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 am the Director of the Robery J. & Nancy D. Carney Institute for Brain Science and direct NIH funded Predoctoral Training Programs in Neuroscience.
Diane Lipscombe & Eduardo Javier Lopez Soto
Alternative Splicing of Neuronal Genes: New mechanisms and New Therapies.
Current opinion in neurobiology. 2019;
|Held A, Major P, Sahin A, Reenan R, Lipscombe D, Wharton KA Circuit dysfunction in SOD1-ALS model first detected in sensory feedback prior to motor neuron degeneration is alleviated by BMP signaling.. Journal of Neuroscience. 2019;|
|Yanagi KS, Wu Z, Amaya J, Chapkis N, Duffy AM, Hajdarovic KH, Held A, Mathur AD, Russo K, Ryan VH, Steinert BL, Whitt JP, Fallon JR, Fawzi NL, Lipscombe D, Reenan RA, Wharton KA, Hart AC Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.. Neuroscience. 2019; 396 : A3-A20.|
|Pradier B, Shin HB, Kim DS, St Laurent R, Lipscombe D, Kauer JA Long-Term Depression Induced by Optogenetically Driven Nociceptive Inputs to Trigeminal Nucleus Caudalis or Headache Triggers.. Journal of Neuroscience. 2018; 38 (34) : 7529-7540.|
|Lipscombe D, Lopez-Soto EJ Protected by a Fox.. Neuron/Neuron. 2018; 98 (1) : 3-5.|
|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)|
|Mustafá ER, López Soto EJ, Martínez Damonte V, Rodríguez SS, Lipscombe D, Raingo J Constitutive activity of the Ghrelin receptor reduces surface expression of voltage-gated Ca2+ channels in a CaVβ-dependent manner.. Journal of cell science. 2017; 130 (22) : 3907-3917.|
|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.|
|Andrade A, Hope J, Allen A, Yorgan V, Lipscombe D, Pan JQ A rare schizophrenia risk variant of CACNA1I disrupts Ca<sub>V</sub>3.3 channel activity.. Scientific reports. 2016; 6 : 34233.|
|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 D, Andrade A Calcium Channel CaVα₁ Splice Isoforms - Tissue Specificity and Drug Action.. Current molecular pharmacology. 2015; 8 (1) : 22-31.|
|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, Lorin M., Marangoudakis, Spiro, Raingo, Jesica, Liu, Xinyuan, Lipscombe, Diane, Hurt, Robert H. The inhibition of neuronal calcium ion channels by trace levels of yttrium released from carbon nanotubes.. Biomaterials/Biomaterials. 2009; 30 (31) : 6351-6357.|
|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.
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|
|Fallon, Justin||Professor of Medical Science, Professor of Psychiatry and Human Behavior|
|Hart, Anne||Professor of Neuroscience, Graduate Program Director for the Neuroscience Graduate Program, Vice Chair of Neuroscience|
|Jaworski, Alexander||June G. Zimmerman Assistant Professor of Brain Science|
|Kauer, Julie||Adjunct Professor of Molecular Pharmacology, Physiology and Biotechnology|
|Moore, Christopher||Associate Director of the Carney Institute of Brain Science, Professor of Neuroscience|
|Wharton, Kristi||Professor of Biology|
Director, Robert J. & Nancy D. Carney Institute for Brain Science
President, 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 in the Neuroscience Graduate Program Laboratory course.
|NEUR 2030 - Advanced Molecular and Cellular Neurobiology I|