Indiana University
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Theodore R. Cummins, PhD

Professor of Pharmacology and Toxicology
Interim Chair, Department of Pharmacology and Toxicology

Research Interest 

I research the biophysics of ion channels and the role of ion channels in neurological diseases.

Education

1983

B.A. Chemistry | Swarthmore College | Swarthmore, PA

1985

M.S. Biomedical Engineering | Hartford Graduate Center | Hartford, CT

1993

M.A. Neuroscience | Yale University | New Haven, CT

1996

PhD Neuroscience | Yale University | New Haven, CT | Advisor: FJ Sigworth

1996-1998

Postdoctoral Fellow | Department of Neurology | Yale University School of Medicine | Mentor: SG Waxman

Honors

2010-present

Reviewing Editor, Frontiers in Pharmacology of Ion Channel and Channelopathies

2010

Recipient of the IUSM Trustee Teaching Award

2009-present

Member, NIH Study Section SCS 

2007

Recipient of the IUSM Trustee Teaching Award

2003-present

Associate Editor, Neuroscience Letters

2002-present

Member, Scientific Advisory Board for the Paralyzed Veterans of America Spinal Cord Research Foundation

Our main interest is the biophysics of ion channels and the role of ion channels in neurological diseases. Sodium channel mutations have been linked to several neurological disorders including skeletal muscle non-dystrophic myotonias, episodic ataxia and epilepsy. We have shown that mutations in the human skeletal muscle sodium channel, for example,

play a crucial role in the development of hyperkalemic periodic paralysis. Changes in the expression and properties of voltage-gated sodium channels are also thought to play important roles in chronic pain.

My lab uses electrophysiological, molecular biological and computer modeling techniques to study how specific voltage-gated sodium channels contribute to excitability and to neurological diseases. 

The long-term goals of my research are to develop a better understanding of the roles that ion channels in play in pathophysiological conditions and to develop strategies for the treatment of neurological disorders that involve ion channels.

Current work in my laboratory is focused on:

  1. Understanding the role of peripheral neuronal sodium channels in nociception and neuropathic pain. Specific sodium channels are predominantly expressed in nociceptive sensory neurons. My lab is examining how the activity of these sodium channels are affected by inflammatory mediators and neurotrophins.
     
  2. Investigating the role of sodium channels in genetic diseases. Sodium channel mutations have been identified in patients with epilepsy and skeletal muscle diseases. My lab characterizes the functional consequences of the different disease mutations in heterologous expression systems using patch-clamp techniques. We are also examining the effects of these mutant sodium channels on excitability in neurons and muscle cells.
     
  3. Molecular pharmacology of voltage-gated sodium channels. Several projects focus on understanding the sensitivity of sodium channels to specific pharmacologic agents. Identify local anesthetics and anticonvulsants that preferentially target sodium channels involved in pain sensations. Identify the molecular determinants of sodium channel sensitivity to pore blockers. Identify biological toxins from marine cone snail and tarantula venoms that specifically target voltage-gated sodium channels. These studies will provide information on the pharmacology of specific voltage-gated sodium channels that are thought to play important roles in epilepsy and pain and hopefully will contribute to the development of better treatments for these neurological disorders.

Selected Publications

  • Song W, Xiao Y, Chen H, Ashpole NM, Piekarz AD, Ma P, Hudmon A, Cummins TR, Shou W. The human Nav1.5 F1486 deletion associated with long QT syndrome leads to  impaired sodium channel inactivation and reduced lidocaine sensitivity. J  Physiol. 2012 Oct 15;590(Pt 20):5123-39. PMID: 22826127; PMCID: PMC3497567.     

  • Ashpole NM, Herren AW, Ginsburg KS, Brogan JD, Johnson DE, Cummins TR, Bers  DM, Hudmon A. Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates  cardiac sodium channel NaV1.5 gating by multiple phosphorylation sites. J Biol  Chem. 2012 Jun 8;287(24):19856-69. PMID: 22514276; PMCID: PMC3370170.     

  • Theile JW, Cummins TR. Recent developments regarding voltage-gated sodium  channel blockers for the treatment of inherited and acquired neuropathic pain  syndromes. Front Pharmacol. 2011;2:54. PMID: 22007172; PMCID: PMC3185237.     

  • Theile JW, Cummins TR. Inhibition of Navβ4 peptide-mediated resurgent sodium  currents in Nav1.7 channels by carbamazepine, riluzole, and anandamide. Mol  Pharmacol. 2011 Oct;80(4):724-34. PMID: 21788423; PMCID: PMC3187525.     

  • Xiao Y, Jackson JO 2nd, Liang S, Cummins TR. Common molecular determinants of   tarantula huwentoxin-IV inhibition of Na+ channel voltage sensors in domains II  and IV. J Biol Chem. 2011 Aug 5;286(31):27301-10 PMID: 21659528; PMCID: PMC3149324.     

  • Sheets PL, Jarecki BW, Cummins TR. Lidocaine reduces the transition to slow  inactivation in Na(v)1.7 voltage-gated sodium channels. Br J Pharmacol. 2011  Sep;164(2b):719-30. PMID: 21232038;  PMCID: PMC3188891.     

  • Theile JW, Jarecki BW, Piekarz AD, Cummins TR. Nav1.7 mutations associated  with paroxysmal extreme pain disorder, but not erythromelalgia, enhance Navbeta4 peptide-mediated resurgent sodium currents. J Physiol. 2011 Feb 1;589(Pt  3):597-608. PMID:  21115638; PMCID: PMC3055545.     

  • Xiao Y, Blumenthal K, Jackson JO 2nd, Liang S, Cummins TR. The tarantula  toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7  voltage sensors to inhibit channel activation and inactivation. Mol Pharmacol.  2010 Dec;78(6):1124-34. PMID: 20855463; PMCID: PMC2993464.     

  • Jarecki BW, Piekarz AD, Jackson JO 2nd, Cummins TR. Human voltage-gated sodium  channel mutations that cause inherited neuronal and muscle channelopathies  increase resurgent sodium currents. J Clin Invest. 2010 Jan;120(1):369-78. PMID: 20038812; PMCID:  PMC2799199.    

  • Xiao Y, Bingham JP, Zhu W, Moczydlowski E, Liang S, Cummins TR. Tarantula  huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and  trapping the domain ii voltage sensor in the closed configuration. J Biol Chem.  2008 Oct 3;283(40):27300-13. PMID: 18628201; PMCID: PMC2556013.    

  • Cummins TR, Sheets PL, Waxman SG. The roles of sodium channels in  nociception: Implications for mechanisms of pain. Pain. 2007 Oct;131(3):243-57.  PMID: 17766042; PMCID: PMC2055547.      

Row 1: Yucheng Xiao,  Zifan Pei, Cindy Nunez-Barbosa; Row 2: Andrew Piekarz, Ted Cummins, Tumare Iqbal, Jonathan Theile, James Jackson