Diane LipscombeProfessor of Neuroscience, Director of the Brown Institute for Brain Science (BIBS), Thomas J. Watson, Sr. Professor of Science
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.
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
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.
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.
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
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. Fall 2014, Fall 2015, Fall 2016.