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Scholarly Interest Report
         
Michael Stern
Professor
Professor of Biochemistry and Cell Biology
 
e-mail:stern@rice.edu
 
  • B.S. Biochemistry (1978) Stanford University, Stanford, California
  • Ph.D. Biochemistry (1985) University of California, San Francisco, San Francisco, California
 
Primary Department
   Department of BioSciences
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Department Affiliations
 
  • Institute of Biosciences and Bioengineering
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    Research Areas
     Neuron-glia interactions within the Drosophila peripheral nerve, regulation of motor neuron excitability, regulation of ecdysone synthesis
     
    Research Statement
     

    Drosophila peripheral nerves, similar structurally to the peripheral nerves of mammals, comprise a central core of motor and sensory axons, surrounded by two layers of glia: an inner glial layer, termed the peripheral glia, and an outer, perineurial glial layer. Although it has been well established that intercellular signalling occurs among these cell types, neither the signalling pathways involved nor the functional effects of these pathways are completely understood. stern_CB_cover002.jpg We are using genetic methodology to address these questions. We have found that intercellular signalling controls at least two aspects of peripheral nerve structure or function. First, intercellular signalling controls growth of the perineurial glial layer. At least seven genes participate in this regulation. These genes include Ras and the Ras-GTPase activating protein encoded by the Drosophila orthologue of the gene responsible for the human genetic disease of Neurofibromatosis. Further studies of this pathway are underway. Second, neuron-glia signalling also affects neuronal excitability via regulation of axonal sodium channels. Loss of function mutations in the inebriated (ine)-encoded neurotransmitter transporter increase sodium currents, whereas overexpression of ine reduces sodium currents. Efforts are currently underway to identify and determine the functions of molecules responsible for this regulation.

     
    Teaching Areas
     advanced genetics, senior honors research
     
    Selected Publications
     Refereed articles
     

    Faust JE, Manisundaram A, Ivanova PT, Milne SB, Summerville JB, Brown HA, Wangler M, Stern M, McNew JA "Peroxisomes are required for lipid metabolism and muscle function in Drosophila melanogaster." PLoS One, 9(6) (2014) : e100213.

     
     

    McNew JA, Sondermann H, Lee T, Stern M, Brandizzi F. "GTP-dependent membrane fusion." Annu Rev Cell Dev Biol, 29 (2013) : 529-50.

     
     

    Johnson C, Chun-Jen Lin C, Stern M. "Ras-dependent and Ras-independent effects of PI3K in Drosophila motor neurons.." Genes, Brain and Behavior, 11 (2012) : 848-858.

     
     

    Lin, C.-J., Summerville, J.B., Howlett, E., and Stern, M "The metabotropic glutamate receptor activates the lipid kinase PI3K in Drosophila motor neurons through the calcium/calmodulin-dependent protein kinase II and the nonreceptor tyrosine protein kinase DFak." Genetics, 188 (2011) : 601-613.

     
     

    Stern, M. "Insulin signaling and autism." Front. Endocrin., 2 (2011) : 54.

     
     

    Huang, Y., Howlett, E., Stern, M., and Jackson, F.R. "Altered LARK expression perturbs development and physiology of the Drosophila PDF clock neurons." Mol. Cell. Neurosci., 41 (2009) : 196-205.In Press

     
     

    Walkiewicz, M., and Stern, M. "Increased insulin/insulin growth factor signalling advances the onset of metamorphosis in Drosophila." PLoS One, 4 (2009) : e5072.In Press

     
     

    Howlett, E., Lin, C.C., Lavery, W., and Stern, M. "A Pl3-kinase-mediated negative feedback regulates neuronal excitability." PLoS Genet., 4(11) (2008) : e1000277.

     
     

    Lavery, W., Hall, V., Yager, J., Rottgers, S., Wells, M., and Stern, M. "Phosphatidyl inositol-3-kinase and Akt nonautonomously promote perineurial glial growth in Drosophila peripheral nerves." J. Neurosci., 27 (2007) : 279-288.

     
     

    Cardnell, R.J.G., Dalle Nogare, D., Ganetzky, B. and Stern, M. "In vivo analysis of a gain-of-function mutation in the Drosophila eag-encoded K channel." Genetics, 172 (2006) : 2351-2358.

     
     

    Caldwell, P.E., Walkiewicz, M., and Stern, M. "Ras activity in the Drosophila prothoracic gland regulates body size and developmental rate via ecdysone release." Current Biology, 15 (2005) : 1785-1795.

     
     

    Huang, X., Huang, Y., Chinnappan, R., Bocchini, C., Gustin, M.C., and Stern, M. "The Drosophila inebriated-Encoded Neurotransmitter/Osmolyte Transporter: Dual Roles in the Control of Neuronal Excitability and the Osmotic Stress Response." Genetics, 160 (2002) : 561-569.

     
     

    Huang, Y., and Stern, M. "In vivo Properties of the Drosophila inebriated-Encoded Neurotransmitter Transporter." J. Neurosci., 22 (2002) : 1698-1708.

     
     

    Schweers, B.A., Walters, K.J., and Stern, M. "The Drosophila melanogaster translational regulator pumilio regulates neuronal excitability." Genetics, 161 (2002) : 1175-1185.

     
     

    Yager, J., Richards, S., Hekmat-Scafe, D., Hurd, D., Sunderesan, V., Caprette, D., Saxton, W., Carlson, J., and Stern, M. "Control of Drosophila Perineural Glial Growth by Two Interacting Neurotransmitter-mediated Signaling Pathways." Proc. Natl. Acad. Sci., 98 (2001) : 10445-10450.

     
     

    Arredondo, L., Nelson, H.B., Beckingham, K., and Stern, M. "Increased Transmitter Release and Aberrant Synaptic Morphology in Drosophila calmodulin Mutants." Genetics, 150 (1998) : 265-274.

     
     

    Nelson, H.B., Heiman, R.G., Bolduc, C., Kovalick, G.E., Whitley, P., Stern, M., and Beckingham, K. "Calmodulin Point Mutations Affect Drosophila Development and Behavior." Genetics, 147 (1997) : 1783-1798.

     
     

    Soehnge, H., Huang, X., Becker, M., Conover, D., and Stern, M. "Cloning and Sequencing of Ribosomal Protein L27a and a Gene Similar to Human GS1 in Drosophila." Gene, 185 (1997) : 257-263.

     
     

    Hurd, D.D., Stern, M., and Saxton, W.M. "Mutation of the Axonal Transport Motor Kinesin Enhances paralytic and Suppresses shaker." Genetics, 142 (1996) : 195-204.

     
     

    Richards, S., Hillman, T., and Stern, M. "Mutations in the Drosophila pushover Gene Confer Increased Neuronal Excitability and Spontaneous Synaptic Vesicle Fusions." Genetics, 142 (1996) : 1215-1223.

     
     

    Soehnge, H., Huang, X., Becker, M., Whitley, P., Conover, D., and Stern, M. "A Neurotransmitter Transporter Encoded by the Drosophila inebriated Gene." Proc. Natl. Acad. Sci. USA, 93 (1996) : 13262-13267.

     
     

    Warbington, L., Hillman, T., Adams, C., and Stern, M. "Reduced Transmitter Release Conferred by Mutations in the slowpoke-Encoded Ca2+-activated K+ Channel Gene of Drosophila." Invertebrate Neuroscience, 2 (1996) : 51-60.

     
     

    Stern, M., Blake, N., Zondlo, N., and Walters, K. "Increased Neuronal Excitability Conferred by a Mutation in the Drosophila bemused Gene." J. Neurogen., 10 (1995) : 103-118.

     
    Presentations
     Invited Talks
     

    "PI3K regulate growth within the prothoracic gland via GSK3 and cyclin D/CDK4." Ecdysone Workshop 2010, Ceske Buejovice, Czech Republic. (July 2010)

     
     

    speaker.  "Insulin released from Drosophila insulin-producing cells is sufficient to accelerate larval development." Molecular Mechanisms of Developmental Timing, Janelia Farm Research Campus, Virginia. (May 4, 2008-May 7, 2008) With Magdalena Walkiewicz

     
     

    "Evidence that PI3 kinase mediates the effects of Ras on perineurial glial growth in Drosophila." Molecular Biology of NF1 and NF2, (May 23-25, 2004)

     
     

    "Intercellular signalling within the Drosophila peripheral nerve." Department of Neurobiology, University of Texas, Austin, Texas. (March 21, 2004)

     
     

    "Neuropeptide-mediated Growth Control." Molecular Neurobiology of Drosophila, Cold Spring Harbor, New York. (October 1-5, 2003)

     
     

    "Ras Activity in Peripheral Glia Promotes Perineurial Glial Growth in Drosophila Peripheral Nerves." Molecular Biology of NF1 and NF2, Aspen, Colorado. (June 1-4, 2003)

     
     

    "Ras activation is both necessary and sufficient to promote perineurial glial growth in Drosophila peripheral nerves." American Society for Neurochemistry 33rd Annual Meeting, West Palm Beach, Florida. (June 22-26, 2002)

     
     Other
     

    "P13-Kinase regulates neuronal excitability and axonal growth and arborization via distinct effector pathways." 48th Annual Drosophila Conference, Philadelphia. (March 7-11, 2007) With E. Howlett

     
     

    "Intercellular Signalling within the Drosophila Segmental Nerve." Department of Molecular Genetics, Baylor College of Medicine, Houston, Texas. (April 2000)

     
     

    "Intercellular Signalling within the Drosophila Segmental Nerve." Department of Biochemistry, Baylor College of Medicine, Houston, Texas. (November 2000)

     
     Posters
     

    Graduate Research Advisor.  "Ral, but not Raf, enhances the nonautonomous effects of PI3K on perineurial glial growth in the fly peripheral nerve." Children's Tumor Foundation Neurofibromatosis Conference, (June 10-12, 2007) With W. Lavery

     
     

    lab director.  "Ras, Raf and P13-Kinase activities in peripheral glia regulate perinuerial glial cell number in larval peripheral nerves." 48th Annual Drosophila Research Conference, Philadelphia. (March 7-11, 2007) With W. Lavery

     
     

    "In vivo Analysis of ether-a-go-go Gain of Function Mutation." 47th Annual Drosophila Research Conference, Houston, Texas. (March 29-April 2, 2006) With R. Cardnell and D. Dalle Nogare

     
     

    "Foxo Mediates the Nonautonomous Effects of Ras and PI3 Kinase in Peripheral Nerve Growth." 47th Annual Drosophila Research Conference, Houston, Texas. (March 29-April 2, 2006) With W. Lavery

     
     

    "Foxo Mediates the Nonautonomous Effects of Ras and PI3 Kinase in Peripheral Nerve Growth." 2006 Children's Tumor Foundation International Neurofibromitosis Consortium, Aspen, Colorado. With W. Lavery

     
     

    "Ras Activity in the Prothoracic Gland Regulates Body Size and Developmental Rate via Acdysone Release." 47th Annual Drosophila Research Conference, Houston, Texas. (March 29-April 2, 2006) With P. Caldwell and M. Walkiewicz

     
     

    "In vivo analysis of ether a go-go gain of function mutations." Neurobiology of Drosophila, Cold Spring Harbor, New York. With R.J.G. Cardnell, D.E. Dalle Nogare and B. Ganetaky

     
     46: 668B
     
    Supervised Theses & Dissertations
     Ph.D. A Description of an Optomotor Reflex Using Methods from Control Theory, Cross-Correlation Analysis, and Information Theory. (2002) (Thesis Committee Member)

     Brett Schweers, Ph.D. The Drosophila melanogaster Gene, bemused, Is a New Allele of pumilio: Insights into Understanding the Role of Translational Regulation in the Maintenance of Proper Neuronal Excitability. (2002) (Thesis Director)

     James Yager, Ph.D. Control of Perineurial Glial Growth inDrosophila melanogaster. (2002) (Thesis Director)

     Han Xu, Ph.D. Repressor Proteins: Ligand Binding, Thermodynamics and Assembly. (2002) (Thesis Committee Member)

     Wonhee Jang, Ph.D. Theoretical and Experimental Studies on a Cell Number Sensing Mechanism. (2003) (Thesis Committee Member)

     Emily Horton, Ph.D. Heterologous Expression of Alcohol Acetyltransferase Genes in Escherichia coli and Clostridium acetobutylicum for the Production of Esters. (2004) (Thesis Committee Member)

     Brenton Scott, Ph.D. Regulation of SNARE-Mediated Membrane Fusion by Sec1/Munc18 (SM) Proteins. (2005) (Thesis Committee Member)

     Jamie Catanese, Ph.D. Biophysical and Biochemical Characterization of the Disconnected Interacting Protein 1, DIP1, from Drosophila melanogaster. (2005) (Thesis Committee Member)

     David Ji, MA Elucidating the Mechanism of Action of Lmo4 in Vertebrate Eye Development. (2005) (Thesis Committee Member)

     Robert Cardnell, Ph.D. In vivo Analysis of Gain-of-function Mutations in the Drosophila eag-Encoded K+ Channel. (2006) (Thesis Director)

     Jamie Becnel, Ph.D. Xyloglucan Endotransglucosylase/Hydrolases of Arabidopsis: Expression and Function of a Gene Family. (2006) (Thesis Committee Member)

     Neda Nikravan, M.A. The Study of an Autocrine Signal Transduction Pathway that Represses Cell Proliferation in Dictyostelium discoideum. (2007) (Thesis Committee Member)

     Philip Caldwell, Ph.D. Ras Signaling in Either Prothoracic Gland Cells or Cholinergic Neurons of Drosophila melanogaster Regulates Fly Size. (2007) (Thesis Director)

     Ying Frances Liu, Ph.D. Exploration of DNA Binding Selectivity, Transcriptional Regulation, and Evolutionary Relationships of the Hox Protein Ultrabithorax. (2007) (Thesis Committee Member)

     Damian Dalle Nogare, Ph.D. Molecular-Genetic Analysis of Cell Cycle Diversification in Early Zebrafish Embryos. (2007) (Thesis Committee Member)

     Jonathan Choe, M.A. AprA: An Autocrine, Secreted Factor that Represses Cell Proliferation in Dictyostelium discoideum. (2008) (Thesis Committee Member)

     Eric Howlett, PhD A P13-kinase mediated negative feedback regulates neuronal excitability at the Drosophila neuromuscular junctio. (2009) (Thesis Director)

     James Summerville, Ph.D. The Effects of ER Morphology on Synaptic Structure and Function in Drosophila melanogaster. (2015) (Thesis Director)

     Yitai Tang, Ph.D. Characterization of CnrN-mediated Size Regulation in Dictyostelium. (2200) (Thesis Committee Member)

     Breanna Ullmann, Ph.D. Identification and Characterization of Yeast Genes Involved in Defense against Oxidative Stress Induced by Macrophages. (Thesis Committee Member)

     Miguel A Betancourt, In vitro structure-function analysis of Drosophila atlastin. (Thesis Committee Member)

    Awards, Prizes, & Fellowships
     Hamill Foundation Award, (2012-2013)

     Member, NIH MDCN4 Study Section,

     Member, Genetics Society of America,

     Member, Ad hoc NIH MDCN5 Study Section, (June 2001)

     Member, Society for Neurosciences,

     Member, Genetics Society of America

     Member, Society for Neurosciences