|Name:||Michy P. Kelly, Ph.D.|
|Department:||Pharmacology, Physiology, & Neuroscience|
Postdoctoral: University of Pennsylvania|
Ph.D: Wake Forest University School of Medicine
BS: Towson University
How is it our brains—tangible entities—are able to store memories of intangible sights, sounds, emotions and ideas? What draws you toward one person, but repels you from another? My lab tries to answer these questions. Specifically, we explore how cyclic nucleotide signaling controls the formation of social memories and social interactions, and how alterations in this cascade might contribute to social deficits that are seen in patients with neurodevelopmental, psychiatric, and age-related disease. To do this, we identify molecular changes in tissue from patients and then mimic those changes in rodents in order to determine their behavioral, biochemical, and molecular consequences. We also use in vitro approaches to determine how mutations may change enzymatic activity or the subcellular compartmentalization of enzymes. Studies are conducted during development, early adulthood, and late adulthood in order to understand factors that modulate resiliency of the brain as well as those that trigger the manifestation of neurocognitive deficits later in life.
Our ultimate hope is that an improved understanding of the molecular mechanisms of social memory formation and social interactions will lead to the development of novel therapeutics for neurodevelopmental, psychiatric, and/or age-related diseases where these social behaviors are compromised.
FIGURE: Phosphodiesterase 11A4 (PDE11A4) is the only phosphodiesterase whose expression in brain is restricted to the hippocampal formation. This restricted expression pattern makes PDE11A4 a highly intriguing therapeutic target for neurodevelopmental, psychiatric and age-related disorders. Consistent with the fact that PDE11A4 is enriched in the ventral hippocampus, a brain region important in the regulation of mood and social behaviors, we have shown that decreasing PDE11A4 impairs the ability to form social memories, alters social interactions, and increases efficacy of the mood stabilizer lithium. DHIPP—dorsal hippocampus; VHIPP—ventral hippocampus.
- Pathak G, Agostino MJ, Bishara K, Capell WR, Fisher JL, Hegde S, Ibrahim BA, Pilarzyk K, Sabin C, Tuczkewycz T, Wilson S, and Kelly MP* (in press) PDE11A Negatively Regulates Lithium Responsivity. Molecular Psychiatry. Epub ahead of print DOI: MP.2016.155
- Salpietro V, Nakashima K, Kimura H, Efthymiou S, Manole A, Di Rosa G, Wiethoff S, Bettencourt C, Vandrovoca J, Chelban V, Raskind W, Bello OD, Kelly MP, Perez-Dueñas B, Davies CH, Macaya A, Houlden H. (accepted pending minor revisions) Homozygous mutation in PDE2A causes a hereditary chorea with onset in early infancy. Movement Disorders.
- Kelly MP* (2017) A role for Phosphodiestearse 11A (PDE11A) in the formation of social memories and the stabilization of mood. Advances in Neurobiology. 17:201-230. [Invited book chapter]
- Kelly MP* (2016) Phosphodiesterase 11A. Choi S, ed. Encyclopedia of Signaling Molecules. Springer, Inc. DOI 10.1007/978-1-4614-6438-9_101747-1 [Invited book chapter]
- Hegde S, Capell WR, Ibrahim BA, Klett J, Patel NS, Sougiannis AT, and Kelly MP* (2016) Phosphodiesterase 11A (PDE11A), enriched in ventral hippocampus neurons, is required for the consolidation of social but not non-social memories in mice. Neuropsychopharmacology. 41(12):2920-2931.
- Hegde S, Hao J, Oliver D, Patel NS, Poupore N, Shtutman M, Kelly MP* (2016) PDE11A regulates social behaviors and is a key mechanism by which social experience sculpts the brain. Neuroscience. 335:151-169.
- Pathak G, Ibrahim BA, McCarthy SM, Baker K, and Kelly MP* (2015) Amphetamine sensitization in mice is sufficient to produce both manic- and depressive-related behaviors as well as changes in the functional connectivity of corticolimbic structures. Neuropharmacology. 95:434-447.
- Kelly MP* (2015) Does Phosphodiesterase 11A (PDE11A) Hold Promise as a Future Therapeutic Target? Current Pharmaceutical Design. 21(3):389-416. [Invited Review].
- Kelly MP*, Adamowicz W, Bove S, Hartman AJ, Mariga A, Pathak G, Reinhart V, Romegialli A, and Kleiman RJ (2014) Select 3’,5’-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain. Cellular Signalling. 26:383-397.
- Kelly MP* (2014) Putting together the pieces of phosphodiesterase distribution patterns in the brain: A jigsaw puzzle of cyclic nucleotide regulation. Chapter 2 In Brandon NJ & West A, eds. Cyclic Nucleotide Phosphodiesterases in the Central Nervous System: From Biology to Disease. John Wiley & Sons, Inc. [Invited book chapter].
A full list of publications can bee seen here: http://www.ncbi.nlm.nih.gov/sites/myncbi/michy.kelly.1/bibliography/47781448/public/?sort=date&direction=ascending
Katy Pilarzyk—graduate student
Jennifer Klett—undergraduate student
Alvina Emran—undergraduate student
Neema Patel—research specialist
Latarsha Porcher—research specialist
Abigail Smith—research specialist