Our laboratory seeks to understand mechanisms of neural circuit dysfunction in autism spectrum disorders (ASDs) and to develop new therapeutic approaches. We use behavioral, electrophysiological, biochemical, imaging and morphometric techniques in genetic mouse models of ASDs to define how perturbations in synaptic signaling alter normal behavior. A portion of our research program is dedicated to preclinical evaluation of novel therapeutics for Rett syndrome and other ASDs, with a particular focus on molecules that target TrkB and NMDA receptors. Under the auspices of the Autism Spectrum Research Consortium, directed by Dr. Katz, we also collaborate with clinical faculty here at Case Western Reserve University and elsewhere to foster human trials of potential new pharmacotherapies for ASDs.
Katz, D.M., Bird, A., Coenraads, M., Gray, S., Menon, D., Philpot, B.D., Tarquinio, D. (2016)
Rett Syndrome: Crossing the Threshold to Clinical Translation. Trends Neurosci. 2016 Feb;39(2):100-113. doi: 10.1016/j.tins.2015.12.008.
Sceniak, M.P., Lang, M., Enomoto, A.C., Howell, C., Hermes, D.J., Katz, D.M. (2015)
Mechanisms of Functional Hypoconnectivity in the Medial Prefrontal Cortex in Mecp2 Null Mice. Cereb Cortex. 2016 May;26(5):1938-1956. doi: 10.1093/cercor/bhv002. Epub 2015 Feb 7.
Kron, M., Adams, I., Lang, M., Longo, F. and D.M. Katz (2014)
A BDNF loop domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome. Disease Models & Mechanisms. 7(9):1047-55.
Katz, D.M. (2014)
"Brain derived neurotrophic factor and Rett syndrome in Neurotrophic Factors." Handbook of Experimental Pharmacology. G.R. Lewin and B.D. Carter, Eds.; 220:481-495 Springer-Verlag, Berlin.
Buchovecky, C.M., Brown, H.M., Huang, W., Coenraads, M., Crowe, J.K., Schrock, M.V., Probst, F.J., Katz, D.M., Shendure, J. and M.J. Justice (2013)
A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome. Nature Genetics. 45:1013-20.
Ogier, M., Kron, M. and Katz, D.M. (2013)
Neurotrophic factors in development and regulation of respiratory control. Compr. Physiol. 3:1125-34.
Katz DM, Berger-Sweeney JE, Eubanks JH, Justice MJ, Neul JL, Pozzo-Miller L, Blue ME, Christian D, Crawley JN, Giustetto M, Guy J, Howell CJ, Kron M, Nelson SB, Samaco RC, Schaevitz LR, (2012)
Preclinical research in Rett syndrome: Setting the foundation for translational success. Disease Models and Mechanisms. 5:733-45.
Kron, M., Howell, C. J., Adams, I.T., Ransbottom, M., Christian, D., Ogier, M. and D. M. Katz (2012)
Brain activity mapping in Mecp2 mutant mice reveals functionl deficits in forebrain circuits, including key nodes in the default mode network, that are reversed by ketamine treatment J. Neurosci. 32(40):13860-72.
Schmid, D., Yang, T., Ogier, M., Adams, I., Mirakhur, Y., Wang, Q., Massa, S., Longo, F. and D.M. Katz (2012)
A small molecule TrkB partial agonist rescues TrkB phosphorylation deficits and improves respiratory function in a mouse model of Rett syndrome.J. Neurosci. 32:1803-10.
Shepherd, G. and D.M. Katz (2011)
Synaptic microcircuit dysfunction in genetic models of neurodevelopmental disorders: focus on Mecp2 and Met. Current Opinion in Neurobiology. 21:827-33.
Clark, C.G., Hasser, E.M., Kunze, D.L., Katz, D.M. and D.D.Kline (2011)
Endogenous brain derived neurotrophic factor tonically regulates autonomic and synaptic function in the nucleus tractus solitarius.J. Neurosci. 31:12318-29.
Kline, D., Ogier, M., Kunze, D. and D.M. Katz (2010)
Exogenous brain derived neurotrophic factor rescues synaptic dysfunction in Mecp2 null mice J. Neurosci. 30:5303-10.
Taneja, P., Ogier, M., Brooks-Harris, G., Katz, D.M. and S. B. Nelson (2009)
Pathophysiology of locus coeruleus neurons in a mouse model of Rett Syndrome J. Neurosci. 29:12187-12195.
Katz, D.M., Dutschmann, M., Ramirez, N. and G. Hilaire (2009)
Breathing disorders in Rett Syndrome: Progressive neurochemical dysfunction in the respiratory network after birth Resp. Physiol. and Neurobiol. 168:101-8.
Bouvier, J., Autran, S., Dehorter, N., Katz, D.M., Champagnat, J., Fortin, G. and Thoby-Brisson, M. (2008)
Brain-derived neurotrophic factor enhances fetal respiratory rhythm frequency in the mouse preBötzinger complex in vitro. Eur J Neurosci. 2008 Aug;28(3):510-20. doi: 10.1111/j.1460-9568.2008.06345.x.
Ogier, M., Wang H., Hong, E., Wang, Q., Greenberg, M.E. and D. M. Katz. (2007)
Brain Derived Neurotrophic Factor and respiratory function improve after ampakine treatment in a mouse model of Rett Syndrome. J Neurosci. 27:10912-7.
Wang, H., Chan, S., Ogier, M., Hellard, D., Wang, Q., Smith, C. and D.M. Katz. (2006)
Dysregulation of BDNF expression and neurosecretion in MeCP2 null mice. J Neurosci. 26:10911-10915.
Wang, H., Yuan, G., Ward, N., Boswell, M. and D.M. Katz. (2006)
Secretion of brain derived neurotrophic factor from brain microvascular endothelial cells. Eur J Neurosci. 2006 Mar;23(6):1665-70.
Guo H, Hellard DT, Huang L, Katz DM. (2005)
Development of pontine noradrenergic A5 neurons requires brain-derived neurotrophic factor. Eur J Neurosci. 2005 Apr; 21(7):2019-2023.
Hellard D, Brosenitsch T, Fritzsch B, Katz DM. (2004)
Cranial sensory neuron development in the absence of brain-derived neurotrophic factor in BDNF/Bax double null mice. Dev Biol. 2004 Nov 1; 275(1):34-43.
Thoby-Brisson M, Cauli B, Champagnat J, Fortin G, Katz DM. (2003)
Expression of functional tyrosine kinase B receptors by rhythmically active respiratory neurons in the pre-Botzinger complex of neonatal mice. J Neurosci. 2003 Aug 20; 23(20):7685-7689.
Balkowiec A, Katz DM. (2002)
Cellular mechanisms regulating activity-dependent release of native brain-derived neurotrophic factor from hippocampal neurons. J Neurosci. 2002 Dec 1; 22(23):10399-10407.
Brosenitsch TA, Katz DM. (2002)
Expression of Phox2 transcription factors and induction of the dopaminergic phenotype in primary sensory neurons. Mol Cell Neurosci. 2002 Jul; 20(3):447-457.
Brosenitsch TA, Katz DM. (2001)
Physiological patterns of electrical stimulation can induce neuronal gene expression by activating N-type calcium channels. J Neurosci. 2001 Apr 15; 21(8):2571-2579.
Erickson JT, Brosenitsch TA, Katz DM. (2001)
Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor are required simultaneously for survival of dopaminergic primary sensory neurons in vivo. J Neurosci. 2001 Jan 15; 21(2):581-589.
Balkowiec A, Katz DM. (2000)
Activity-dependent release of endogenous brain-derived neurotrophic factor from primary sensory neurons detected by ELISA in situ. J Neurosci. 2000 Oct 1; 20(19):7417-7423.
Balkowiec A, Kunze DL, Katz DM. (2000)
Brain-derived neurotrophic factor acutely inhibits AMPA-mediated currents in developing sensory relay neurons. J Neurosci. 2000 Mar 1; 20(5):1904-1911.
Balkowiec A, Katz DM. (1998)
Brain-derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice. J Physiol. 1998 Jul 15; 510 ( Pt 2):527-533.
Katz DM, Balkowiec A. (1997)
New insights into the ontogeny of breathing from genetically engineered mice. Curr Opin Pulm Med. 1997 Nov; 3(6):433-439.
Erickson JT, Conover JC, Borday V, Champagnat J, Barbacid M, Yancopoulos G, Katz DM. (1996)
Mice lacking brain-derived neurotrophic factor exhibit visceral sensory neuron losses distinct from mice lacking NT4 and display a severe developmental deficit in control of breathing. J Neurosci. 1996 Sep 1; 16(17):5361-5371.
Conover JC, Erickson JT, Katz DM, Bianchi LM, Poueymirou WT, McClain J, Pan L, Helgren M, Ip NY, Boland P, et al.. (1995)
Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4. Nature. 1995 May 18; 375(6528):235-238.