I graduated with a PhD in Pharmacology from University College London in 1986 and then studied with Richard W Tsien as a postdoctoral associate at Yale University School of Medicine and subsequently at Stanford University Medical School. In 1992 I joined the Department of Neuroscience at Brown. I study the expression, regulation, and function of voltage-gated calcium ion channels in different regions of the nervous system. I am also interested in their role in chronic pain and psychiatric disorders. I work closely with undergraduate and graduate students, as well as postdoctoral trainees. I direct the Brown Institute for Brain Science and Direct NIH funded Predoctoral Training Programs in Neuroscience.
|Allen SE, Toro CP, Andrade A, López-Soto EJ, Denome S, Lipscombe D Cell-Specific RNA Binding Protein Rbfox2 Regulates Ca<sub>V</sub>2.2 mRNA Exon Composition and Ca<sub>V</sub>2.2 Current Size.. eNeuro. 2017; 4 (5)|
|O'Hern, Patrick J, do Carmo G. Gonçalves, Inês, Brecht, Johanna, López Soto, Eduardo Javier, Simon, Jonah, Chapkis, Natalie, Lipscombe, Diane, Kye, Min Jeong, Hart, Anne C Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models. eLife/eLife. 2017; 6|
|Tong, Xia-Jing, López-Soto, Eduardo Javier, Li, Lei, Liu, Haowen, Nedelcu, Daniel, Lipscombe, Diane, Hu, Zhitao, Kaplan, Joshua M. Retrograde Synaptic Inhibition Is Mediated by α-Neurexin Binding to the α2δ Subunits of N-Type Calcium Channels. Neuron/Neuron. 2017; 95 (2) : 326-340.e5.|
|Groen JL, Andrade A, Ritz K, Jalalzadeh H, Haagmans M, Bradley TE, Jongejan A, Verbeek DS, Nürnberg P, Denome S, Hennekam RC, Lipscombe D, Baas F, Tijssen MA CACNA1B mutation is linked to unique myoclonus-dystonia syndrome.. Human molecular genetics. 2015; 24 (4) : 987-93.|
|Lipscombe, Diane, Pan, Jen Q., Schorge, Stephanie Tracks through the genome to physiological events. Exp Physiol. 2015; 100 (12) : 1429-1440.|
|Lipscombe D, Pan JQ, Schorge S Tracks through the genome to physiological events.. Exp Physiol. 2015; 100 (12) : 1429-40.|
|Lipscombe D, Andrade A, Allen SE Alternative splicing: functional diversity among voltage-gated calcium channels and behavioral consequences.. Biochimica et biophysica acta. 2013; 1828 (7) : 1522-9.|
|Lipscombe D, Allen SE, Toro CP Control of neuronal voltage-gated calcium ion channels from RNA to protein.. Trends in Neurosciences. 2013; 36 (10) : 598-609.|
|Jiang YQ, Andrade A, Lipscombe D Spinal morphine but not ziconotide or gabapentin analgesia is affected by alternative splicing of voltage-gated calcium channel CaV2.2 pre-mRNA.. Molecular pain. 2013; 9 : 67.|
|Marangoudakis S, Andrade A, Helton TD, Denome S, Castiglioni AJ, Lipscombe D Differential ubiquitination and proteasome regulation of Ca(V)2.2 N-type channel splice isoforms.. Journal of Neuroscience. 2012; 32 (30) : 10365-9.|
|Andrade A, Denome S, Jiang YQ, Marangoudakis S, Lipscombe D Opioid inhibition of N-type Ca2+ channels and spinal analgesia couple to alternative splicing.. Nature Neuroscience. 2010; 13 (10) : 1249-56.|
|Allen SE, Darnell RB, Lipscombe D The neuronal splicing factor Nova controls alternative splicing in N-type and P-type CaV2 calcium channels.. Channels. 2010; 4 (6) : 483-9.|
|Lipscombe, D., Andrade, A., Denome, S., Jiang, Y.-Q., Marangoudakis, S. S17 Ion channels, neuromodulators and ganglionic regulation. Autonomic Neuroscience. 2009; 149 (1-2) : 54.|
|Andrade A, Sandoval A, González-Ramírez R, Lipscombe D, Campbell KP, Felix R The alpha(2)delta subunit augments functional expression and modifies the pharmacology of Ca(V)1.3 L-type channels.. Cell calcium. 2009; 46 (4) : 282-92.|
|Jakubek LM, Marangoudakis S, Raingo J, Liu X, Lipscombe D, Hurt RH The inhibition of neuronal calcium ion channels by trace levels of yttrium released from carbon nanotubes.. Biomaterials. 2009; 30 (31) : 6351-7.|
|Lipscombe D, Pan JQ Tripping the HCN breaker.. Neuron. 2009; 62 (6) : 747-50.|
|Fairbrother WG, Lipscombe D Repressing the neuron within.. BioEssays : news and reviews in molecular, cellular and developmental biology. 2008; 30 (1) : 1-4.|
|Raingo J, Castiglioni AJ, Lipscombe D Alternative splicing controls G protein-dependent inhibition of N-type calcium channels in nociceptors.. Nature Neuroscience. 2007; 10 (3) : 285-92.|
|Lipscombe, Diane, Raingo, Jesica Alternative Splicing Matters: N-Type Calcium Channels in Nociceptors. Channels. 2007; 1 (4) : 225-227.|
|Lipscombe D, Raingo J Alternative splicing matters: N-type calcium channels in nociceptors.. Channels. 2007; 1 (4) : 225-7.|
|Altier C, Dale CS, Kisilevsky AE, Chapman K, Castiglioni AJ, Matthews EA, Evans RM, Dickenson AH, Lipscombe D, Vergnolle N, Zamponi GW Differential role of N-type calcium channel splice isoforms in pain.. Journal of Neuroscience. 2007; 27 (24) : 6363-73.|
|Gray AC, Raingo J, Lipscombe D Neuronal calcium channels: splicing for optimal performance.. Cell calcium. 2007; 42 (4-5) : 409-17.|
|Richards KS, Swensen AM, Lipscombe D, Bommert K Novel CaV2.1 clone replicates many properties of Purkinje cell CaV2.1 current.. European Journal of Neuroscience. 2007; 26 (10) : 2950-61.|
|Castiglioni AJ, Raingo J, Lipscombe D Alternative splicing in the C-terminus of CaV2.2 controls expression and gating of N-type calcium channels.. The Journal of Physiology. 2006; 576 (Pt 1) : 119-34.|
|Lipscombe D, Raingo J Internalizing channels: a mechanism to control pain?. Nature Neuroscience. 2006; 9 (1) : 8-10.|
|Wyllie DJ, Johnston AR, Lipscombe D, Chen PE Single-channel analysis of a point mutation of a conserved serine residue in the S2 ligand-binding domain of the NR2A NMDA receptor subunit.. The Journal of Physiology. 2006; 574 (Pt 2) : 477-89.|
|Helton TD, Xu W, Lipscombe D Neuronal L-type calcium channels open quickly and are inhibited slowly.. Journal of Neuroscience. 2005; 25 (44) : 10247-51.|
|Lipscombe D Neuronal proteins custom designed by alternative splicing.. Current opinion in neurobiology. 2005; 15 (3) : 358-63.|
|Lin Y, McDonough SI, Lipscombe D Alternative splicing in the voltage-sensing region of N-Type CaV2.2 channels modulates channel kinetics.. Journal of Neurophysiology. 2004; 92 (5) : 2820-30.|
|Bell TJ, Thaler C, Castiglioni AJ, Helton TD, Lipscombe D Cell-specific alternative splicing increases calcium channel current density in the pain pathway.. Neuron. 2004; 41 (1) : 127-38.|
|Thaler C, Gray AC, Lipscombe D Cumulative inactivation of N-type CaV2.2 calcium channels modified by alternative splicing.. Proceedings of the National Academy of Sciences. 2004; 101 (15) : 5675-9.|
|Lipscombe D, Helton TD, Xu W L-type calcium channels: the low down.. Journal of Neurophysiology. 2004; 92 (5) : 2633-41.|
|Lipscombe D, Pan JQ, Gray AC Functional diversity in neuronal voltage-gated calcium channels by alternative splicing of Ca(v)alpha1.. Molecular neurobiology. 2002; 26 (1) : 21-44.|
|Lipscombe D L-type calcium channels: highs and new lows.. Circulation research. 2002; 90 (9) : 933-5.|
|Xu W, Lipscombe D Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines.. Journal of Neuroscience. 2001; 21 (16) : 5944-51.|
|Pan JQ, Lipscombe D Alternative splicing in the cytoplasmic II-III loop of the N-type Ca channel alpha 1B subunit: functional differences are beta subunit-specific.. Journal of Neuroscience. 2000; 20 (13) : 4769-75.|
|Lin Z, Lin Y, Schorge S, Pan JQ, Beierlein M, Lipscombe D Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons.. Journal of Neuroscience. 1999; 19 (13) : 5322-31.|
|Schorge S, Gupta S, Lin Z, McEnery MW, Lipscombe D Calcium channel activation stabilizes a neuronal calcium channel mRNA.. Nature Neuroscience. 1999; 2 (9) : 785-90.|
|Lin Z, Haus S, Edgerton J, Lipscombe D Identification of functionally distinct isoforms of the N-type Ca2+ channel in rat sympathetic ganglia and brain.. Neuron. 1997; 18 (1) : 153-66.|
|Lin Z, Harris C, Lipscombe D The molecular identity of Ca channel alpha 1-subunits expressed in rat sympathetic neurons.. Journal of molecular neuroscience : MN. 1996; 7 (4) : 257-67.|
|Tsien RW, Lipscombe D, Madison D, Bley K, Fox A Reflections on Ca(2+)-channel diversity, 1988-1994.. Trends in Neurosciences. 1995; 18 (2) : 52-4.|
|Delcour AH, Lipscombe D, Tsien RW Multiple modes of N-type calcium channel activity distinguished by differences in gating kinetics.. Journal of Neuroscience. 1993; 13 (1) : 181-94.|
|Lipscombe D, Kongsamut S, Tsien RW Alpha-adrenergic inhibition of sympathetic neurotransmitter release mediated by modulation of N-type calcium-channel gating.. J. Geophys. Res.. 1989; 340 (6235) : 639-42.|
|Kongsamut S, Lipscombe D, Tsien RW The N-type Ca channel in frog sympathetic neurons and its role in alpha-adrenergic modulation of transmitter release.. Annals of the New York Academy of Sciences. 1989; 560 : 312-33.|
|Lipscombe D, Madison DV, Poenie M, Reuter H, Tsien RW, Tsien RY Imaging of cytosolic Ca2+ transients arising from Ca2+ stores and Ca2+ channels in sympathetic neurons.. Neuron. 1988; 1 (5) : 355-65.|
|Tsien RW, Lipscombe D, Madison DV, Bley KR, Fox AP Multiple types of neuronal calcium channels and their selective modulation.. Trends in Neurosciences. 1988; 11 (10) : 431-8.|
|Lipscombe D, Rang HP Nicotinic receptors of frog ganglia resemble pharmacologically those of skeletal muscle.. Journal of Neuroscience. 1988; 8 (9) : 3258-65.|
|Lipscombe D, Madison DV, Poenie M, Reuter H, Tsien RY, Tsien RW Spatial distribution of calcium channels and cytosolic calcium transients in growth cones and cell bodies of sympathetic neurons.. Proceedings of the National Academy of Sciences. 1988; 85 (7) : 2398-402.|
We are interested in the cellular mechanisms used to optimize calcium ion channel function. Calcium ion channels regulate many critical neuronal functions including transmitter release, nerve growth, and synaptic plasticity. Our current research focus is on cell-specific alternative splicing in the mammalian nervous system. We study cellular mechanisms that control calcium channel function in normal as well as in disease states, including chronic pain and mental illness.
Voltage-gated calcium channels, the gatekeepers of excitation-driven calcium entry in all excitable cells, control a diverse array of functions. Alternative splicing expands functional capabilities and contributes greatly to the expansion of the proteome required to support complex brain functions. We study alternative splicing of voltage-gated calcium channels. Our work is relevant to basic mechanisms that control channel function in normal and in disease states, including chronic pain and mental illness
Summer E Allen, Cecilia Toro, Arturo Andrade, Eduardo Javier López-Soto, Sylvia Denome, and Diane Lipscombe (2017). Cell-specific RNA binding protein Rbfox2 regulates CaV2.2 mRNA exon composition and overall CaV2.2 current size. In press eNeuro.
Xia-Jing Tong, Eduardo Javier López-Soto, Lei Li, Haowen Liu, Daniel Nedelcu, Diane Lipscombe, Zhitao Hu, Joshua M. Kaplan, Retrograde Synaptic Inhibition Is Mediated by α-Neurexin Binding to the α2δ Subunits of N-Type Calcium Channels (2017). Neuron, Volume 95, Issue 2, 19 July 2017, Pages 326-340.e5, ISSN 0896-6273, https://doi.org/10.1016/j.neuron.2017.06.018.
O’Hern, PJ, do Carmo, I, Gonçalves, G, Brecht, J, López Soto, EJ, Simon, J, Chapkis, N, Lipscombe, D, Kye, MJ, & Hart, AC. (2017). Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models. eLife. https://doi.org/10.7554/eLife.20752. PMCID:PMC5413352.
Andrade A, Hope J, Allen A, Yorgan V, Lipscombe D, Pan JQ. (2016) A rare schizophrenia risk variant of CACNA1I disrupts CaV3.3 channel activity. Scientific Reports. 19;6:34233. doi: 10.1038/srep34233. PMCID: PMC5069464. https://www.ncbi.nlm.nih.gov/pubmed/?cmd=historysearch&querykey=1
Groen JL, Andrade A, Ritz K, Jalalzadeh H, Haagmans M, Bradley TE, Jongejan A, Verbeek DS, Nurnberg P, Denome S, Hennekam RC, Lipscombe D, Baas F & Tijssen MA (2015). CACNA1B mutation is linked to unique myoclonus-dystonia syndrome. Hum Mol Genet 24, 987–993. http://dx.doi.org/10.1093/hmg/ddu513
Lipscombe D, Pan JQ & Schorge S (2015). Tracks through the Genome to Physiological Events. Exp Physiol. http://dx.doi.org/10.1113/EP085129
Lipscombe D & Andrade A (2015). Calcium Channel CaValpha1 Splice Isoforms - Tissue Specificity and Drug Action. Curr Mol Pharmacol. 26, 21-44. http://dx.doi.org/10.1093/hmg/ddu513
Lipscombe, D & Toro (2014). “Biophysical Properties of Voltage-Gated Ion Channels” in 3rd edition “From Molecules to Networks” Eds Jack Byrnes, Ruth Heidelberg, Neal Waxman. Elsevier/Academic Press.
Jiang, Y-Q, Andrade, A & Lipscombe, D (2013) Spinal morphine but not ziconotide or gabapentin analgesia is affected by alternative splicing of voltage-gated calcium channel CaV2.2 pre-mRNA. Molecular Pain 9:67. PMC3916075. http://www.ncbi.nlm.nih.gov/pubmed/24369063?dopt=Citation
Lipscombe, D, Allen, SE, & Toro, CP (2013). Control of neuronal voltage-gated calcium ion channels from RNA to protein. Trends in Neuroscience 36: 598-609. PMID: 23907011. PMCID: PMC3795946.
Lipscombe, D & Toro, CP (nee Phillips, CG) (2013). “Ion Channels”. Encyclopedia of Life Sciences. Nature/Macmillan Press.
Lipscombe, D., Andrade, A., and Allen, S. E. (2013). Alternative splicing: functional diversity among voltage-gated calcium channels and behavioral consequences. Biochem Biophys Acta 1828, 1522-1529. PMCID: PMC3625486.
Manarangoudakis, S, Andrade, A, Helton, TD, Denome, S & Lipscombe, D (2012) Differential Ubiquitination and Proteasomal Regulation of CaV2.2 Splice Isoforms. Journal of Neuroscience 32: 10365-10369. PMCID: PMC3428229
Lipscombe, D. (2011), "Alternative splicing and calcium ion channel diversity", in Levitan, I. (ed.), Ion Channels: , The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/?t=BL1232814-Lipscombe)
Andrade, A, Denome, S, Jiang, Y-Q, Marangoudakis, S & Lipscombe, D (2010). Opioid inhibition of N-type calcium channels and spinal analgesia coupled to alternative splicing. Nature Neuroscience 13:1249-1258.
Allen, SE, Darnell, RB & Lipscombe, D (2010). The neuronal splicing factor Nova controls alternative splicing in N-type and P-type CaV2 calcium channels. Channels 4:483-489.
Andrade, A, Sandoval, A, Lipscombe, D, Campbell, KP & Felix, R (2009). The CaVa2δ subunit augments expression and modifies the pharmacology of CaV1.3 L-type channels. Cell Calcium, 46, 282-292.
Jakubek, L, Marangoudakis, S, Raingo, J, Liu, X, Lipscombe, D & Hurt, R (2009) Neuronal calcium ion channels are inhibited by trace yttrium released from carbon nanotubes. Biomaterials 30: 6351-6357.
Lipscombe, D & Pan, JQ (2009). Tripping the HCN breaker. Neuron 62:747-750.
Fairbrother, W & Lipscombe, D (2008). Repressing the neuron within. Bioessays 30:1-4
Lipscombe, D, Allen, S, Marangoudakis, S, & Raingo, J. (2008) “Alternative splicing of neuronal CaV2 calcium channels” For “Ion channels” Eds Lenard Kaczmarek and Valentin K. Gribkoff. Wiley Publishers
Raingo J, Castiglioni AJ, Lipscombe D. (2007) Alternative splicing controls G protein-dependent inhibition of N-type calcium channels in nociceptors. Nat Neurosci, 10, 285-92.
Altier C, Dale CS, Kisilevsky AE, Chapman K, Castiglioni AJ, Matthews EA, Evans RM, Dickenson AH, Lipscombe D, Vergnolle N, Zamponi GW. (2007) Differential role of N-type calcium channel splice isoforms in pain. J Neurosci, 27, 6363-73.
Gray AC, Raingo J, Lipscombe D. (2007) Neuronal calcium channels: Splicing for optimal performance. Cell Calcium 42:409-417.
Lipscombe, D & Raingo, J (2007). Alternative Splicing Matters: N-type Calcium Channels in Nociceptors. Channels 1:225-227.
Castiglioni, AJ, Raingo, J & Lipscombe, D. (2006). Alternative splicing in the C-terminus of CaV2.2 controls surface expression and gating of N-type calcium channels. Revision in submission. Journal of Physiology. 576:119-134.
Wyllie, DJA, Johnston, AR, Lipscombe, D & Chen, PE. (2006) Single-channel analysis of a point mutation of a conserved serine residue in the S2 ligand binding domain of the NR2A NMDA receptor subunit. Journal of Physiology.574:477-489.
Lipscombe, D & Raingo, J (2006) Internalizing channels: a mechanism to control pain?” Nature Neuroscience 9:8-10.
Helton, TD, Xu, W, & Lipscombe, D (2005). Neuronal L-type calcium channels open quickly and are blocked slowly. J. Neuroscience 25: 10247-10251.
Lipscombe, D. (2005) “Ion channels”. The Encyclopedia of Life Sciences. Macmillan Press.
Lipscombe, D (2005). Neuronal proteins custom designed by alternative splicing. Current Opinions in Neuroscience 15:358-363.
Bell TJ, Thaler C, Castiglioni AJ, Helton, TD and Lipscombe D. (2004). Cell-specific alternative splicing increases calcium channel current density in the pain pathway. Neuron 41: 127-138.
2017-2022 "NeuroNex Technology Hub: Bioluminescence for Optimal Brain Control and Imaging"
PI: Christopher Moore, Co-PI: Diane Lipscombe
Type: Cooperative Agreement
2014-2019 "N-type calcium channel in nociceptive neurons"
PI: Diane Lipscombe
Agency: NIH NINDS
Type: R01 NS055251
2015-2018 "Accelerating identification of cross-species suppressor genes and early identification of pathophysiology in ALS"
PI: Diane Lipscombe; Co-PIs: Anne Hart, Justin Fallon, Kristi Wharton, Robert Reenan, Robert Brown (UMass), Brian Wainger (MGH)
Agency: ALS Finding a Cure Foundation
Type: Research award
Period: 11/01/2015 - 10/30/2018
2015-2018 "Bioluminescent Optogenetics to Autoregulate Excitable Cells"
PI: Christopher Moore; Co-PIs Diane Lipscombe, Julie Kauer, Barry Connors, Ute Hochgeschwender (CMU)
Agency: NIH NINDS
Type: Research Award
Period: 07/01/2015 - 06/30/2018
2016-2021 "Predoctoral Training Program in Neuroscience"
PI: Diane Lipscombe, PI: David Sheinberg
Type: T32MH020068 (Years 17-22)
2014-2019 "Neural Dynamics Predoctoral Training Program in Neuroscience"
PI: Diane Lipscombe; PI: Christopher Moore
|Connors, Barry||L. Herbert Ballou University Professor of Neuroscience, Professor of Medical Science|
|Fallon, Justin||Professor of Medical Science, Professor of Psychiatry and Human Behavior|
|Kauer, Julie||Professor of Medical Science, Professor of Neuroscience|
|Moore, Christopher||Professor of Neuroscience|
|Reenan, Robert||Professor of Biology|
|Wharton, Kristi||Professor of Biology|
Director, Brown Institute for Brain Science
Board of Directors, Care New England Heath Care System, RI
Member of Council Society for Neuroscience
Member at large Neuroscience Section for AAAS
I was honored to receive the 2008 Harriet W. Sheridan Award for Distinguished Contribution to Teaching and Learning at Brown, the 2010 Faculty Mentorship Award from the Graduate School, and the 2013 Dean's award for excellence in Graduate and or Postdoctoral Teaching and Mentoring in the Biological Sciences.
I teach the 1st year core graduate course BN203 "Advanced Cellular and Molecular Neurobiology" and have served as Independent Study advisor for many undergraduate students.
I co-organize a graduate level "Bench to Bedside" course and help coordinate workshops for the graduate students.
|NEUR 2030 - Advanced Molecular and Cellular Neurobiology I|