Ph.D., University of Kiel, Germany, 1998
Office Phone: 530-754-6135
Ion channels in the immune system Research Synopsis:
My laboratory studies the role of potassium channels in the immune system. Potassium channels are proteins that tunnel the outer membrane of cells allowing for the quick flow of potassium ions in and out of the cell. In human T and B lymphocytes the voltage-gated potassium channel Kv1.3 and the calcium-activated potassium channel IKCa1 are critically involved in regulation of membrane potential, calcium signaling and mitogen or antigen induced proliferation. Expression of these two channels changes dramatically as T and B cells differentiate from naïve into memory cells, allowing the selective targeting of memory T and B cells with Kv1.3 blocking compounds. Kv1.3 is therefore regarded as promising target for the treatment of autoimmune diseases such as multiple sclerosis and type-1 diabetes. Through a combination of synthetic medicinal chemistry and electrophysiology we have in the past designed a selective blocker for IKCa1 and are in the process of developing a small molecule Kv1.3 blocker. Another project in my lab is the study of the functional role of potassium channels in oncogenesis and the identification of possible new targets for the treatment of multiple myeloma and other lymphomas.
Baell J.B., Gable R.W., Harvey A.J., Toovey N., Herzog T., Hänsel W., Wulff H. (2004) Kellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: Synthesis and immunosuppressive activity. Journal of Medicinal Chemistry 47:2326-2336. Abstract.
Vennekamp J.*, Wulff H.* (*joint first authors), Beeton C., Calabresi P.A., Grissmer S., Hänsel W., Chandy K.G. (2004) Kv1.3 blocking 5-Phenylalkoxypsoralens: A new class of immunomodultors. Molecular Pharmacology. 65:1364-1374. Abstract.
Chandy K.G., Wulff H., Beeton C., Pennington M., Gutman G.A., Cahalan M.D. (2004) Potassium Channels as Targets for Specific Immunomodulation. Trends in Pharmacological Sciences 25:280-289. Abstract.
Mouhat S., Mosbah A., Visan V., Wulff H., Delepierre M., Darbon H., Grissmer S., De Waard M., and Sabatier J.-M. (2004) The "functional" dyad of scorpion toxin Pi1 is not itself a prerequisite for toxin binding to the voltage-gated Kv1.2 potassium channels. Biochemical Journal 377:25-36. Abstract.
Wulff H., Knaus H. G., Pennington M., and Chandy, K. G. (2004) K+ channel expression during B-cell differentiation: implications for immunomodulation and autoimmunity. Journal of Immunology 173:776-786. Abstract.
Mouhat S., Visan V., Ananthakrishnan S., Wulff H., Grissmer S., Darbon H., De Waard M., and Sabatier J.-M. (2004) K+ channel types targeted by synthetic OSK1, a toxin from Orthochirus scrobiculosus scorpion venom. Biochemical Journal 385:35-104. Abstract.
Beeton C, Pennington MW, Wulff H, Singh S, Nugent D, Crossley G, Khaytin I, Calabresi PA, Chen CY, Gutman GA, Chandy KG. (2005) Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases. Molecular Pharmacology 67:1369-81. Abstract.
Rus, H., Pardo, C. A., Hu, L., Darrah, E., Cudrici, C., Niculescu, T., Niculescu, F., Mullen, K. M., Allie, R., Guo, L., Wulff, H., Beeton, C., Judge, S. I., Kerr, D. A., Knaus, H. G., Chandy, K., G., Calabresi, P. A. (2005) The voltage-gated potassium channel Kv1.3 is highly expressed on inflammatory infiltrates in multiple sclerosis brain. Proc. Natl Acad Sci U S A 102:(31)11094-11099. Abstract
Schmitz, A., Sankaranarayanan, A., Azam, P., Schmidt-Lassen, K., Homerick, D., Hansel, W., Wulff, H. (2005) Design of PAP-1, a selective small molecule Kv1.3 blocker, for the supression of effector memory T cells in autoimmune diseases. Mol Pharmacol. 68(5)1254-1270. AbstractMouhat, S., Teodorescu, G., Homerick, D., Visan, V., Wulff, H., Wu, Y., Grissmer, S., Darbon, H., DeWaard, M., Sabatier, J. M. (2006) Pharmacological profiling of Orthochirus scrobiculosus toxin 1 analogues with a trimmed N-terminal domain. Mol Pharmacol. 69:(1)354-362. Abstract Harvey, A. J., Baell, J. B., Toovey, N., Homerick, D., Wulff, H. (2006) A new class of blockers of the voltage-gated potassium channel Kv1.3 via modification of the 4- or 7-position of khellinone. J Med Chem 49:(4)1433-1441. Abstract