Epilepsy, Sodium channels, Excitability, Model Systems–
For the past 29 years my research lab at UCI has studied the activity of living neurons from the brains of both flies and mice. Using molecular genetic manipulations and whole cell electrophysiology we are exploring the role of specific genes in regulating functional plasticity of developing and mature neural circuits. We are also examining how environmental factors such as exposure to specific drugs, including nicotine, can influence information transfer between neurons. A basic understanding of the genes and environmental factors that influence information processing between small groups of neurons is key to development of drugs and gene therapies aimed at restoring normal activity in the human brain that has been damaged by injury, disease, or exposure to drugs of abuse. These studies will also provide important clues as to the factors that might enhance normal cognitive function both during development and in the mature human brain.We are currently exploring the cellular mechanisms underlying generation of seizures caused by mutations in the human sodium channel gene, SCN1A. Knock-in transgenic flies, mice and induced human pluripotent stem cells are the three strategies we use to compare sodium channel activity and firing properties in neurons with and without the epilepsy causing mutations.
Teaching is also an important facet of my career. With resources provided by an HHMI Professorship we are working to transform the relationship between teaching and research at UCI, a setting where research tends to dominate, and teaching is often viewed a burdensome chore. We are developing strategies to help create dynamic learning environments in large biology classes that are compatible with the faculty building or maintaining successful research programs. We also provide training in interactive teaching for graduate student TAs teaching discussions and postdoctoral fellows mentoring undergraduates in research. Finally, we have a program aimed at increasing the number of undergraduate biology majors participating in education abroad, with a particular focus on recruiting students who are members of groups underrepresented in the sciences.
- Schutte, R.J., Y. Xie, N.N.Ng, P. Figueroa, A.T. Pham, and D.K. O’Dowd(2018) Astrocyte-enriched feeder layers from cryopreserved cells support differentiation of spontaneously active networks of human iPSC-derived neurons.J. Neurosci. Methods294: 91-101 PMID:28746822.
- Dennin, M, Z.D. Schultz, A. Feig, N. Finkelstein, A.F. Greenhoot, M. Hildreth, A.K. Leibovich, J.D. Martin, M.B. Moldwin, D.K. O’Dowd, L.A. Posey, T.L. Smith, and E.R. Miller (2017) Aligning practice to policies: Changing the culture to recognize and reward teaching at research universities. CBE-Life Sciences Education16 (4): es5, 1-8.
- Xie, Y., R. J. Schutte, N.N. Ng, K.C. Ess, P.H. Schwartz and D.K. O’Dowd(2017). Reproducible and efficient generation of functionally active neurons from human hIPSCs for preclinical disease modeling. Stem Cell Research26: 84-94.
- Guven-Ozkan, T., G.U. Busto, S.S. Schutte, I. Cervantes-Sandoval, D.K.O’Dowd, and R.L. Davis (2016) MiR-980 is a memory suppressor microRNA that regulates the autism-susceptibility gene A2bp1. Cell Rep 14: 1698-709. PMID: 26876166
- Schutte, S.S., R.J. Schutte, E.V. Barragan, and D.K. O’Dowd(2016) Model systems for studying cellular mechanisms of SCN1A related epilepsy. J. Neurophysiol. 115: 1755-1766. PMID: 26843603
- Williams, A.E., N. M. Aguilar-Roca, and D.K. O’Dowd(2016) Lecture capture podcasts: differential student use and performance in a large introductory course. Education Technology Research and Development64: 1-12. DOI 10.1007/s11423-015-9406-5.
- Reimer, L., K. Schenke, T. Nguyen, D. K. O’Dowd, T. Domina, and M. Waschauer (2016) Evaluating promising practices in undergraduate STEM lecture courses. The Russell Sage Foundation Journal of the Social Sciences2: 212-233.
- Schutte, Ryan J., S.S. Schutte, J.Algara, E.V. Barragan, J.Gilligan, Cynthia Staber, Yiannis A. Savva, Martin A. Smith, Robert Reenan, and Diane K. O’Dowd (2014) Knock-in model of Dravet Syndrome reveals a constitutive and conditional reduction in sodium current. J. Neurophysiol. 112: 903-912. PMID: 24805083
- Brick, D.J., H.E. Nethercott, S. Montesano, M.G. Banuelos, A.E. Stover, S.S. Schutte, D. K. O’Dowd, R. J. Hagerman, M. Ono, D.R. Hessl, F. Tassone, and P.H. Schwartz (2014) The autism spectrum disorders stem cell resource at CHOC Children’s: Implication for disease modeling and drug discovery. Stem Cells Translational Medicine 3: 1275-1286. PMID: 25273538
- Narayanareddy, B.R.J, S. Vartiainen, N. Hariri, D.K. O’Dowd and S.P. Gross(2014) A biophysical analysis of mitochondrial movement: differences between transport in neuronal cell bodies versus processes. Traffic 15: 762-71. PMID 24673933
- Jiang*, S., A.E. Williams*, M. Warschauer, W. He, and D.K.O’Dowd (2014) Influence of incentives on performance in a Pre-college Biology MOOC. International Review of Research in Open and Distance Learning (IRRODL), 15.5 (*co-first authors).
- Iniguez, J., S.S. Schutte, and D.K. O’Dowd (2013) Cav3-type α1T calcium channels mediate transient calcium currents that regulate repetitive firing in Drosophila antennal lobe PNs. J. Neurophysiol. 110: 1490-1496 PMID: 23864373
- Stover, A., D. Brick, H. Nethercott, M. Banuelos, L. Sun, D. K. O’Dowd, and P. Schwartz (2013) Process-based expansion and neural differentation of human pluripotent stem cells for transplantation and disease-modeling. J. Neurosci. Res 91: 1247-1262. PMID: 23893392
- Sun, L., J. Gilligan, C. Staber, R.J. Schutte, V. Nguyen, D.K.O’Dowd* and R. Reenan* (2012) A knock-in model of human epilepsy in Drosophila reveals a novel cellular mechanism associated with heat-induced seizure. J. Neurosci. 32: 14145-14155. *co-corresponding authors
- Aguilar-Roca, N.M., A. E. Williams, and D.K. O’Dowd (2012) The impact of laptop-free zones on student performance and attitudes in large lectures. Computers & Education, in press.
- William, A., N.M. Aguilar-Roca, M. Tsai, M. Wong, M. Moravec Beaupré, and D. K. O’Dowd (2011) Assessment of learning gains associated with independent exam analysis in introductory biology. CBE-Life Science Education 10: 346-356. PMC3228653
- Ren, P., H. Zhang, F. Qiu, Y.Q. Liu, H. Gu, D.K. O’Dowd, Q.Y. Zhou, and W.P. Hu. (2011) Prokineticin 2 regulates the electrical activity of rat suprachiasmatic nuclei neurons. PloSOne 6:(6):e20263. PMC3110640.
- Anderson, W.A., U. Banerjee, C.L. Drennan, S.C.R. Elgin, I.R. Epstein, J. Handelsman, G.F. Hatfull, R. Losick*, D.K. O’Dowd*, B.M. Olivera, S.A. Strobel, G.C. Walker, and I.M. Warner (2011) Changing the Culture of Science Education at Research Universities. Science 331: 152-153. *corresponding authors.
- Moravec, M, A. Williams, N. Aguilar-Roca, D.K. O’Dowd (2010) Learn before lecture: A strategy that improves learning outcomes in a large introductory biology class. CBE-Life Science Education 9: 473-481. PMC2995765
- Gu*, H., S.A. Jiang*, J.M. Campusano*, J. Iniguez*, H. Su, A.A. Hoang, M. Lavian, X. Sun, and D.K.O’Dowd (2009) Cav2-type calcium channels encoded by cac regulate AP-independent neurotransmitter release at cholinergic synapses in adult Drosophila brain. J. Neurophysiol. 101: 42-53. * authors contributed equally. PMC2637009
- Sheeba, V.*, H. Gu*, V.K. Sharma, D.K.O’Dowd, and T. Holmes (2008) Circadian- and light-dependent regulation of resting membrane potential and spontaneous action potential firing of Drosophila circadian pacemaker neurons. J. Neurophysiol. 99: 976-88. *authors contributed equally to the work. PMC2692874
- Oh, H-W, J,M. Campusano, L.G.W. Hilgenberg, X. Sun, M.A. Smith, and D.K. O’Dowd (2008) Ultrastructural analysis of chemical synapses and gap junctions between Drosophila brain neurons in culture. Dev. Neurobiology 68: 281-294.
- Gu, H. and D.K. O’Dowd (2006) Cholinergic synaptic transmission in Drosophila Kenyon cells in situ. J. Neurosci. 26: 265-272. PMID: 16399696
- Hilgenberg, L.G.W, H. Su, H. Gu, D.K.O’Dowd, and M.A. Smith (2006) a3Na+/K+-ATPase is a neuronal receptor for agrin. Cell 125: 359-369. PMID: 16630822