UC Davis 111 project teaching team

Professor Isaac Pessah, Ph.D. Univ. Maryland

Associate Dean for Research and Graduate Education

Deputy Director, Center for Children’s Environmental Health and Disease Prevention

School of Veterinary Medicine

Dr. Pessah is a leading international expert on calcium signaling in brain and muscle cells and ryanodine receptor research.

Professor Isaac Pessah earned B.S. degrees in Cornell University in 1977.and holds an M.S. and Ph.D. in Toxicology from University Maryland and is an accomplished scientist and scholar. 2012 NIH Honor Isaac Pessah has accepted the invitation of the NIH Center for Scientific Review to serve in the Neurotoxicology and Alcohol Study Section from July 2012 through June 2016. Members are selected for the quality of their research accomplishments, publications in scientific journals, and other significant scientific activities, achievements and honors. Pessah’s participation is important in assuring the quality of the NIH peer review process. Membership in this group is both an honor and a major commitment of professional time and energy resulting in a unique opportunity to contribute to the national biomedical research effort.

Dr. Pessah is a toxicologist with research interest in the area of molecular and cellular mechanisms regulating signaling in excitable cells.  His current research focuses on the structure, function, and pharmacology of the ryanodine-sensitive calcium channels (RyRs) found in sarcoplasmic and endoplasmic reticulum of muscle cells and neurons. His laboratory is actively studying how dysfunction of RyR complexes contribute to genetic diseases and how genetic alteration of RyRs and environmental factors interact to influence neurodevelopment by utilizing cellular, biochemical and molecular investigations of calcium-signaling pathways. Dr. Pessah has developed a strong, collaborative and interdisciplinary research program with colleagues across the university, as well as nationally and internationally. He is director of The Center for Children’s Environmental Health and Disease Prevention, and a member of the MIND Institute.

Selective Publications:

1.      Niknam Y, Feng W, Cherednichenko G, Dong Y, Joshi SN, Vyas SM, Lehmler HJ, Pessah IN: Structure-activity relationship of selected meta- and para-hydroxylated non-dioxin like polychlorinated biphenyls: from single RyR1 channels to muscle dysfunction. Toxicol Sci 2013, 136:500-513.

2.      Girirajan S, Johnson RL, Tassone F, Balciuniene J, Katiyar N, Fox K, Baker C, Srikanth A, Yeoh KH, Khoo SJ, et al: Global increases in both common and rare copy number load associated with autism. Hum Mol Genet 2013, 22:2870-2880.

3. Cao Z, Hulsizer S, Cui Y, Pretto DL, Kim KH, Hagerman PJ, Tassone F, Pessah IN. Enhanced asynchronous Ca(2+) oscillations associated with impaired glutamate transport in cortical astrocytes expressing Fmr1 gene premutation expansion.  J Biol Chem. 2013 May 10;288(19):13831-41.

4.      Cherednichenko G, Zhang R, Bannister RA, Timofeyev V, Li N, Fritsch EB, Feng W, Barrientos GC, Schebb NH, Hammock BD, Pessah IN: Triclosan impairs excitation-contraction coupling and Ca2+ dynamics in striated muscle. Proc Natl Acad Sci U S A 2012, 109:14158-14163.

5.      Wayman GA, Bose DD, Yang D, Lesiak A, Bruun D, Impey S, Ledoux V, Pessah IN, Lein PJ: PCB-95 modulates the calcium-dependent signaling pathway responsible for activity-dependent dendritic growth. Environ Health Perspect 2012, 120:1003-1009.

6. Cao Z, Hulsizer S, Tassone F, Tang HT, Hagerman RJ, Rogawski MA, Hagerman PJ, Pessah IN. Clustered burst firing in FMR1 premutation hippocampal neurons: amelioration with allopregnanolone. Hum Mol Genet. 2012 Jul 1;21(13):2923-35.

7.      Kim KH, Bose DD, Ghogha A, Riehl J, Zhang R, Barnhart CD, Lein PJ, Pessah IN: Para- and ortho-substitutions are key determinants of polybrominated diphenyl ether activity toward ryanodine receptors and neurotoxicity. Environ Health Perspect 2011, 119:519-526.

8. Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz-Picciotto I, Tassone F, Pessah IN. Mitochondrial dysfunction in autism. JAMA. 2010 Dec 1;304(21):2389-96.

9. Chen Y, Tassone F, Berman RF, Hagerman PJ, Hagerman RJ, Willemsen R, Pessah IN. Murine hippocampal neurons expressing Fmr1 gene premutations show early developmental deficits and late degeneration. Hum Mol Genet. 2010 Jan 1;19(1):196-208.

10.    Chopra N, Yang T, Asghari P, Moore ED, Huke S, Akin B, Cattolica RA, Perez CF, Hlaing T, Knollmann-Ritschel BE, et al: Ablation of triadin causes loss of cardiac Ca2+ release units, impaired excitation-contraction coupling, and cardiac arrhythmias. Proc Natl Acad Sci U S A 2009, 106:7636-7641.

11.    Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN: The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect 2006, 114:1119-1125.

12.    Goth SR, Chu RA, Gregg JP, Cherednichenko G, Pessah IN: Uncoupling of ATP-mediated calcium signaling and dysregulated interleukin-6 secretion in dendritic cells by nanomolar thimerosal. Environ Health Perspect 2006, 114:1083-1091.

13. Cherednichenko G, Hurne AM, Fessenden JD, Lee EH, Allen PD, Beam KG, Pessah IN. Conformational activation of Ca2+ entry by depolarization of skeletal myotubes. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15793-8.

14. Gafni J, Munsch JA, Lam TH, Catlin MC, Costa LG, Molinski TF, Pessah IN. Xestospongins: potent membrane permeable blockers of the inositol 1,4,5-trisphosphate receptor. Neuron. 1997 Sep;19(3):723-33.

Professor Jie Zheng, Ph.D. Yale

Vice Chair for Research, Department of Physiology and Membrane Biology

School of Medicine

Dr. Zheng is a biophysicist specialized in membrane excitability and ion channels research, and the leading editor of the textbook Handbook of Ion Channels.

Professor Jie Zheng got B.S. And M.S.degrees in Peking University in 1991.and holds an Ph.D. degree in Physiology from University Yale University in 1998. Dr.Zheng is Editorial board member, Journal of General Physiology; Editorial board member, Protein & Cell; ad hoc reviewer, NIH; co-chair, AHA study section; ad hoc reviewer, BBSRC, United Kingdom; ad hoc reviewer, Italian Ministry of Health ; ad hoc reviewer, Hong Kong Research Grants Council ; ad hoc reviewer, Czech Science Foundation; ad hoc reviewer, Israel Science Foundation ; ad hoc reviewer, UC Davis School of Medicine Bridge Fund; ad hoc reviewer, UC Davis Cancer Center Pilot Grant.

Research in his lab is toward the Ion channels are membrane proteins that facilitate ion flux into or out of the cell or its organelles. They play critical roles in fundamental cellular functions such as neuronal signaling, muscle contraction, secretion, and fertilization. The long term goal of my research is to understand the molecular mechanisms underlying the opening and closing of the ion permeation pathway in channels, and how this process is controlled by various physical and chemical stimuli. Malfunctions of the ion channel activation process caused by genetic and pathological factors are the basis for numerous human diseases including long QT syndrome, cystic fibrosis, epilepsy, schizophrenia and deficiency in learning and memory. Research in my lab focuses on the heat activation of thermoTRP channels, which serve as biosensors for ambient temperature as well as noxious (painful) stimuli. We use multidisciplinary approaches to investigate the structural basis, functional properties, and regulation of the highly temperature-dependent activation process.

Selective Publications:

1. Yang, F., X. Xiao, W. Cheng, W. Yang, P. Yu, Z. Song, V. Yarov-Yarovoy, J. Zheng (2015), Structural mechanism underlying capsaicin binding and activation of nociceptive TRPV1 ion channel, Nature Chemical Biology, (in press)

2. Jie Zheng and Matthew C. Trudeau (editors), Handbook of Ion Channels, CRC Press

3. Tang, Y.Q., J.H. Zhou, F. Yang, J. Zheng, and K.W. Wang (2014) The tetramerization domain potentiates Kv4 channel function by suppressing closed-state inactivation, Biophysical Journal, 107: 1090-1104

4. Yang, F., and J. Zheng (2014) High temperature sensitivity is intrinsic to voltage-gated potassium channels, eLife, e03255

5. Ma, L., B.H. Lee, R. Mao, A. Cai, Y. Jia, H. Clifton, S. Schaefer, L. Xu, and J. Zheng (2014) Nicotinic acid activates the capsaicin receptor TRPV1 - a potential mechanism for cutaneous flushing, Arteriosclerosis, Thrombosis, and Vascular Biology, 34:1273-1280.

6. Yang, F., L. Ma, X. Cao, K.W. Wang, and J. Zheng. (2014) Divalent cations activate TRPV1 through promoting conformational change of the extracellular region, Journal of General Physiology, 143(1): 91-103

7. Cao, X., F. Yang, L. Ma, K.W. Wang, and J. Zheng. (2014) Divalent cations potentiate TRPV1 channel by lowering the heat activation threshold, Journal of General Physiology, 143(1): 75-90

8. Cui, Y., F. Yang, X. Cao, V. Yarov-Yarovoy, K.W. Wang, J. Zheng. (2012) Selective disruption of high-sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations, Journal of General Physiology, 139 (4)273-283. Featured on the cover

9. Cheng, W., F. Yang, S. Liu, C.K. Colton, C. Wang, Y. Cui, X. Cao, M.X. Zhu, C. Sun, K.W. Wang, and J. Zheng. (2012) Heteromeric Heat-Sensitive TRP Channels Exhibit Distinct Temperature and Chemical Response, Journal of Biological Chemistry, 287(10): 7279-7288

10. Yang, F., Y. Cui, K.W. Wang, and J. Zheng. (2010) Thermosensitive TRP channel outer pore is part of the temperature activation pathway, Proceedings of the National Academy of Sciences, 107:7083-7088.

11. Qu, Z., W. Cheng, Y. Cui, Y. Cui, and J. Zheng. (2009) Human disease-causing mutations disrupt an N-C terminal interaction and channel function of bestrophin 1, Journal of Biological Chemistry, 284:16473-16481.

12. Cheng, W., F. Yang, C.L. Takanishi, and J. Zheng. (2007) Thermosensitive TRPV Channel Subunits Co-assemble into Heteromeric Channels with Intermediate Conductance and Gating Properties, Journal of General Physiology, 129, 191-207.  13. Bykova, E.A., X.D. Zhang, T.Y. Chen, and J. Zheng. (2006) Large movement in the C terminus of CLC-0 chloride channel during slow gating, Nature Structural and Molecular Biology, 13, 1115-1119.

14. Zheng, J. and W.N. Zagotta. (2004) Stoichiometry and assembly of olfactory cyclic nucleotide-gated channels, Neuron, 42, 411-421.

Professor Michael A. Rogawski, M.D., Ph.D. Yale

Chair Emeritus, Department of Neurology

Director, Institute for Neurotherapeutics Discovery

Associate Director, UC Davis CounterACT Center of Excellence

School of Medicine

Dr. Rogawski is a leading international authority on the pathology and treatment of epilepsy and related neurological diseases.

Dr.Michael A. Rogawski from the Department of Neurology at the University of California, Davis School of Medicine was a member of the UC Davis Center for Neuroscience and the Pharmacology and Toxicology Graduate Group. Professor Michael A. Rogawski received a B.A. (biophysics) from Amherst College, and M.D. and Ph.D. (pharmacology) degrees from Yale University. I was a resident, fellow and assistant professor in the Department of Neurology at the Johns Hopkins University School of Medicine. For over 20 years, Professor Michael A. Rogawski was a senior investigator and chief of the Epilepsy Research Section at the National Institute of Neurological Disorders and Stroke.  His research interests involve ion channel pharmacology and neurological therapeutics, including antiepileptic drugs and other epilepsy treatment approaches. I am past president of the American Society for Experimental NeuroTherapeutics. [Electronic versions of publications are provided to ensure timely dissemination of academic work for noncommercial purposes. Copyright resides with the respective copyright holders as stated in each article.]

Selective Publications:

1. Broomall E, Natale JE, Grimason M, Goldstein J, Smith CM, Chang C, Kanes S, Rogawski MA, Wainwright MS. Pediatric super-refractory status epilepticus treated with allopregnanolone. Ann Neurol. 2014 Dec;76(6):911-5.

2. Fritsch B, Reis J, Gasior M, Kaminski RM, Rogawski MA. Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis. J Neurosci. 2014 Apr 23;34(17):5765-75.

3. Zolkowska D, Dhir A, Krishnan K, Covey DF, Rogawski MA. Anticonvulsant potencies of the enantiomers of the neurosteroids androsterone and etiocholanolone exceed those of the natural forms. Psychopharmacology (Berl). 2014 Sep;231(17):3325-32.

4. Wilcox KS, Dixon-Salazar T, Sills GJ, Ben-Menachem E, White HS, Porter RJ, Dichter MA, Moshé SL, Noebels JL, Privitera MD, Rogawski MA. Issues related to development of new antiseizure treatments. Epilepsia. 2013 Aug;54 Suppl 4:24-34.

5. Devinsky O, Vezzani A, Najjar S, De Lanerolle NC, Rogawski MA. Glia and epilepsy: excitability and inflammation. Trends Neurosci. 2013 Mar;36(3):174-84.

6. Porter RJ, Dhir A, Macdonald RL, Rogawski MA. Mechanisms of action of antiseizure drugs. Handb Clin Neurol. 2012;108:663-81.

7. French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, Kumar D, Rogawski MA. Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304. Neurology. 2012 Aug 7;79(6):589-96.

8. Rogawski MA, Federoff HJ. Disclosure of clinical trial results when product development is abandoned. Sci Transl Med. 2011 Sep 28;3(102):102cm29.

9. Fritsch B, Stott JJ, Joelle Donofrio J, Rogawski MA. Treatment of early and late kainic acid-induced status epilepticus with the noncompetitive AMPA receptor antagonist GYKI 52466. Epilepsia. 2010 Jan;51(1):108-17.

10. Rogawski MA, Suber P. Support for the NIH public access policy. Science. 2006 Sep 15;313(5793):1572.

11. Rogawski MA. Astrocytes get in the act in epilepsy. Nat Med. 2005 Sep;11(9):919-20.

12. Rogawski MA, Löscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci. 2004 Jul;5(7):553-64. Review.

13. Gryder DS, Rogawski MA. Selective antagonism of GluR5 kainate-receptor -mediated synaptic currents by topiramate in rat basolateral amygdala neurons. J Neurosci. 2003 Aug 6;23(18):7069-74.

14. Reddy DS, Rogawski MA. Stress-induced deoxycorticosterone-derived neurosteroids modulate GABA(A) receptor function and seizure susceptibility. J Neurosci. 2002 May 1;22(9):3795-805.