecular cloning/sequencing and analysis of transgenic animals. Contributions include the discovery of photoreceptor outer segment disc shedding, phagocytosis of these membranes by the RPE, the failure of this process in rat mutants (rdy), detection of membrane receptors for the uptake and release of retinoids by the RPE, transgenic rescue of inherited degeneration in mice carrying the rds mutation and the modeling of the equivalent human disease in mice through the introduction of point mutations in the mouse rds gene.

Publications

A selected list of publications:

Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, Wiita P, Bok D, Sun H.   A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. , Science, ; 315(5813): 820-5.
Radu RA, Yuan Q, Hu J, Peng JH, Lloyd M, Nusinowitz S, Bok D, Travis GH.   Accelerated accumulation of lipofuscin pigments in the RPE of a mouse model for ABCA4-mediated retinal dystrophies following Vitamin A supplementation, Invest Ophthalmol Vis. Sci, 2008; 49(9): 3821-9.
Radu RA, Hu J, Peng J, Bok D, Mata NL, Travis GH.   Retinal pigment epithelium-retinal G protein receptor-opsin mediates light-dependent translocation of all-trans-retinyl esters for synthesis of visual chromophore in retinal pigment epithelial cells, J Biol Chem, 2008; 283(28): 19730-8.
Brill E, Malanson KM, Radu RA, Boukharov NV, Wang Z, Chung HY, Lloyd MB, Bok D, Travis GH, Obin M, Lem J   A novel form of transducin-dependent retinal degeneration: accelerated retinal degeneration in the absence of rod transducin, Invest Ophthalmol Vis. Sci, 2007; 48(12): 5445-53.
Bok D.   Contributions of genetics to our understanding of inherited monogenic retinal diseases and age-related macular degeneration, Arch Oppthalmol, 2007; 125(2): 160-4.
Rhee KD, Ruiz A, Duncan JL, Hauswirth WW, Lavail MM, Bok D, Yang XJ.   Molecular and cellular alterations induced by sustained expression of ciliary neurotrophic factor in a mouse model of retinitis pigmentosa, Invest Ophthalmol Vis. Sci, 2007; 48(3): 1389-400.
Mukherjee PK, Marcheselli VL, Barreiro S, Hu J, Bok D, Bazan NG.   Neurotrophins enhance retinal pigment epithelial cell survival though neuroprotectin D1 signaling, Proc Natl Acad Sci U S A, 2007; 104(32): 13152-7.
Mukherjee PK, Marcheselli VL, Barreiro S, Hu J, Bok D, Bazan NG.   Neurotrophins enhance retinal pigment epithelial cell survival through neuroprotectin D1 signaling, Proc Natl Acad Sci U S A, 2007; 104(32): 13152-7.
Ruiz A, Ghyselinck NB, Mata N, Nusinowitz S, Lloyd M, Dennefeld C, Chambon P, Bok D.   Somatic ablation of the Lrat gene in the mouse retinal pgiment epithelium drastically reduces its retinoid storage, Invest Ophthalmol Vis. Sci, 2007; 48(12): 5377-87.
Senanayake P, Calabro A, Hu JG, Bonilha VL, Darr A, Bok D, Hollyfield JG.   Glucose utilization by the retinal pgment epithelium: evidence for rapid uptake and storage in glycogen, followed by glycogen utilization, Exp Eye Res, 2006; 83(2): 235-46.
Sheren-Manoff M, Shin SJ, Su D, Bok D, Rando RR, Gudas LJ.   Reduced lecithin: retinol acyltransferase expression in human breast cancer, Int J Oncol, 2006; 29(5): 1193-9.
Mora RC, Bonilha VL, Shin BC, Hu J, Cohen-Gould L, Bok D, Rodriguez-Boulan E.   Bipolar assembly of caveolae in retinal pigment epithelium, Am J Physiol Cell Physiol, 2005; 290(3): C832-43.
Bok D.   Cellular mechanisms of retinal degenerations: RPE65, ABCA4, RDS, and bicarbonate transporter genes are examples, Retina, 2005; 25(8): S18-S20.
Bok D.   Ciliary neurotrophic factor therapy for inherited retinal diseases: pros and cons, Retina, 2005; 25(8): S27-S28.
Bok D.   Evidence for an inflammatory process in age-related macular degeneration gains new support, Proc Natl Acad Sci U S A, 2005; 102(20): 7053-4.
Deora AA, Philp N, Hu J, Bok D, Rodriguez-Boulan E.   Mechanisms regulating tissue-specific polarity of monocarboxylate transporters and their chaperone CD147 in kidney and retinal epithelia, Proc Natl Acad Sci U S A, 2005; 102(45): 16245-50.
Radu RA, Han Y, Bui TV, Nusinowitz S, Bok D, Lichter J, Widder K, Travis GH, Mata NL.   Reductions in serum vitamin A arrest accumulation of toxic retinal fluorophores: a potential therapy for treatment of lipofuscin-based retinal diseases, Invest Ophthalmol Vis Sci, 2005; 46(12): 4393-401.
Bok D.   Retinal researchers have reasons to be optimistic, Retina, 2005; 25(8): S43.
Bok D.   The role of RPE65 in inherited retinal diseases, Retina, 2005; 25(8): S61-S62.
Lopez IA, Acuna D, Galbraith G, Bok D, Ishiyama A, Liu W, Kurtz I.   Time course of auditory impairment in mice lacking the electroneutral sodium bicarbonate cotransporter NBC3 (slc4a7), Brain Res Dev Brain Res, 2005; 160(1): 63-77.
Rohrer B, Blanco R, Marc RE, Lloyd MB, Bok D, Schneeweis DM, Reichardt LF.   Functionally intact glutamate-mediated signaling in bipolar cells of the TRKB knockout mouse retina, Vis Neurosci, 2004; 21(5): 703-13.
Bok D.   Gene therapy of retinal dystrophies: achievements, challenges and prospects, Novartis Found Symp, 2004; 255: 4-12.
Boorjian S, Tickoo SK, Mongan NP, Yu H, Bok D, Rando RR, Nanus DM, Scherr DS, Gudas LJ.   Reduced lecithin: retinol acyltransferase expression correlates with increased pathologic tumor stage in bladder cancer, Clin Cancer Res, 2004; 10(10): 3429-3.
Deora AA, Gravotta D, Kreitzer G, Hu J, Bok D, Rodriguez-Boulum E.   The basolateral targeting signal of CD147 (EMMPRIN) consists of a single leucine and is not recognized by retinal pigment epithelium, Mol Biol Cell, 2004; 15(9): 4148-65.
Zhan HC, Gudas LJ, Bok D, Rando R, Nanus DM, Tickoo SK.   Differential expression of the enzyme that esterifies retinol, lecithin: retinol acyltransferase, in subtypes of human renal cancer and normal kidney, Clin Cancer Res, 2003; 9(13): 4897-905.
Bok D, Yasumura D, Matthes MT, Ruiz A, Duncan JL, Chappelow AV, Zolutukhin S, Hauswirth W and LaVail MM.   Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation, Exp Eye Res, 2002; 74: 719-735.
Ruiz A, Kuehn MH, Andorf J, Stone E, Hageman GS and Bok D.   Organization of the lecithin retinol acyltransferase gene and mutation screening in various human hereditary retinal degenerations, Invest. Ophthalmol. Vis. Sci, 2001; 42: 31-37.
Mondal, MS, Ruiz A, Bok D and Rando RR   Lecithin retinol acyltransferse contains cysteine residues essential for catalysis, Biochemistry, 2000; 39: 5215-5220.
Ruiz, A Winston, A Lim, YH Gilbert, BA Rando, RR Bok, D   Molecular and biochemical characterization of lecithin retinol acyltransferase The Journal of biological chemistry. , 1999; 274(6): 3834-41.
Kedzierski, W., Bok D. and Travis, G.H.   Non cell-autonomous photoreceptor degeneration in rds mutant mice mosaic for expression of a rescue transgene, J. Neurosci, 1998; 18: 4076-4082.
Kedzierski, W Lloyd, M Birch, DG Bok, D Travis, GH   Generation and analysis of transgenic mice expressing P216L-substituted rds/peripherin in rod photoreceptors Investigative ophthalmology & visual science. , 1997; 38(2): 498-509.
Ruiz A., Bhat S.P. and Bok D.   Expression and synthesis of the Na,K-ATPase b2 subunit in human retinal pigment epithelium, Gene, 1996; 176: 237-242.
Ruiz, A., Bhat, S.P. and Bok, D.   Characterization and quantification of full-length and truncated Na,K-ATPase a1 and b1 transcripts expressed in human retinal pigment epithelium, Gene, 1995; 155: 179-184.
Ong, DE Davis, JT O’Day, WT Bok, D   Synthesis and secretion of retinol-binding protein and transthyretin by cultured retinal pigment epithelium Biochemistry. , 1994; 33(7): 1835-42.
Bosch, E Horwitz, J Bok, D   Phagocytosis of outer segments by retinal pigment epithelium: phagosome-lysosome interaction The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. , 1993; 41(2): 253-63.

Dean Buonomano, Ph.D.

Biography

NEURAL DYNAMICS: THE NEURAL BASIS OF LEARNING AND MEMORY AND TEMPORAL PROCESSING Behavior and cognition are not the product of isolated neurons, but rather emerge from the dynamics of interconnected neurons embedded in complex recurrent networks. Significant progress has been made towards understanding cellular and synaptic properties in isolation, as well as in establishing which areas of the brain are active during specific tasks. However, elucidating how the activity of hundreds of thousands of neurons within local cortical circuits underlie computations remains an elusive and fundamental goal in neuroscience. The primary goal of my laboratory is to understand how functional computations emerge from networks of neurons. One computation we are particularly interested in is how the brain tells time. Temporal processing refers to your ability to distinguish the interval and duration of sensory stimuli, and is a fundamental component of speech and music perception. To answer these questions the main approaches in my laboratory involve: (1) In Vitro Electrophysiology: Using acute and chronic brain slices we study the spatio-temporal dynamics of cortical circuits, as well as the learning rules that allow networks to develop, organize and perform computations ??? that is, to learn. (2) Computer Simulations: Computer models are used to simulate how networks perform computations, as well as test and generate predictions in parallel with our experimental research. (3) Human Psychophysics: We also use human pyschophysical experiments to characterize learning and generalization of temporal tasks, such as interval discrimination.

Publications

A selected list of publications:

Goel Anubhuti, Buonomano Dean V   Timing as an intrinsic property of neural networks: evidence from in vivo and in vitro experiments Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2014; 369(1637): 20120460.
Laje Rodrigo, Buonomano Dean V   Robust timing and motor patterns by taming chaos in recurrent neural networks Nature neuroscience, 2013; 16(7): 925-33.
Buonomano Dean V, Laje Rodrigo   Population clocks: motor timing with neural dynamics Trends in cognitive sciences, 2010; 14(12): 520-7.
Johnson Hope A, Goel Anubhuthi, Buonomano Dean V   Neural dynamics of in vitro cortical networks reflects experienced temporal patterns Nature neuroscience, 2010; 13(8): 917-9.
Liu Jian K, Buonomano Dean V   Embedding multiple trajectories in simulated recurrent neural networks in a self-organizing manner The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009; 29(42): 13172-81.
Buonomano Dean V   Harnessing chaos in recurrent neural networks Neuron, 2009; 63(4): 423-5.
Buonomano Dean V, Bramen Jennifer, Khodadadifar Mahsa   Influence of the interstimulus interval on temporal processing and learning: testing the state-dependent network model Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2009; 364(1525): 1865-73.
Buonomano Dean V, Maass Wolfgang   State-dependent computations: spatiotemporal processing in cortical networks Nature reviews. Neuroscience, 2009; 10(2): 113-25.
Johnson Hope A, Buonomano Dean V   A method for chronic stimulation of cortical organotypic cultures using implanted electrodes Journal of neuroscience methods, 2009; 176(2): 136-43.
van Wassenhove V, Buonomano DV, Shimojo S, Shams L.   Distortions of subjective time perception within and across senses, PLoS ONE, 2008; 3(1): e1437.
Johnson, Hope A. Buonomano, Dean V.   Development and Plasticity of Spontaneous Activity and Up States in Cortical Organotypic Slices J. Neurosci, 2007; 27(22): 5915-5925.
Buonomano, D. V.   The biology of time across different scales Nat Chem Biol, 2007; 3(10): 594-7.
Karmarkar, U. R. Buonomano, D. V.   Timing in the absence of clocks: encoding time in neural network states Neuron, 2007; 53(3): 427-38.
Karmarkar, U. R. Buonomano, D. V.   Different forms of homeostatic plasticity are engaged with distinct temporal profiles, Eur J Neurosci, 2006; 23(6): 1575-84.
Eagleman, D. M. Tse, P. U. Buonomano, D. Janssen, P. Nobre, A. C. Holcombe, A. O.   Time and the brain: how subjective time relates to neural time, J Neurosci, 2005; 25(45): 10369-71.
Dong, H. W. Buonomano, D. V.   A technique for repeated recordings in cortical organotypic slices, J Neurosci Methods, 2005; 146(1): 69-75.
Buonomano, D. V.   A learning rule for the emergence of stable dynamics and timing in recurrent networks, J Neurophysiol, 2005; 94(4): 2275-83.
Marder, C. P. Buonomano, D. V.   Timing and balance of inhibition enhance the effect of long-term potentiation on cell firing, J Neurosci, 2004; 24(40): 8873-84.
Mauk, M. D. Buonomano, D. V.   The Neural Basis of Temporal Processing, Annual Rev. Neuroscience, 2004; 27: 304-340.
Karmarkar, U. R. Buonomano, D. V.   Temporal specificity of perceptual learning in an auditory discrimination task, Learn Mem, 2003; 10(2): 141-7.
Buonomano, D. V.   Timing of Neural Responses in Cortical Organotypic Slices, Proc. Natl. Acad. Sci. USA, 2003; 100: 4897-4902.
Marder, C. P. Buonomano, D. V.   Differential effects of short- and long-term potentiation on cell firing in the CA1 region of the hippocampus, J Neurosci, 2003; 23(1): 112-21.
Karmarkar, U. R. Buonomano, D. V.   A model of spike-timing dependent plasticity: one or two coincidence detectors?, J Neurophysiol, 2002; 88(1): 507-13.
Buonomano, D. V. Karmarkar, U. R.   How do we tell time?, Neuroscientist, 2002; 8(1): 42-51.
Karmarkar, U. R. Najarian, M. T. Buonomano, D. V.   Mechanisms and significance of spike-timing dependent plasticity, Biol Cybern, 2002; 87(5-6): 373-82.
Buonomano, D. V.   Decoding temporal information: a model based on short-term synaptic plasticity, J Neurosci, 2000; 20: 1129-1141.
Buonomano, D. V.   Distinct functional types of associative long-term potentiation in neocortical and hippocampal pyramidal neurons, J Neurosci, 1999; 19: 6748-6754.
Buonomano, D. V. Merzenich, M.   A neural network model of temporal code generation and position-invariant pattern recognition, Neural Comput, 1999; 11(1): 103-16.
Buonomano, D. V. Merzenich, M. M.   Cortical plasticity: from synapses to maps, Annual Rev. Neuroscience, 1998; 21: 149-186.
Buonomano, D. V. Merzenich, M. M.   Temporal information transformed into a spatial code by a neural network with realistic properties, Science, 1995; 267: 1028-30.
Buonomano, D. V. Byrne, J. H.   Long-term synaptic changes produced by a cellular analog of classical conditioning in Aplysia, Science, 1990; 249(4967): 420-3.