Heike Wulff

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint K+ channel expression during B cell differentiation: implications for immunomodulation and autoimmunity
    Heike Wulff
    Department of Medical Pharmacology and Toxicology, University of California, Davis, CA 95616, USA
    J Immunol 173:776-86. 2004
  2. pmc K+ channels as targets for specific immunomodulation
    K George Chandy
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Trends Pharmacol Sci 25:280-9. 2004
  3. pmc Targeting effector memory T cells with the small molecule Kv1.3 blocker PAP-1 suppresses allergic contact dermatitis
    Philippe Azam
    Department of Medical Pharmacology and Toxicology, University of California, Davis, California 95616, USA
    J Invest Dermatol 127:1419-29. 2007
  4. pmc Potassium channel block by a tripartite complex of two cationophilic ligands and a potassium ion
    Pavel I Zimin
    Department of Pharmacology, University of California, Davis, California, USA
    Mol Pharmacol 78:588-99. 2010
  5. pmc Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases
    Christine Beeton
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 103:17414-9. 2006
  6. ncbi request reprint A novel fluorescent toxin to detect and investigate Kv1.3 channel up-regulation in chronically activated T lymphocytes
    Christine Beeton
    Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA
    J Biol Chem 278:9928-37. 2003
  7. pmc 4-Phenoxybutoxy-substituted heterocycles--a structure-activity relationship study of blockers of the lymphocyte potassium channel Kv1.3
    Silke B Bodendiek
    Department of Pharmacology, University of California, Davis, Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616, USA
    Eur J Med Chem 44:1838-52. 2009
  8. ncbi request reprint Potassium channels as therapeutic targets for autoimmune disorders
    Heike Wulff
    University of California, Davis Department of Pharmacology and Toxicology, School of Medicine, Tupper Hall, One Shields Avenue, Davis, CA 95616, USA
    Curr Opin Drug Discov Devel 6:640-7. 2003
  9. ncbi request reprint Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases
    Alexander Schmitz
    Department of Medical Pharmacology and Toxicology, Genome and Biomedical Sciences Facility, Room 3502, 451 East Health Sciences Drive, University of California, Davis, Davis, CA 95616, USA
    Mol Pharmacol 68:1254-70. 2005
  10. ncbi request reprint Targeting effector memory T-cells with Kv1.3 blockers
    Heike Wulff
    University of California, Davis, Department of Medical Pharmacology, School of Medicine, Genome and Biomedical Sciences Facility, Davis, CA 95616, USA
    Curr Opin Drug Discov Devel 10:438-45. 2007

Collaborators

Detail Information

Publications39

  1. ncbi request reprint K+ channel expression during B cell differentiation: implications for immunomodulation and autoimmunity
    Heike Wulff
    Department of Medical Pharmacology and Toxicology, University of California, Davis, CA 95616, USA
    J Immunol 173:776-86. 2004
    ..These changes parallel those reported for T cells. Therefore, specific Kv1.3 and IKCa1 inhibitors may have use in therapeutic manipulation of selective lymphocyte subsets in immunological disorders...
  2. pmc K+ channels as targets for specific immunomodulation
    K George Chandy
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Trends Pharmacol Sci 25:280-9. 2004
    ..3 and IKCa1 channels, and provide a rationale for the potential therapeutic use of these inhibitors in immunological disorders...
  3. pmc Targeting effector memory T cells with the small molecule Kv1.3 blocker PAP-1 suppresses allergic contact dermatitis
    Philippe Azam
    Department of Medical Pharmacology and Toxicology, University of California, Davis, California 95616, USA
    J Invest Dermatol 127:1419-29. 2007
    ..Based on these results we propose that PAP-1 could potentially be developed into a drug for the topical treatment of inflammatory skin diseases such as psoriasis...
  4. pmc Potassium channel block by a tripartite complex of two cationophilic ligands and a potassium ion
    Pavel I Zimin
    Department of Pharmacology, University of California, Davis, California, USA
    Mol Pharmacol 78:588-99. 2010
    ..Our study provides a new concept for potassium channel block by cationophilic ligands...
  5. pmc Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases
    Christine Beeton
    Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA
    Proc Natl Acad Sci U S A 103:17414-9. 2006
    ..Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted...
  6. ncbi request reprint A novel fluorescent toxin to detect and investigate Kv1.3 channel up-regulation in chronically activated T lymphocytes
    Christine Beeton
    Department of Physiology and Biophysics, University of California, Irvine, California 92697, USA
    J Biol Chem 278:9928-37. 2003
    ..3 up-regulation. ShK-F6CA might be useful for rapid and quantitative detection of Kv1.3(high) expressing cells in normal and diseased tissues, and to visualize the distribution of functional channels in intact cells...
  7. pmc 4-Phenoxybutoxy-substituted heterocycles--a structure-activity relationship study of blockers of the lymphocyte potassium channel Kv1.3
    Silke B Bodendiek
    Department of Pharmacology, University of California, Davis, Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616, USA
    Eur J Med Chem 44:1838-52. 2009
    ..Taken together, our results demonstrate that the psoralen system is a crucial part of the pharmacophore of phenoxyalkoxypsoralen-type Kv1.3 blockers...
  8. ncbi request reprint Potassium channels as therapeutic targets for autoimmune disorders
    Heike Wulff
    University of California, Davis Department of Pharmacology and Toxicology, School of Medicine, Tupper Hall, One Shields Avenue, Davis, CA 95616, USA
    Curr Opin Drug Discov Devel 6:640-7. 2003
    ..3 blockers for the therapy of T-cell mediated autoimmune diseases...
  9. ncbi request reprint Design of PAP-1, a selective small molecule Kv1.3 blocker, for the suppression of effector memory T cells in autoimmune diseases
    Alexander Schmitz
    Department of Medical Pharmacology and Toxicology, Genome and Biomedical Sciences Facility, Room 3502, 451 East Health Sciences Drive, University of California, Davis, Davis, CA 95616, USA
    Mol Pharmacol 68:1254-70. 2005
    ..PAP-1 and several of its derivatives therefore constitute excellent new tools to further explore Kv1.3 as a target for immunosuppression and could potentially be developed into orally available immunomodulators...
  10. ncbi request reprint Targeting effector memory T-cells with Kv1.3 blockers
    Heike Wulff
    University of California, Davis, Department of Medical Pharmacology, School of Medicine, Genome and Biomedical Sciences Facility, Davis, CA 95616, USA
    Curr Opin Drug Discov Devel 10:438-45. 2007
    ..3 in autoimmune diseases, reviews the progress made in both developing peptidic and small-molecule inhibitors for this challenging target, and in validating Kv1.3 as a target for the treatment of autoimmune diseases...
  11. ncbi request reprint AMA production in primary biliary cirrhosis is promoted by the TLR9 ligand CpG and suppressed by potassium channel blockers
    Yuki Moritoki
    Division of Rheumatology, Allergy, and Clinical Immunology and the University of California at Davis, Davis, CA 95616, USA
    Hepatology 45:314-22. 2007
    ..Conclusion: These data suggest that the hyperresponsiveness of B cells in PBC accelerates B cell-mediated autoimmunity...
  12. pmc K+ channel modulators for the treatment of neurological disorders and autoimmune diseases
    Heike Wulff
    Department of Pharmacology, University of California, Davis, California 95616, USA
    Chem Rev 108:1744-73. 2008
  13. ncbi request reprint Modulators of small- and intermediate-conductance calcium-activated potassium channels and their therapeutic indications
    Heike Wulff
    Department of Medical Pharmacology and Toxicology, University of California, Davis, CA 95616, USA
    Curr Med Chem 14:1437-57. 2007
    ..1 as a target for the treatment of traumatic and possibly ischemic brain injury. Taken together KCa2 and KCa3.1 channels constitute attractive new targets for several diseases that currently have no effective therapies...
  14. doi request reprint New light on the "old" chloride channel blocker DIDS
    Heike Wulff
    Department of Pharmacology, University of California, Davis, 451 Health Sciences Drive, Davis, California 95616, USA
    ACS Chem Biol 3:399-401. 2008
    ..The DIDS tetra- and pentamer could potentially act as tethered blockers that simultaneously obstruct both chloride pathways in the dimeric CLC proteins...
  15. pmc Endothelial small-conductance and intermediate-conductance KCa channels: an update on their pharmacology and usefulness as cardiovascular targets
    Heike Wulff
    Department of Pharmacology, University of California, Davis, CA 95616, USA
    J Cardiovasc Pharmacol 61:102-12. 2013
    ..1 and KCa2.3 modulators and critically assess the potential of KCa activators for the treatment of diabetes and cardiovascular diseases by improving endothelium-derived hyperpolarizations...
  16. pmc The KCa3.1 blocker TRAM-34 reduces infarction and neurological deficit in a rat model of ischemia/reperfusion stroke
    Yi Je Chen
    Department of Pharmacology, Genome and Biomedical Sciences Facility, University of California, Davis, California 95616, USA
    J Cereb Blood Flow Metab 31:2363-74. 2011
    ..Our findings suggest that KCa3.1 blockade constitutes an attractive approach for the treatment of ischemic stroke because it is still effective when initiated 12 hours after the insult...
  17. pmc Spiro azepane-oxazolidinones as Kv1.3 potassium channel blockers: WO2010066840
    Heike Wulff
    University of California, Department of Pharmacology, Davis, Davis, CA 95616, USA
    Expert Opin Ther Pat 20:1759-65. 2010
    ..This article briefly summarizes the chemistry and biological data provided in the patent and then compares the new compounds to Kv1.3 blockers previously disclosed by both academia and pharmaceutical companies...
  18. pmc Voltage-gated potassium channels as therapeutic targets
    Heike Wulff
    Department of Pharmacology, University of California, Davis, 451 Health Sciences Drive, GBSF Room 3502, Davis, California 95616, USA
    Nat Rev Drug Discov 8:982-1001. 2009
    ..1 (also known as EAG1 and KCNH1) and K(V)11.1 (also known as HERG and KCNH2) channels...
  19. pmc Naphtho[1,2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure
    Ananthakrishnan Sankaranarayanan
    Department of Pharmacology, University of California, Davis, California 95616, USA
    Mol Pharmacol 75:281-95. 2009
    ..The blood pressure-lowering effect of SKA-31 suggests KCa3.1 channel activation as a new therapeutic principle for the treatment of hypertension...
  20. pmc Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity
    Izumi Maezawa
    Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, California 95618, USA
    J Biol Chem 286:3693-706. 2011
    ..Our results suggest that AβO, generally considered a neurotoxin, may more potently cause neuronal damage indirectly by activating microglia in AD...
  21. pmc A simple device to illustrate the Einthoven triangle
    Benjamin E Jin
    Department of Pharmacology, University of California, Davis, 95616, USA
    Adv Physiol Educ 36:319-24. 2012
    ..Combined with traditional demonstrations with ECG machines, this equipment demonstrated its ability to help medical students obtain a solid foundation of the basic principles of electrocardiography...
  22. pmc Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer's Disease
    Izumi Maezawa
    Department of Pathology and Laboratory Medicine, University of California Davis, Davis, CA 95616, USA
    Int J Alzheimers Dis 2012:868972. 2012
    ..1 blockers are well known, and a KCa3.1 blocker has been proven safe in clinical trials. It is therefore promising to reposition old or new KCa3.1 blockers for AD preclinical and clinical trials...
  23. pmc Therapeutic potential of K(Ca)3.1 blockers: recent advances and promising trends
    Heike Wulff
    University of California, Davis, CA, USA
    Expert Rev Clin Pharmacol 3:385-96. 2010
    ..This article will review the physiology and pharmacology of K(Ca)3.1 and critically examine the available preclinical and clinical data validating K(Ca)3.1 as a therapeutic target...
  24. ncbi request reprint Modulation of mouse Paneth cell alpha-defensin secretion by mIKCa1, a Ca2+-activated, intermediate conductance potassium channel
    Tokiyoshi Ayabe
    Department of Pathology, College of Medicine, University of California, Irvine, California 92697 4800, USA
    J Biol Chem 277:3793-800. 2002
    ..These results demonstrate that mIKCa1 is modulator of Paneth cell alpha-defensin secretion and disclose an involvement in mucosal defense of the intestinal epithelium against ingested bacterial pathogens...
  25. ncbi request reprint Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases
    Christine Beeton
    Department of Physiology and Biophysics, 291 Irvine Hall, Medical School, University of California Irvine, Irvine, CA 92697 4561, USA
    Mol Pharmacol 67:1369-81. 2005
    ..ShK(L5) prevents and treats experimental autoimmune encephalomyelitis and suppresses delayed type hypersensitivity in rats. ShK(L5) might prove useful for therapy of autoimmune disorders...
  26. ncbi request reprint A new class of blockers of the voltage-gated potassium channel Kv1.3 via modification of the 4- or 7-position of khellinone
    Andrew J Harvey
    The Walter and Eliza Hall Institute of Medical Research Biotechnology Centre, 4 Research Avenue, La Trobe R and D Park, Bundoora 3086, Australia
    J Med Chem 49:1433-41. 2006
    ..3 with EC50 values of 480 and 400 nM, respectively. Both compounds exhibit moderate selectivity over other Kv1-family channels and HERG, are not cytotoxic, and suppress human T cell proliferation at low micromolar concentrations...
  27. pmc The voltage-gated Kv1.3 K(+) channel in effector memory T cells as new target for MS
    Heike Wulff
    Department of Physiology and Biophysics, University of California Irvine, College of Medicine, Irvine, California 92697, USA
    J Clin Invest 111:1703-13. 2003
    ..Selective targeting of Kv1.3 in T(EM) cells may therefore hold therapeutic promise for MS and other T cell-mediated autoimmune diseases...
  28. ncbi request reprint Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis
    Ralf Köhler
    Department of Nephrology, Benjamin Franklin Medical Center, Berlin, Germany
    Circulation 108:1119-25. 2003
    ..In a rat model of balloon catheter injury (BCI), we investigated whether alterations in expression of Ca2+-activated K+ channels (KCa) contribute to intimal hyperplasia and vascular restenosis...
  29. pmc The 'functional' dyad of scorpion toxin Pi1 is not itself a prerequisite for toxin binding to the voltage-gated Kv1.2 potassium channels
    Stephanie Mouhat
    Laboratoire International Associé d Ingénierie Biomoléculaire, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France
    Biochem J 377:25-36. 2004
    ..2 channels support an unexpected key role of specific basic amino acid residues, which form a basic ring (Arg-5, Arg-12, Arg-28 and Lys-31 residues), in toxin binding...
  30. ncbi request reprint Kv1.3-blocking 5-phenylalkoxypsoralens: a new class of immunomodulators
    Julia Vennekamp
    Pharmaceutical Institute, University of Kiel, Germany
    Mol Pharmacol 65:1364-74. 2004
    ..3 blockers may be useful as immunomodulators for the therapy of autoimmune disorders...
  31. ncbi request reprint Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: synthesis and immunosuppressive activity
    Jonathan B Baell
    The Walter and Eliza Hall Institute of Medical Research Biotechnology Centre, 4 Research Avenue, La Trobe R and D Park, Bundoora 3086, Australia
    J Med Chem 47:2326-36. 2004
    ..3, aryl-substituted khellinone derivatives represent attractive lead compounds for the development of more potent and selective Kv1.3 blocking immunosuppressants...
  32. pmc The voltage-gated potassium channel Kv1.3 is highly expressed on inflammatory infiltrates in multiple sclerosis brain
    Horea Rus
    Department of Neurology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA
    Proc Natl Acad Sci U S A 102:11094-9. 2005
    ..3(high)/CCR7(-) T(EM), suggesting that a subset of cerebrospinal fluid cells existed in a primed state ready to become T(EM). These studies provide further rationale for the use of specific Kv1.3 antagonists in MS...
  33. ncbi request reprint Potassium channel blockade by the sea anemone toxin ShK for the treatment of multiple sclerosis and other autoimmune diseases
    Raymond S Norton
    Walter and Eliza Hall Institute of Medical Research, Parkville 3052, Victoria, Australia
    Curr Med Chem 11:3041-52. 2004
    ..ShK and its analogs are currently undergoing further evaluation as leads in the development of new biopharmaceuticals for the treatment of multiple sclerosis and other T-cell mediated autoimmune disorders...
  34. pmc Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1
    Shekhar Srivastava
    Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 105:14442-6. 2008
    ....
  35. pmc The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to atherogenesis in mice and humans
    Kazuyoshi Toyama
    Department of Medicine and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    J Clin Invest 118:3025-37. 2008
    ..These data suggest that KCa3.1 blockers represent a promising therapeutic strategy for atherosclerosis...
  36. ncbi request reprint International Union of Pharmacology. LII. Nomenclature and molecular relationships of calcium-activated potassium channels
    Aguan D Wei
    Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Pharmacol Rev 57:463-72. 2005
  37. pmc K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom
    Stephanie Mouhat
    Laboratoire Cellpep S A, 13 15 Rue Ledru Rollin, 13015 Marseille, France
    Biochem J 385:95-104. 2005
    ..3 channel, with an IC50 value of 0.003 nM, without loss of activity on K(Ca)3.1 channel. These data suggest that OSK1 or [K16,D20]-OSK1 could serve as leads for the design and production of new immunosuppressive drugs...
  38. ncbi request reprint Characterisation of the human voltage-gated potassium channel gene, KCNA7, a candidate gene for inherited cardiac disorders, and its exclusion as cause of progressive familial heart block I (PFHBI)
    Soraya Bardien-Kruger
    University of Stellenbosch Medical Research Council Centre for Molecular and Cellular Biology, Department of Medical Physiology and Biochemistry, University of Stellenbosch Medical School, Tygerberg, South Africa
    Eur J Hum Genet 10:36-43. 2002
    ..As ion channel-encoding genes have been implicated in a growing number of genetic conditions, the data presented may facilitate further analysis of the role of KCNA7 and its product in the heart...
  39. ncbi request reprint International Union of Pharmacology. XLI. Compendium of voltage-gated ion channels: potassium channels
    George A Gutman
    Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, CA 92697, USA
    Pharmacol Rev 55:583-6. 2003
    ..The complete Compendium, including data tables for each member of the potassium channel family can be found at http://www.iuphar-db.org/iuphar-ic/...