Jason P. Weick
PhD, University of Minnesota
Assistant Scientist, Waisman Center
Waisman Center, Room 641A
1500 Highland Avenue
Madison, WI 53705
The goal of my research is to understand the functional development of human neurons and how those may be negatively regulated during disease or enhanced during therapeutic interventions. Using human embryonic stem cell (hESC)-derived neurons as a model system, we have delineated the temporal progression by which human neurons develop functional properties including: 1) action potentials, 2) voltage-gated currents, and 3) synaptic activity. Compared to rodent neurons we have found that human neurons require an extended time course to acquire the aforementioned properties, but that astrocyte co-culture can accelerate functional development of human neurons, suggesting a possible role for astrocytes in neuronal cell replacement therapies. In addition, I am currently working on methods to control the functional output of human neurons using minimally invasive optical stimulation techniques using Channelrhodopsin-2 (ChR2). We have successfully demonstrated the utility of this tool in human neurons and created a clonal cell line that expresses ChR2 under the control of the synapsin-1 promoter. We believe this line of research will have a two-fold significance. First, it will aid in the study of basic development and plasticity of human neurons, and it will accelerate our understanding of the ability of stem cell-derived neurons to integrate with pre-existing neural networks, a prerequisite for neuronal cell-replacement therapies.
Weick J.P., Johnson M.A., Skroch S.P., Williams J.C., Deisseroth K., Zhang S.C.. Functional Control of Transplantable Human ESC-Derived Neurons Via Optogenetic Targeting. Stem Cells 2010 Nov 28(11):2008-16. PMID: 20827747
Hu B.Y., Weick, J.P., Yu, J., Thomson, J.A., and Zhang, S.C. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4335-40. PMCID 20160098.
Weick, J.P., Johnson, M.A., and Zhang, S.C. Developmental regulation of human embryonic stem cell-derived neurons by calcium entry via transient receptor potential (Trp) Channels. Stem Cells 2009 Dec 27(12):2906–2916. PMCID: PMC2806495
Lavaute, T.M., Yoo, Y.D., Pankratz, M.T., Weick, J.P., Gerstner J.D., and Zhang, S.C. Regulation of neural specification from human embryonic stem cells by BMP and FGF.. Stem Cells 2009 Apr 23; 27(8):1741-1749. PMCID: PMC2789116
Groth, R.D.*, Weick, J.P.*, Bradley, K.T., Luoma, J.I., Aravmudan, B., Klug, J.R., Thomas, M.J., and Mermelstein, P.G. D1 Dopamine Dopamine Receptor Activation of NFAT-mediated Striatal Gene Expression. Eur J Neurosci. 2008 Jan; 27(1):31-42.
Johnson, M.A., Weick, J.P., Pearce, R.A., and Zhang, S.C. Functional Neural Development from Human Embryonic Stem Cells: Accelerated Synaptic Activity via Astrocyte Co-Culture. J. Neurosci. 2007 Mar 21; 27(12):3069-77. PMCID: PMC2735200
Weick, J.P., Kuo, S.P., and Mermelstein, P.G. L-type calcium channel regulation of neuronal gene expression. Cellscience Reviews. 2005 (1):44-57.
Boulware, M.I., Weick, J.P., Becklund, B.R., Kuo, S.P., Groth, R.D., and Mermelstein, P.G. Estradiol activates group I and II metabotropic glutamate receptors, leading to opposing influences on nuclear CREB phosphorylation. J. Neurosci. 2005 May 18; 25(20):5066-78.
Weick, J.P., Groth, R.D., Isaksen, A.L., and Mermelstein, P.G. Interactions with PDZ proteins are required for L-type calcium channels to activate cAMP response element-binding protein-dependent gene expression. J. Neurosci. 2003 Apr 15; 23(8):3446-56.
Weick, J. and Thorn, R.J. Effects of acute sublethal exposure to coumaphos or diazinon on acquisition and discrimination of odor stimuli in the honey bee (Hymenoptera: Apidae). J Econ Entomol. 2002 Apr; 95(2):227-36.