Biomedical Research Education & Training
Faculty Member

Miller, David M., Ph.D.
Professor of Cell and Developmental Biology
Professor of Biological Science

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Phone Number: (615) 343-3447

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Miller, David's picture
Academic history
B.S., University of Southern Mississippi, Hattiesburg, MS
Ph.D., Rice University, Houston, TX

Office Address   Mailing Address

3120 MRB III

3120A MRB III Cell and Developmental Biology 8240

Research Keywords
Molecular Neurobiology | Neural Specificity | C. elegans synaptic plasticity dendrite morphogenesis neuron degeneration and regeneration,C. elegans,Developmental biology,Gene regulation,Genetics,Genome,Genomics,Mutation,Neuroscience,Receptor,Signal transduction,Transcription factor

Research Specialty
development of the nervous system

Research Description
The human brain embodies the most complex and functionally remarkable tissue in biology. These attributes are defined by elaborate, highly connected networks in which myriad types of neurons are linked together in circuits with discrete physiological roles. I am interested in fundamental mechanisms that drive the creation and maintenance of this intricate structure. To obviate the need to study the brain directly, we are using the model organism, C. elegans, to reveal the underlying programs that specify neural architecture. With its simple, well-defined nervous system and facile genetics, C. elegans, is especially well-suited to this approach. For example, the phenomenon of synaptic specificity is readily evident in the wiring diagram of the C. elegans nervous system which catalogs synaptic partners for all 302 neurons in the circuit. We have exploited this resource to identify genetic mutants that alter connectivity and thus define pathways that are normally required for directing the creation of synapses between specific neurons. The execution of these developmental programs depends on expression of unique combinations of genes in different types of neurons. With the goal of identifying these genetic signatures, the Miller lab has pioneered the development of robust methods for generating neuron-specific gene expression profiles. Reverse genetic strategies (e.g., RNAi) are then employed to test candidate genes from these lists for key roles in circuit architecture. Perturbations are readily detected in this small, transparent organism with high-resolution light microscopy of neurons and synapses marked with fluorescent proteins (e.g., GFP). In addition to uncovering mechanisms that direct synaptic specificity, the Miller lab has also used these methods to address other fundamental processes in neural development including synaptic plasticity, dendrite morphogenesis and nerve regeneration. These studies are expected to reveal genetic networks with similar roles in human brain development and thus can lead to a deeper understanding of mechanisms that protect the brain from disease and repair damage arising from injury.

Gerstein, MB, Rozowsky, J, Yan, KK, Wang, D, Cheng, C, Brown, JB, Davis, CA, Hillier, L, Sisu, C, Li, JJ, Pei, B, Harmanci, AO, Duff, MO, Djebali, S, Alexander, RP, Alver, BH, Auerbach, R, Bell, K, Bickel, PJ, Boeck, ME, Boley, NP, Booth, BW, Cherbas, L, Cherbas, P, Di, C, Dobin, A, Drenkow, J, Ewing, B, Fang, G, Fastuca, M, Feingold, EA, Frankish, A, Gao, G, Good, PJ, Guig??, R, Hammonds, A, Harrow, J, Hoskins, RA, Howald, C, Hu, L, Huang, H, Hubbard, TJ, Huynh, C, Jha, S, Kasper, D, Kato, M, Kaufman, TC, Kitchen, RR, Ladewig, E, Lagarde, J, Lai, E, Leng, J, Lu, Z, MacCoss, M, May, G, McWhirter, R, Merrihew, G, Miller, DM, Mortazavi, A, Murad, R, Oliver, B, Olson, S, Park, PJ, Pazin, MJ, Perrimon, N, Pervouchine, D, Reinke, V, Reymond, A, Robinson, G, Samsonova, A, Saunders, GI, Schlesinger, F, Sethi, A, Slack, FJ, Spencer, WC, Stoiber, MH, Strasbourger, P, Tanzer, A, Thompson, OA, Wan, KH, Wang, G, Wang, H, Watkins, KL, Wen, J, Wen, K, Xue, C, Yang, L, Yip, K, Zaleski, C, Zhang, Y, Zheng, H, Brenner, SE, Graveley, BR, Celniker, SE, Gingeras, TR, Waterston, R. Comparative analysis of the transcriptome across distant species. Nature, 512(7515), 445-8, 2014

Spencer, WC, McWhirter, R, Miller, T, Strasbourger, P, Thompson, O, Hillier, LW, Waterston, RH, Miller, DM. Isolation of specific neurons from C. elegans larvae for gene expression profiling. PLoS One, 9(11), e112102, 2014

Smith, CJ, O''Brien, T, Chatzigeorgiou, M, Spencer, WC, Feingold-Link, E, Husson, SJ, Hori, S, Mitani, S, Gottschalk, A, Schafer, WR, Miller, DM. Sensory Neuron Fates Are Distinguished by a Transcriptional Switch that Regulates Dendrite Branch Stabilization. Neuron, 79(2), 266-80, 2013

Wang, Y, Matthewman, C, Han, L, Miller, T, Miller, DM, Bianchi, L. Neurotoxic unc-8 mutants encode constitutively active DEG/ENaC channels that are blocked by divalent cations. J Gen Physiol, 142(2), 157-69, 2013

Schneider, J, Skelton, RL, Von Stetina, SE, Middelkoop, TC, van Oudenaarden, A, Korswagen, HC, Miller, DM. UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit. Development, 139(12), 2234-45, 2012

Smith, CJ, Watson, JD, VanHoven, MK, Col??n-Ramos, DA, Miller, DM. Netrin (UNC-6) mediates dendritic self-avoidance. Nat Neurosci, 15(5), 731-7, 2012

Albeg, A, Smith, CJ, Chatzigeorgiou, M, Feitelson, DG, Hall, DH, Schafer, WR, Miller, DM, Treinin, M. C. elegans multi-dendritic sensory neurons: morphology and function. Mol Cell Neurosci, 46(1), 308-17, 2011 PMCID:3006369

Hallem, EA, Spencer, WC, McWhirter, RD, Zeller, G, Henz, SR, R??tsch, G, Miller, DM, Horvitz, HR, Sternberg, PW, Ringstad, N. Receptor-type guanylate cyclase is required for carbon dioxide sensation by Caenorhabditis elegans. Proc Natl Acad Sci U S A, 108(1), 254-9, 2011 PMCID:3017194

Lu, ZJ, Yip, KY, Wang, G, Shou, C, Hillier, LW, Khurana, E, Agarwal, A, Auerbach, R, Rozowsky, J, Cheng, C, Kato, M, Miller, DM, Slack, F, Snyder, M, Waterston, RH, Reinke, V, Gerstein, MB. Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data. Genome Res, 21(2), 276-85, 2011 PMCID:3032931

Petersen, SC, Watson, JD, Richmond, JE, Sarov, M, Walthall, WW, Miller, DM. A transcriptional program promotes remodeling of GABAergic synapses in Caenorhabditis elegans. J Neurosci, 31(43), 15362-75, 2011 PMCID:3229156

Spencer, WC, Zeller, G, Watson, JD, Henz, SR, Watkins, KL, McWhirter, RD, Petersen, S, Sreedharan, VT, Widmer, C, Jo, J, Reinke, V, Petrella, L, Strome, S, Von Stetina, SE, Katz, M, Shaham, S, R??tsch, G, Miller, DM. A spatial and temporal map of C. elegans gene expression. Genome Res, 21(2), 325-41, 2011 PMCID:3032935

Chatzigeorgiou, M, Yoo, S, Watson, JD, Lee, WH, Spencer, WC, Kindt, KS, Hwang, SW, Miller, DM, Treinin, M, Driscoll, M, Schafer, WR. Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegans nociceptors. Nat Neurosci, 13(7), 861-8, 2010

Earls, LR, Hacker, ML, Watson, JD, Miller, DM. Coenzyme Q protects Caenorhabditis elegans GABA neurons from calcium-dependent degeneration. Proc Natl Acad Sci U S A, 107(32), 14460-5, 2010

Hammock, EA, Eagleson, KL, Barlow, S, Earls, LR, Miller, DM, Levitt, P. Homologs of genes expressed in Caenorhabditis elegans GABAergic neurons are also found in the developing mouse forebrain. Neural Dev, 5, 32, 2010 PMCID:3006369

Smith, CJ, Watson, JD, Spencer, WC, O'Brien, T, Cha, B, Albeg, A, Treinin, M, Miller, DM. Time-lapse imaging and cell-specific expression profiling reveal dynamic branching and molecular determinants of a multi-dendritic nociceptor in C. elegans. Dev Biol, 345, 18-33, 2010

Thorne, CA, Hanson, AJ, Schneider, J, Tahinci, E, Orton, D, Cselenyi, CS, Jernigan, KK, Meyers, KC, Hang, BI, Waterson, AG, Kim, K, Melancon, B, Ghidu, VP, Sulikowski, GA, LaFleur, B, Salic, A, Lee, LA, Miller, DM, Lee, E. Small-molecule inhibition of Wnt signaling through activation of casein kinase 1I?. Nat Chem Biol, 6(11), 829-36, 2010 PMCID:3006369

Helmcke, KJ, Syversen, T, Miller, DM, Aschner, M. Characterization of the effects of methylmercury on Caenorhabditis elegans. Toxicol Appl Pharmacol, 240(2), 265-72, 2009

Meissner, B, Warner, A, Wong, K, Dube, N, Lorch, A, McKay, SJ, Khattra, J, Rogalski, T, Somasiri, A, Chaudhry, I, Fox, RM, Miller, DM, Baillie, DL, Holt, RA, Jones, SJ, Marra, MA, Moerman, DG. An integrated strategy to study muscle development and myofilament structure in Caenorhabditis elegans. PLoS Genet, 5(6), e1000537, 2009 PMCID:2694363

Watson, JD, Wang, S, Von Stetina, SE, Spencer, WC, Levy, S, Dexheimer, PJ, Kurn, N, Heath, JD, Miller, DM. Complementary RNA amplification methods enhance microarray identification of transcripts expressed in the C. elegans nervous system. BMC Genomics, 9, 84, 2008 PMCID:2263045

Fox, RM, Watson, JD, Von Stetina, SE, McDermott, J, Brodigan, TM, Fukushige, T, Krause, M, Miller, DM. The embryonic muscle transcriptome of Caenorhabditis elegans. Genome Biol, 8(9), R188, 2007 PMCID:2375026

Miller, DM. Neuroscience. Synapses here and not everywhere. Science, 317(5840), 907-8, 2007

Von Stetina, SE, Fox, RM, Watkins, KL, Starich, TA, Shaw, JE, Miller, DM. UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans. Genes Dev, 21(3), 332-46, 2007 PMCID:1785118

Von Stetina, SE, Watson, JD, Fox, RM, Olszewski, KL, Spencer, WC, Roy, PJ, Miller, DM. Cell-specific microarray profiling experiments reveal a comprehensive picture of gene expression in the C. elegans nervous system. Genome Biol, 8(7), R135, 2007 PMCID:2323220

Varadan, V, Miller, DM, Anastassiou, D. Computational inference of the molecular logic for synaptic connectivity in C. elegans. Bioinformatics, 22(14), e497-506, 2006

Fox, RM, Von Stetina, SE, Barlow, SJ, Shaffer, C, Olszewski, KL, Moore, JH, Dupuy, D, Vidal, M, Miller, DM. A gene expression fingerprint of C. elegans embryonic motor neurons. BMC Genomics, 6(1), 42, 2005 PMCID:1079822

Touroutine, DV, Fox, RM, Von Stetina, SE, Burdina, AO, Miller, DM, Richmond, JE. ACR-16 encodes an essential subunit of the levamisole-resistant nicotinic receptor at the C. elegans neuromuscular junction. J Biol Chem, 2005

Von Stetina, SE, Treinin, M, Miller, DM. The motor circuit. Int Rev Neurobiol, 69, 125-67, 2005

Sedensky, M M, Siefker, J M, Koh, J Y, Miller, D M, Morgan, P G. A stomatin and a degenerin interact in lipid rafts of the nervous system of Caenorhabditis elegans. Am J Physiol Cell Physiol, 287(2), C468-74, 2004

Christensen, M, Estevez, A, Yin, X, Fox, R, Morrison, R, McDonnell, M, Gleason, C, Miller, DM, Strange, K. A primary culture system for functional analysis of C. elegans neurons and muscle cells. Neuron, 33(4), 503-14, 2002

Esmaeili, B, Ross, JM, Neades, C, Miller, DM, Ahringer, J. The C. elegans even-skipped homologue, vab-7, specifies DB motoneurone identity and axon trajectory. Development, 129(4), 853-62, 2002

Nass, Richard, Hall, David H, Miller, David M, Blakely, Randy D. Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Proc Natl Acad Sci U S A, 99(5), 3264-9, 2002 PMCID:122507

Bianchi, L, Miller, D M, George, A L. Expression of a CIC chloride channel in Caenorhabditis elegans gamma-aminobutyric acid-ergic neurons. Neurosci Lett, 299(3), 177-80, 2001

Lickteig, K M, Duerr, J S, Frisby, D L, Hall, D H, Rand, J B, Miller, D M. Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4 and its transcriptional corepressor UNC-37/groucho in Caenorhabditis elegans cholinergic motor neurons. J Neurosci, 21(6), 2001-14, 2001

Nass, R, Miller, D, Blakely, R. C. elegans: a novel pharmacogenetic model to study Parkinson's disease. , 7(3), 185-191, 2001

Miller, D M, Desai, N S, Hardin, D C, Piston, D W, Patterson, G H, Fleenor, J, Xu, S, Fire, A. Two-color GFP expression system for C. elegans. Biotechniques, 26(5), 914-8, 920-1, 1999

Winnier, A R, Meir, J Y, Ross, J M, Tavernarakis, N, Driscoll, M, Ishihara, T, Katsura, I, Miller, D M. UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls synaptic choice in Caenorhabditis elegans. Genes Dev, 13(21), 2774-86, 1999 PMCID:317130

Jayanthi, LD, Apparsundaram, S, Malone, MD, Ward, E, Miller, DM, Eppler, M, Blakely, RD. The Caenorhabditis elegans gene T23G5.5 encodes an antidepressant- and cocaine-sensitive dopamine transporter. Mol Pharmacol, 54(4), 601-9, 1998

Pflugrad, A, Meir, J Y, Barnes, T M, Miller, D M. The Groucho-like transcription factor UNC-37 functions with the neural specificity gene unc-4 to govern motor neuron identity in C. elegans. Development, 124(9), 1699-709, 1997

Miller, D M, Niemeyer, C J. Expression of the unc-4 homeoprotein in Caenorhabditis elegans motor neurons specifies presynaptic input. Development, 121(9), 2877-86, 1995

Miller, D M, Shakes, D C. Immunofluorescence microscopy. Methods Cell Biol, 48, 365-94, 1995

Miller, DM, Niemeyer, CJ, Chitkara, P. Dominant unc-37 mutations suppress the movement defect of a homeodomain mutation in unc-4, a neural specificity gene in Caenorhabditis elegans. Genetics, 135(3), 741-53, 1993 PMCID:1205717

Miller, DM, Shen, MM, Shamu, CE, B??rglin, TR, Ruvkun, G, Dubois, ML, Ghee, M, Wilson, L. C. elegans unc-4 gene encodes a homeodomain protein that determines the pattern of synaptic input to specific motor neurons. Nature, 355(6363), 841-5, 1992

Maruyama, IN, Miller, DM, Brenner, S. Myosin heavy chain gene amplification as a suppressor mutation in Caenorhabditis elegans. Mol Gen Genet, 219(1-2), 113-8, 1989

Miller, DM, Stockdale, FE, Karn, J. Immunological identification of the genes encoding the four myosin heavy chain isoforms of Caenorhabditis elegans. Proc Natl Acad Sci U S A, 83(8), 2305-9, 1986 PMCID:323285

Epstein, HF, Miller, DM, Ortiz, I, Berliner, GC. Myosin and paramyosin are organized about a newly identified core structure. J Cell Biol, 100(3), 904-15, 1985 PMCID:2113503

Watts, FZ, Miller, DM, Orr, E. Identification of myosin heavy chain in Saccharomyces cerevisiae. Nature, 316(6023), 83-5, 1985

Miller, DM, Ortiz, I, Berliner, GC, Epstein, HF. Differential localization of two myosins within nematode thick filaments. Cell, 34(2), 477-90, 1983

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