Rocco G. Gogliotti, Ph.D.
B.S. Biology, Eastern Michigan University, 2004
Ph.D. Biomedical Research, Northwestern University, 2012
Biosketch and Research Interests
Rocco Gogliotti joined the VCNDD in April of 2012. He completed his PhD at Northwestern University, where he did his thesis work on the pediatric neuromuscular disease Spinal Muscular Atrophy (SMA). Specifically, Rocco focused on defining where, when and how much rescue of the deficient survival motor neuron protein is required to correct the phenotype of mouse models of the SMA.
Rocco’s long-term research focus is pediatric diseases of the nervous system. Through a combination of genetic, behavioral and pharmacological methodologies, he seeks to better understand the disparities in nervous system function during health and disease, and to design novel intervention strategies to correct these deficits. Rocco’s work in the VNCDD has focused on the syndromic forms of autism, such as Rett syndrome and MECP2-Duplication syndrome, and the role that metabotropic glutamate receptors and muscarinic acetylcholine receptors play in disease etiology. These studies are rooted in expression data from the brains of human patients, where he has established that mGlu5, mGlu7 and M4 protein levels are significantly reduced. Using novel compounds developed in the VCNDD, he has defined which aspects of neurotransmission are affected by receptor deficiency, and identified specific symptom domains that can be rescued by normalizing their signaling pathways in model mice. The goal of these bench-to-bedside studies is to identify novel components of the basic science underlying disease, which are present in human patients and can be targeted therapeutically to improve the lives of the patients and families afflicted with these devastating disorders.
Gogliotti, R. G., Senter, R. K., Fisher, N. M., Adams, J., Zamorano, R., Walker, A. G., Blobaum, A. L., Engers, D. W., Hopkins, C. R., Daniels, J. S., Jones, C. K., Lindsley, C. W., Xiang, Z., Conn, P. J., and Niswender, C. M. (2017) mGlu7 potentiation rescues cognitive, social, and respiratory phenotypes in a mouse model of Rett syndrome. Science translational medicine 9
Fisher, N. M.*, Gogliotti, R. G.*, Vermudez, S. A. D., Stansley, B. J., Conn, P. J., and Niswender, C. M. (2017) Genetic reduction or negative modulation of mGlu7 does not impact anxiety and fear learning phenotypes in a mouse model of MECP2 Duplication syndrome. ACS chemical neuroscience.
*denotes co-first authorship
Abe, M.*, Seto, M.*, Gogliotti, R. G.*, Loch, M. T., Bollinger, K. A., Chang, S., Engelberg, E. M., Luscombe, V. B., Harp, J. M., Bubser, M., Engers, D. W., Jones, C. K., Rodriguez, A. L., Blobaum, A. L., Conn, P. J., Niswender, C. M., and Lindsley, C. W. (2017) Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a Series of Pyrazolo[1,5-a]pyrimidines. ACS medicinal chemistry letters 8, 1110-1115.
*denotes co-first authorship
Stansley, B. J., Fisher, N. M., Gogliotti, R. G., Lindsley, C. W., Conn, P. J., and Niswender, C. M. (2017) Contextual Fear Extinction Induces Hippocampal Metaplasticity Mediated by Metabotropic Glutamate Receptor 5. Cereb Cortex, 1-14
Gogliotti, R. G., Senter, R. K., Rook, J. M., Ghoshal, A., Zamorano, R., Malosh, C., Stauffer, S. R., Bridges, T. M., Bartolome, J. M., Daniels, J. S., Jones, C. K., Lindsley, C. W., Conn, P. J., and Niswender, C. M. (2016) mGlu5 positive allosteric modulation normalizes synaptic plasticity defects and motor phenotypes in a mouse model of Rett syndrome. Human molecular genetics 25, 1990-2004
Ponnazhagan, R., Harms, A. S., Thome, A. D., Jurkuvenaite, A., Gogliotti, R., Niswender, C. M., Conn, P. J., and Standaert, D. G. (2016) The Metabotropic Glutamate Receptor 4 Positive Allosteric Modulator ADX88178 Inhibits Inflammatory Responses in Primary Microglia. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 11, 231-237
Gogliotti, R. G., and Conn, P. J. (2016) Pharmacological Treatments for Autism Spectrum Disorder: Will Emerging Approaches Yield New Treatments? Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 41, 376-377
Gogliotti, R. G., Cardona, H., Singh, J., Bail, S., Emery, C., Kuntz, N., Jorgensen, M., Durens, M., Xia, B., Barlow, C., Heier, C. R., Plasterer, H. L., Jacques, V., Kiledjian, M., Jarecki, J., Rusche, J., and DiDonato, C. J. (2013) The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models. Human molecular genetics 22, 4084-4101
Gogliotti R.G., Heier, C., Barlow, Jorgensen, M., and DiDonato, C.J. (2012) Motor neuron rescue in spinal muscular atrophy mice demonstrates that sensory-motor defects are a consequence, not a cause, of motor neuron dysfunction. Journal of Neuroscience, Mar 14;32(11):3818-29.
Gogliotti R.G., Lutz K., Koh S., DiDonato C.J. (2011) Characterization of a commonly used mouse model of SMA reveals seizure susceptibility and diminished fear response. Neurobiology of Disease, Jul;43(1):142-51.
Kular R.K., Gogliotti R.G., Opal P. (2010) Cpd-1 null mice display subtle neurological phenotype. PLOS One, 5(9): e12649. doi:10.1371/journal.pone.0012649.
Hammond S., Gogliotti R.G., Rao V., Beauvais A., Kothary R., DiDonato C.J. (2010) Mouse survival motor neuron alleles that mimic SMN2 splicing and are inducible rescue embryonic lethality early in development but not late. PLOS One, 5(12):e15887.
Gogliotti R.G., Hammond S., Lutz K., DiDonato C.J. (2009) Molecular and phenotypic reassessment of an infrequently used model for spinal muscular atrophy. Biochemical Biophysical Research Communications, (391)517-522.
Gavrilina T., McGovern V., Workman E., Crawford T., Gogliotti R.G., DiDonato C.J., Monani U., Morris G., Burghes A. (2008) Neuronal SMN expression corrects spinal muscular atrophy in severe SMA mice while muscle-specific SMN expression has no phenotypic effect. Human and Molecular Genetics, 17(8) 1063-1075.
Heier C., Gogliotti R.G., DiDonato C.J. (2007) SMN Transcript Stability: Could Modulation of Messenger RNA Degradation Provide a Novel Therapy for Spinal Muscular Atrophy? Journal of Child Neurology. 22(8): 1013-8.2010
Wang X.; Gargalovic P.; Wong J.; Gu J.L.; Wu X; Qi H.; Wen P.; Xi L.; Tan B.; Gogliotti R.G.; L. W. C.; Chatterjee A.; Lusis A.J. (2004) Hyplip2, a New Gene for Combined Hyperlipidemia and Increased Atherosclerosis. Arteriosclerosis Thrombosis and Vascular Biology; 24(10):p.1928-34