Pharmacology and Toxicology - Research

Fernanda Laezza, M.D., Ph.D.

Assistant Professor


Research Interests

The research in our laboratory is directed at understanding the cellular and molecular mechanisms underlying modulation of ion channels in relationship to intrinsic excitability, synaptic transmission and plasticity. Rapid progress in the complementary fields of molecular genetics and cellular electrophysiology has lead to the appreciation of mechanistic links between ion channel dysfunction, long-term alterations in neuronal activity and the phenotypic expression of a variety of neurological disorders. Hence, ion channels have become a promising and attractive target for drug discovery and for the development of new therapeutic treatments against human diseases. Our major effort is currently focused at understanding the physiological activity of the intracellular fibroblast growth factors (iFGFs), a set of four genes (FGF11-14) abundantly expressed in neurons of the central and peripheral nervous systems.

Selected Publications

F. Laezza, A. Lampert, MA. Kozel, BR. Gerber, AM. Rush, JM. Nerbonne, SG. Waxman, SD. Dib-Hajj, DM. Ornitz. FGF14 N-terminal splice variants differentially modulate Nav1.2 and Nav1.6-encoded sodium channels. Mol Cell Neurosci. 2009.

R. Goetz, K. Dover, F. Laezza, N. Shtraizent, X. Huang, D. Tchetchik, AV. Eliseenkova, CF. Xu, TA. Neubert, DM. Ornitz, M. Goldfarb, M. Mohammadi. Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a conserved surface on FHFs for binding and modulation of voltage-gated sodium channels. J Biol Chem. 2009 284(26):17883-96.

F. Laezza, T. Wilding, S. Sequeira, AM Craig and JE. Huettner. The BTB/kelch protein, KRIP6, modulates the interaction of PICK1 with GluR6 kainate receptors, Neuropharmacology, 2008 55(7):1131-9

F. Laezza, Lou JY Gerber BR, Kozel M, Hartman H, Craig AM, Ornitz DM, Nerbonne JM. The FGF14F145S mutation disrupts the interaction of FGF14 with voltage-gated Na+ and impairs neuronal excitability, Journal of Neuroscience, 2007 27(44):12033-12044.

F. Laezza, Wilding TJ, Sequeira S, Coussen F, Zhang XZ, Hill-Robinson R, Mulle C, Huettner JE, Craig AM. KRIP6: a novel BTB/kelch neuronal protein modulates kainate receptors, Mol Cell Neurosci., 2007 (4):539-50.

M. Xiao, L. Xu, F. Laezza, K. Yamada, S. Feng and DM. Ornitz. Impaired hippocampal synaptic transmission and plasticity in mice lacking fibroblast growth factor 14 Mol Cell Neurosci., 2007 (3):366-77.

Lou JY, F. Laezza, Gerber BR, Xiao M, Yamada KA, Hartmann H, Craig AM, Nerbonne JM, Ornitz DM. Fibroblast Growth Factor 14 is an Intracellular Modulator of Voltage-Gated Sodium Channels Journal of Physiology, 2005 (569):179-93.

F. Laezza and R. Dingledine Voltage controlled plasticity at GluR2-deficient synapses onto hippocampal interneurons J Neurophysiol., 2004 (6):3575-81.

F. Laezza, J. J Doherty and R. Dingledine Long-term depression in hippocampal interneurons: joint requirement for pre and postsynaptic events. Science, 1999 (285): 1411-1414.

Distasi C, Munaron L, F. Laezza, Lovisolo D Basic fibroblast growth factor opens calcium-permeable channels in quail mesencephalic neural crest neurons. Eur J Neurosci. (1995) 516-20.

Laezza, F., Doherty, J.J. and Dingledine, R. Long-term depression in hippocampal interneurons: joint requirement for pre and postsynaptic events. Science, 285: 1411-1414, 1999.

Laezza, F. and Dingledine, R. Voltage controlled plasticity at GluR2-deficient synapses onto hippocampal interneurons J Neurophysiol, 6:3575-3581, 2004.

Lou, J.Y., Laezza, F., Gerber, B.R., Xiao, M., Yamada, K.A., Hartmann, H, Craig, A.M., Nerbonne, J.M. and Ornitz, D.M. Fibroblast Growth Factor 14 is an Intracellular Modulator of Voltage-Gated Sodium Channels. Journal of Physiology, 569:179-193, 2005.

Xiao, M., Xu, L., Laezza, F., Yamada, K.A., Feng, S. and Ornitz, D.M. Impaired hippocampal synaptic transmission and plasticity in mice lacking fibroblast growth factor 14. Mol Cell Neurosci, 3:366-377, 2007.

Laezza, F., Wilding, T.J., Sequeira, S., Coussen, F., Zhang, X.Z., Hill-Robinson, R., Mulle, C., Huettner, J.E. and Craig, A.M. KRIP6: a novel BTB/kelch neuronal protein modulates kainate receptors, Mol Cell Neurosci, 4:539-550, 2007. PMCID: PMC1939939.

Laezza, F., Gerber, B.R., Lou, J.Y., Kozel, M., Hartman, H., Craig, A.M., Ornitz, D.M., and Nerbonne, J.M. The FGF14F145S mutation disrupts the interaction of FGF14 with voltage-gated Na+ and impairs neuronal excitability. J Neurosci, 27:12033-12044, 2007. PMCID: PMC1464207

Laezza, F., Wilding, T., Sequeira, S., Craig, A.M. and Huettner, J.E. The BTB/kelch protein, KRIP6, modulates the interaction of PICK1 with GluR6 kainate receptors, Neuropharmacology, 55:1131-1139, 2008. PMCID: PMC2685165.

Goetz, R., Dover, K., Laezza, F., Shtraizent, N., Huang, X., Tchetchik, D., Eliseenkova, A.V., Xu, C.F., Neubert, T.A., Ornitz, D.M., Goldfarb, M. and Mohammadi, M. Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a conserved surface on FHFS for binding and modulation of voltage-gated sodium channels. J Biol Chem. 284:17883-17896, 2009. PMCID: PMC2719427.

Laezza, F., Lampert, A., Kozel, M.A., Gerber, B.R., Rush, A.M., Nerbonne, J.M., Waxman, S.G., Dib-Hajj, S.D and Ornitz, D.M. FGF14 n-terminal splice variants differentially modulate Nav1.2 and Nav1.6-encoded sodium channels. Mol Cell Neurosci, 42:90-101, 2009. PMCID: PMC2832592

Laezza, F., and R. Dingledine. Induction and expression rules of synaptic plasticity in hippocampal interneurons. Neuropharmacology, 60:720-9, 2011.

Reese, L.C., Laezza, F., Woltjer, R.,Taglialatela, G. Dysregulated phosphorylation of Ca2+/calmodulin dependent protein kinase II in the hippocampus of subjects with mild cognitive impairment and Alzheimer's disease. J Neurochem 119, 791-804, 2011.

Shavkunov, A., Panova, N., Prasai, A.,Veselenak, R., Bourne, N., Stoilova-McPhie, S.,Laezza, F. Bioluminescence methodology for the detection of protein:protein interactions within the voltage-gated sodium channel macromolecular complex Assay Drug Dev Technol. (2012; in press; DOI: 10.1089/adt.2011.0413).

Laezza, F. An interview with Fernanda Laezza, M.D., Ph.D., Department of Pharmacology and Toxicology, UTMB, Galveston, TX: interviewed by Vicki Glaser. Assay Drug Dev Technol. (2012; in press; DOI:10.1089/adt.2012.1001.pr).

Hernandez-Herrera, P., Jimenez, D., Kakadiaris, AI., Koustogiannis, A., Labate, D., Laezza, F., Papadakis, M. A harmonic analysis view of neuroscience imaging. To appear in Applied and Numerical Harmonic Analysis, Editor: Benedetto, J., Springer-Birkhauser press 2012.