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Diane Lipscombe, Ph.D., University College London

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Title: Professor of Neuroscience
Department: Neuroscience

Diane_Lipscombe@Brown.EDU
+1 401 863 1092, +1 401 863 1054

 
Overview | Research | Grants/Awards | Teaching | Publications

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.

Biography

I graduated with a PhD in Pharmacology from University College London in 1986. My journey into the world of calcium ion channels started when I joined Richard 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 here at Brown where I work closely with undergraduate and graduate students, as well as postdoctoral trainees. I direct the Neuroscience Graduate Program.

Institutions

Bu

Research Description

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

Select publications

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.

Fairbrother, W & Lipscombe, D (2008). Repressing the neuron within. Bioessays 30:1-4

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.

Gray AC, Raingo J, Lipscombe D. (2007) Neuronal calcium channels: Splicing for optimal performance. Cell Calcium 42:409-417.

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.

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.

Awards

1989-1990 Postdoctoral Fellow of the American Heart Association.
1995 Steinbach MBL Summer Fellowship
1996-2001 Research Career Development Award, K02
1998-1999 Richard and Edna Salomon Assistant Professor
1999-2003 Member MDCN-3 NIH Study Section
2001-2004 Council Member, Society of General Physiologists
2002 Catherine Filene Shouse MBL Summer Fellowship
2002-present Editorial Board Journal of Neurophysiology
2003-2007 Editorial Board, Reviewing Editor Journal of
Neuroscience
2007-2011 Member Publications Committee, Society for
Neuroscience
2007 Daniel A. Nachshen Memorial Lecturer, University of
Maryland Baltimore
2009 Harriet W Sheridan Award for Distinguished
Contribution to Teaching at Brown
2010 Graduate School Faculty Award for Advising and
Mentoring
2009-2011 Member Board Butler Hospital, Providence, RI
2010 Editorial Board of Wiley Interdisciplinary Reviews:
Membrane Transport Signaling.
2010-present Senior Editor, Brain Research
2010-2016 Member NIH BPNS Study Section
2011 Incoming Chair, Publications Committee, Society for
Neuroscience
2011 Robert Whitney Newcomb Memorial lecture, NINDS, NIH
2012 Joan Mott Prize Lecture, Physiological Society

Affiliations

Member of the Board of Butler Hospital, Providence, RI
Editorial Board: Journal of Neurophysiology
Member: Publication Committee Society for Neuroscience
Member: Society for Neuroscience
Member: AAAS

Funded Research

2010-2012 "Single nucleotide polymorphisms of neuronal CACNA1C L-type calcium channels Associated with biopolar disorder"
Principle Investigator: Diane Lipscombe
Agency: NIH NIMH
Type: R21 MH087969
12/1/10-11/30/12

1997-2011 "Neuronal Ca channels: Regulation and Function".
Principle Investigator: Diane Lipscombe
Agency: NIH NINDS
Type: R01 NS29967 (Years 14-17)
Current Period 1/1/06 -12/31/11

2009-2011: "Neuronal Ca channels: Regulation and Function".
Principle Investigator: Diane Lipscombe
Agency: NIH NINDS
Type: 3R01NS029967-17S1 (ARRA supplemental award)
Budget period: 07/21/2009 – 08/31/2010

2006-2014 "N-type calcium channel in nociceptive neurons"
Principle Investigator: Diane Lipscombe
Agency: NIH NINDS
Type: R01 NS055251-01
Period: 08/02/2006 – 01/31/2014 (Current budget years 5-9)

2009-2011 "N-type calcium channels in nociceptive neurons"
Principle Investigator: Diane Lipscombe
Agency: NIH NINDS
Type: 3R01NS055251-04S1 (ARRA supplemental award)
Budget Period: 02/01/2009 – 02/14/2010

2011-2016 "Predoctoral Training Program in Neuroscience"
Principle Investigator: Diane Lipscombe
Agency NIH-NIMH
Type: T32MH020068 (Years 11-16)
Period 7/1/11-6/30/16

Teaching Experience

I was honored to receive the 2008 Harriet W. Sheridan Award for Distinguished Contribution to Teaching and Learning at Brown.

I direct the Neuroscience Graduate Program.

I teach one of the 1st year core graduate courses BN203. This course explores cellular and molecular neurobiology.

I co-organize a graduate level "Bench to Bedside" course with Dr. Stephen Rasmussen, Butler Hospital.

I also organize a skills workshop series for the graduate students.

Courses Taught

  • Advanced Cellular and Molecular Neurobiology (BN0204)
  • Advanced Molecular and Cellular Neurobiology I (BN0203)

Selected Publications

  • Arturo Andrade, Sylvia Denome, Yu-Qiu Jiang, Spiro Marangoudakis, and Diane Lipscombe (2010). Opioid receptor inhibition of N-type calcium channels and spinal morphine analgesia couple to cell-specific alternative splicing. Nature Neuroscience. In press.(2010)
  • Lipscombe, D & Pan, JQ (2009). Tripping the HCN breaker. Neuron 62:747-750.(2009)
  • 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.(2009)
  • Andrade, A, Sandoval, A, Lipscombe, D, Campbell, KP & Felix, R (2009) The CaVα2δ subunit augments expression and modifies the pharmacology of CaV1.3 L-type channels. Cell Calcium, 46, 282-292.(2009)
  • Fairbrother, W & Lipscombe, D (2008). Repressing the neuron within. Bioessays 30:1-4(2008)
  • 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.(2007)
  • Gray AC, Raingo J, Lipscombe D. (2007) Neuronal calcium channels: Splicing for optimal performance. Cell Calcium. 42:4-5.(2007)
  • 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.(2007)
  • Lipscombe, D & Raingo, J (2007). Alternative Splicing Matters: N-type Calcium Channels in Nociceptors. Channels 1:225-227.(2007)
  • Lipscombe, D & Raingo, J (2006). Internalizing channels: a mechanism to control pain? Nature Neuroscience 9:8-10.(2006)
  • 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. Journal of Physiology. 576:119-134.(2006)
  • 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.(2006)
  • Helton, TD, Xu, W, & Lipscombe, D (2005). Neuronal L-type calcium channels open quickly and are blocked slowly. J. Neuroscience 25: 10247-10251.(2005)
  • Lipscombe, D. (2005) Ion channels. The Encyclopedia of Life Sciences. Macmillan Press.(2005)
  • Lipscombe, D (2005). Neuronal proteins custom designed by alternative splicing. Current Opinions in Neuroscience 15:358-363.(2005)
  • Lipscombe, D & Castiglioni, AJ (2004). Alternative splicing in voltage-gated calcium channels. In "Calcium Channel Pharmacology" Kluwer/ Academic/ Plenum Publishing. Ed. Stefan I McDonough.(2004)
  • 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.(2004)
  • Lipscombe, D., Xu, W. & Helton, TD. (2004) Neuronal L-type calcium channels: Get the low down. J. Neurophysiology 92:2633-2641.(2004)
  • Lin, Y, McDonough, SI, & Lipscombe, D. (2004) Alternative splicing in the voltage-sensing region of N -type CaV2.2 channels modulates channel activation and deactivation speed. J. Neurophysiology 92:2820-2830.(2004)
  • Thaler, C, Gray, AC & Lipscombe, D. (2004) Cumulative inactivation of N-type Cav2.2 calcium channels modified by alternative splicing. Proceedings of the National Academy of Science, USA. 101:5675-5679.(2004)
  • Lipscombe, D (2002) L-type calcium channels: Highs and new lows. Circulation Research. 90:933-935.(2002)
  • Lipscombe, D, Pan, QJ. & Gray, AC. (2002) Functional diversity in voltage-gated calcium channels generated by alternative splicing". Molecular Neurobiology 26:21-44.(2002)
  • Xu, W & Lipscombe, D. (2001) Neuronal CaV1.3alpha1 L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines. J. Neuroscience 21:5944-5951.(2001)
  • Pan, JQ & Lipscombe, D (2000). Alternative splicing in the II-III loop of the N-type Ca channel alpha1subunit: Functional differences are beta-subunit specific. J. Neuroscience 20:4769-4775.(2000)
  • Lipscombe, D. (2000) "Ion channels". The Encyclopedia of Life Sciences. Macmillan Press.(2000)
  • Schorge, S, Gupta, S, Lin, Z, McEnery, M & Lipscombe, D. (1999) Voltage and calcium-dependent stabilization of a Ca channel mRNA. Nature Neuroscience 2:785-790.(1999)
  • Lipscombe, D. (1999) Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons. J. Neuroscience 19:5322 5331.(1999)