FACULTY RESEARCH

Faculty List

Joy Audrey Umbach, Ph.D.

Work Email Address: jumbach@mednet.ucla.edu

Work Phone Number: 310-825-2973

Work Address:
CHS
Los Angeles, CA 90095

Department / Division Affiliations
Adjunct Associate Professor, Molecular & Medical Pharmacology

Research Interests
Research in my lab focuses on the molecular mechanism of neurotransmitter release. Central to this task is determining the role of specific proteins that participate in this process. One such protein is a novel synaptic vesicle constituent known as a cysteine string protein (csp). Using a variety of techniques including expression of cRNA in frog oocytes, electrophysiology, functional studies of mutant alleles of Drosophila and fluorescence imaging of calcium dynamics in presynaptic boutons, we have shown that csps are essential for the evoked release of neurotransmitter and that csps interact with the calcium channels that trigger release. To extend this work we are using co-cultures of Xenopus nerve and muscle cells. This preparation has the advantage that reagents (peptides, antibodies, enzymes) can be applied intracellularly via a patch pipette. One can then use electrophysiological and imaging approaches to characterize the effect of these agents on synaptic transmission and calcium channel function. In addition to understanding of the role of csps (and proteins with which csps interact) in presynaptic events, we have become interested in the mechanism by which lithium (Li) and other mood stabilizing drugs affect presynaptic function. This work is based on our findings that therapeutic levels of Li ions selectively up-regulate csp gene expression in both rat brain and differentiated PC12 cell cultures. We are using amperometry and radio-tracer flux measurements on PC12 cells to assay the functional consequences of this enhanced gene expression. In situ hybridization assays of rat brain are defining specific brain regions affected by drug treatment. Moreover, intracellular Li ion-sensitive electrodes and reporter protein assays are being used to gain insight into the mechanism by which Li and other drugs enhance gene expression. Ultimately, this work may afford insights into the cause and improved treatment of bipolar-affective disorders.

Figure 2: Xenopus presynaptic varicosity in
culture brightfield; fluorescence of calcium-
sensitive dye at rest; fluorescence after stimulation.

Figure 1: Fluorescence of calcium-
sensitive dye in synaptic boutons
on ventral longitudinal muscle
fibers of Drosophila.



Publications
Gundersen Cameron B, Kohan Sirus A, Souda Puneet, Whitelegge Julian P, Umbach Joy A Cysteine string protein beta is prominently associated with nerve terminals and secretory organelles in mouse brain. Brain research. 2010; 1332: 1-11.
Karumbayaram Saravanan, Novitch Bennett G, Patterson Michaela, Umbach Joy A, Richter Laura, Lindgren Anne, Conway Anne E, Clark Amander T, Goldman Steve A, Plath Kathrin, Wiedau-Pazos Martina, Kornblum Harley I, Lowry William E Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem cells (Dayton, Ohio). 2009; 27(4): 806-11.
Karumbayaram Saravanan, Kelly Theresa K, Paucar Andres A, Roe Anne J T, Umbach Joy A, Charles Andrew, Goldman Steven A, Kornblum Harley I, Wiedau-Pazos Martina Human embryonic stem cell-derived motor neurons expressing SOD1 mutants exhibit typical signs of motor neuron degeneration linked to ALS. Disease models & mechanisms. 2009; 2(3-4): 189-95.
Schietroma Cataldo, Yu Hoi-Ying, Wagner Mark C, Umbach Joy A, Bement William M, Gundersen Cameron B A role for myosin 1e in cortical granule exocytosis in Xenopus oocytes. The Journal of biological chemistry. 2007; 282(40): 29504-13.
Smith Geoffrey B, Umbach Joy A, Hirano Arlene, Gundersen Cameron B Interaction between constitutively expressed heat shock protein, Hsc 70, and cysteine string protein is important for cortical granule exocytosis in Xenopus oocytes. The Journal of biological chemistry. 2005; 280(38): 32669-75.
Umbach Joy A, Zhao Ying, Gundersen Cameron B Lithium enhances secretion from large dense-core vesicles in nerve growth factor-differentiated PC12 cells. Journal of neurochemistry. 2005; 94(5): 1306-14.
Cordeiro Mara L, Gundersen Cameron B, Umbach Joy A Convergent effects of lithium and valproate on the expression of proteins associated with large dense core vesicles in NGF-differentiated PC12 cells. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 2004; 29(1): 39-44.
Cordeiro, ML Gundersen, CB Umbach, JA Convergent effects of lithium and valproate on the expression of proteins associated with large dense core vesicles in NGF-differentiated PC12 cells. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. . 2004; 29(1): 39-44.
Cordeiro, ML Gundersen, CB Umbach, JA Dietary lithium induces regional increases of mRNA encoding cysteine string protein in rat brain. Journal of neuroscience research. . 2003; 73(6): 865-9.
Cordeiro Mara L, Gundersen Cameron B, Umbach Joy A Dietary lithium induces regional increases of mRNA encoding cysteine string protein in rat brain. Journal of neuroscience research. 2003; 73(6): 865-9.
Cordeiro, ML Gundersen, CB Umbach, JA Lithium ions modulate the expression of VMAT2 in rat brain. Brain research. . 2002; 953(1-2): 189-94.
Cordeiro Mara L, Gundersen Cameron B, Umbach Joy A Lithium ions modulate the expression of VMAT2 in rat brain. Brain research. 2002; 953(1-2): 189-94.
Mischel Paul S, Umbach Joy A, Eskandari Sepehr, Smith Shane G, Gundersen Cameron B, Zampighi Guido A Nerve growth factor signals via preexisting TrkA receptor oligomers. Biophysical journal. 2002; 83(2): 968-76.
Saitoe Minoru, Schwarz Thomas L, Umbach Joy A, Gundersen Cameron B, Kidokoro Yoshi Response: meaningless minis?. Trends in neurosciences. 2002; 25(8): 385-6.
Mischel PS, Umbach JA, Eskandari S, Smith SG, Gundersen CB, Zampighi GA Nerve growth factor signals via pre-existing TrkA receptor oligomers. Biophys J 2002; 83: 968-976.
Gundersen, CB Kohan, SA Chen, Q Iagnemma, J Umbach, JA Activation of protein kinase Ceta triggers cortical granule exocytosis in Xenopus oocytes. Journal of cell science. . 2002; 115(Pt 6): 1313-20.
Gundersen Cameron B, Kohan Sirus A, Chen Qian, Iagnemma Joseph, Umbach Joy A Activation of protein kinase Ceta triggers cortical granule exocytosis in Xenopus oocytes. Journal of cell science. 2002; 115(Pt 6): 1313-20.
Saitoe, M Schwarz, TL Umbach, JA Gundersen, CB Kidokoro, Y Absence of junctional glutamate receptor clusters in Drosophila mutants lacking spontaneous transmitter release. Science. . 2001; 293(5529): 514-7.
Gundersen, CB Aguado, F Sou, S Mastrogiacomo, A Coppola, T Kornblum, HI Umbach, JA Cysteine string proteins are associated with cortical granules of Xenopus laevis oocytes. Cell and tissue research. . 2001; 303(2): 211-9.
Cordeiro ML, Umbach JA, Gundersen CB Lithium ions up-regulate mRNAs encoding dense-core vesicle proteins in nerve growth factor-differentiated PC-12 cells. J Neurochem 2000; 75: 2622-2625.
Cordeiro, ML Umbach, JA Gundersen, CB Lithium ions enhance cysteine string protein gene expression in vivo and in vitro. Journal of neurochemistry. . 2000; 74(6): 2365-72.
Poage, RE Meriney, SD Gundersen, CB Umbach, JA Antibodies against cysteine string proteins inhibit evoked neurotransmitter release at Xenopus neuromuscular junctions. Journal of neurophysiology. . 1999; 82(1): 50-9.
Mastrogiacomo A, Kornblum HI, Umbach JA and Gundersen CB A Xenopus cysteine string protein with a cysteine residue in the J domain. Biochem. Biophys. Acta 1998; 1401: 239-241.
Umbach JA, Grasso A, Zurcher SD, Kornblum HI, Mastiogiacomo A, Gundersen CB. Electrical and optical monitoring of <font face = symbol>a</font>-latrotoxin action at Drosophila neuromuscular junctions. Neurosci 1998; 87: 913-924.
Umbach, JA Saitoe, M Kidokoro, Y Gundersen, CB Attenuated influx of calcium ions at nerve endings of csp and shibire mutant Drosophila. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 1998; 18(9): 3233-40.
Umbach JA and Gundersen CB Evidence that cysteine string proteins regulate an early step in the Ca-dependent secretion of neurotransmitter at Drosophila neuromuscular junctions. J. Neurosci 1997; 17: 7203-7209.
Gundersen, CB Umbach, JA Mastrogiacomo, A Cysteine-string proteins: a cycle of acylation and deacylation?. Life sciences. . 1996; 58(22): 2037-40.
Kohan, SA Pescatori, M Brecha, NC Mastrogiacomo, A Umbach, JA Gundersen, CB Cysteine string protein immunoreactivity in the nervous system and adrenal gland of rat. The Journal of neuroscience : the official journal of the Society for Neuroscience. . 1995; 15(9): 6230-8.
Umbach JA, Mastrogiacomo A, Gundersen CB Cysteine string proteins and presynaptic function. J Physiol 1995; 89: 95-101.