Andrew J. Kennedy
Assistant Professor of Chemistry and Biochemistry
Chemistry and Biochemistry
Dana Chemistry Hall, Room 322
My research interest is to understand the chemical mechanisms that encode and maintain long-term memory. Currently, we investigate how learning imprints information onto the epigenome of participating neurons, and how these experientially-driven changes to the structure of the genome affect the expression of genes that facilitate plasticity. Using gene knockout models, antisense oligonucleotides, novel small molecules, and site-directed EpiTALEs, we probe the function of epigenetic modifying enzymes in and specific epigenetic markers of memory function. A major goal of our laboratory is to develop therapies that manipulate the epigenome to enhance cognition in cases of intellectual disability, such as Pitt-Hopkins Syndrome, and memory in Alzheimer’s disease.
1. Kristine E. Zengeler, Caroline P. Gettens, Hannah C. Smith, Mallory M. Caron, Xinyuan Zhang, Alexandra H. Howard, Andrea R. Boitnott, Alex R. Gogliettino, Anas Reda, Beth G. Malachowsky, Chun Zhong, Hongjun Song, Garrett A. Kaas, Andrew J. Kennedy. Tet2 negatively regulates memory fidelity. Submitted. https://www.biorxiv.org/content/10.1101/843581v1
2. Manjinder S. Cheema, Katrina V. Good, Bohyun Kim, Heddy Soufari, Connor O’Sullivan, Melissa E. Freeman, Gilda Stefanelli, Ciro Rivera Casas, Kristine E. Zengeler, Andrew J. Kennedy, Jose Maria Eirin Lopez, Perry L. Howard, Iva B. Zovkic, Jeffrey Shabanowitz, Deanna D. Dryhurst, Donald F. Hunt, Cameron D. Mackereth, and Juan Ausió. “Deciphering the Enigma of the Histone H2A.Z-1/H2A.Z-2 Isoforms: Novel Insights and Remaining Questions.” Cells. 2020, 9(5), 1167.
3. Shane G. Poplawski, Krassimira A. Garbett, Rebekah L. McMahan, Holly B. Kordasiewicz, Hien Zhao, Andrew J. Kennedy, Slavina B. Goleva, Teresa H. Sanders, S. Timothy Motley, Eric E. Swayze, David J. Ecker, J. David Sweatt, Todd P. Michael, Celeste B. Greer. “An antisense oligonucleotide leads to suppressed transcriptional elongation of Hdac2 and long-term memory enhancement.” Molecular Therapy-Nucleic Acids. 2020, 19, 1399-1412.
4. BaDoi N. Phan, Joseph F. Bohlen, Brittany A. Davis, Zengyou Ye, Huei-Ying Chen, Brent Mayfield, Srinidhi Rao Sripathy, Stephanie Cerceo Page, Morganne N. Campbell, Hannah L. Smith, Danisha Gallop, Hyojin Kim, Courtney L. Thaxton, Jeremy M. Simon, Emily E. Burke, Joo Heon Shin, Andrew J. Kennedy, J. David Sweatt, Benjamin D. Philpot, Andrew E. Jaffe, and Brady J. Maher. “A myelin-related transcriptomic profile is shared by Pitt–Hopkins syndrome models and human autism spectrum disorder.” Nature Neuroscience. 2020, 23, 375–385.
5. Gabriella N. L. Chua, Kelly L. Wassarman, Haoyu Sun, Joseph A. Alp, Emma I. Jarczyk, Nathanael J. Kuzio, Michael J. Bennett, Beth G. Malachowsky, Martin Kruse, Andrew J. Kennedy. “Cytosine-based TET Enzyme Inhibitors.” ACS Medicinal Chemistry Letters. 2019, 10(2):180-185.
6. Gilda Stefanelli, Amber B. Azam, Brandon J. Walters, Mark A. Brimble, Caroline P. Gettens, Pascale Bouchard-Cannon, Hai-Ying M. Cheng, Andrew M. Davidoff, Klotilda Narkaj, Jeremy J. Day, Andrew J. Kennedy, and Iva B. Zovkic. “Learning and age-related changes in genome-wide H2A.Z binding in the mouse hippocampus.” Cell Reports. 2018, Jan 30;22(5):1124-1131.
7. Katie L Bales, Lara Ianov, Andrew J Kennedy, J David Sweatt, Alecia K Gross. “Autosomal dominant retinitis pigmentosa rhodopsin mutant Q344X drives specific alterations in chromatin complex gene transcription.” Molecular Vision. 2018, 24, 153-164.
8. Alex R. Gogliettino and Andrew J. Kennedy. “Transcription Factor 4.” Encyclopedia of Signaling Molecules, Second Edition. 2018. doi: 10.1007/978-1-4614-6438-9_101934-1
9. Lara Ianov, Matt De Both, Monica Chawla, Asha Rani, Andrew J. Kennedy, Ignazio Piraz, Jeremy J Day, Ashley Siniard, Ashok Kumar, J. David Sweatt, Carol A Barnes, Matthew J Huentelman, Thomas C Foster. “Hippocampal transcriptomic profiles: Subfield vulnerability to age and cognitive impairment.” Frontiers in Aging Neuroscience. 2017, 9, 383.
10. Corey G. Duke, Andrew J. Kennedy, Cristin F. Gavin, Jeremy J. Day, & J. David Sweatt. “Experience-dependent epigenomic reorganization in the hippocampus.” Learning and Memory. 2017, 24(7), 278-288.
11. Andrew J. Kennedy, Elizabeth J. Rahn, Brynna S. Paulukaitis, Holly B. Kordasiewicz, Jing Wang, John W. Lewis, Jessica P. Watson, Sarah K. Strange, Mikael C. Guzman-Karlsson, Scott E. Phillips, S. Timothy Motley, Eric E. Swayze, David J. Ecker, Jeremy J. Day, Todd P. Michael, and J. David Sweatt. “Tcf4 regulates synaptic plasticity, DNA methylation, and memory function.” Cell Reports. 2016, 16 (10), 2666-2685.
12. Andrew J. Kennedy, Alexandra Bruce, Catherine Gineste, Thomas E. Ballard, Igor Olekhnovich, Timothy L. Macdonald, and Paul Hoffman. “Synthesis and Antimicrobial Evaluation of Amixicile-Based Inhibitors of the Pyruvate: Ferredoxin Oxidoreductases of Anaerobic Bacteria and Epsilon Proteobacteria.” Antimicrobial Agents and Chemotherapy. 2016, AAC. 00670-16.
13. Andrew J. Kennedy and J. David Sweatt. “Drugging the methylome: DNA methylation and memory.” Crit Rev Biochem Mol Biol. 2016, Feb 25:1-10.
14. Joseph D. Houck, Thomas K. Dawson, Andrew J. Kennedy, Yugesh Kharel, Niels D. Naimon, Saundra D. Field, Kevin R. Lynch, Timothy L. Macdonald. “Structural requirements and docking analysis of amidine-based sphingosine kinase 1 inhibitors containing oxadiazoles.” J. Med. Chem. Let. 2016, 7 (5), pp 487–492.
15. Jeremy J. Day*, Andrew J. Kennedy*, J. David Sweatt. “DNA methylation and its implication and accessibility for neuropsychiatric therapeutics.” Annual Review of Pharmacology and Toxicology. 2015, 55:591-611.
16. Vladimir Grubišić, Andrew J. Kennedy, J. David Sweatt and Vladimir Parpura. “Pitt-Hopkins mouse model has altered particular gastrointestinal transits in vivo.” Autism Research. 2015, Feb 26.
17. Dinesh Kumar, Milan Aggarwal, Garrett A. Kaas, John Lewis, Jing Wang, Daniel L. Ross, Chun Zhong, Andrew J. Kennedy, Hongjun Song and J. David Sweatt. “Tet1 Oxidase Regulates Neuronal Gene Transcription, Active DNA Hydroxy-methylation, Object Location Memory, and Threat Recognition Memory.” Neuroepigenetics. 2015, Oct 1;4:12-27
18. James E. East*, Andrew J. Kennedy*, Tonya J. Webb. “Raising the roof: The preferential pharmacological stimulation of Th1 and Th2 responses mediated by NKT cells.” Medical Research Reviews. 2014, Jan;34(1):45-76.
19. Cirle A. Warren, Edward van Opstal, T. Eric Ballard, Andrew J. Kennedy, Xia Wang, Mary Riggins, Igor Olekhnovich, Michelle Warthan, Glynis L. Kolling, Richard L. Guerrant1, Timothy L. Macdonald, and Paul S. Hoffman. “Amixicile: A Novel Inhibitor of Pyruvate: Ferredoxin Oxidoreductase with Improved Bioavailability and Efficacy against Clostridium difficile in a Mouse Infection Model” Antimicrobial Agents and Chemotherapy. 2012, 56(8), 4103-11.
20. Andrew J. Kennedy, Thomas P. Mathews, Yugesh Kharel, Saundra D. Field, Morgan L. Moyer, James E. East, Joseph D. Houck, Kevin R. Lynch, and Timothy L. Macdonald. “Development of Amidine-Based Sphingosine Kinase 1 Nanomolar Inhibitors and Reduction of Sphingosine 1-Phosphate in Human Leukemia Cells” J. Med. Chem. 2011, 54, 3524-3548.
21. Yugesh, Kharel, Thomas P. Mathews, Andrew J. Kennedy, Joseph D. Houck, Timothy L. Macdonald, Kevin R. Lynch. “A rapid assay for the assessment of sphingosine kinase inhibitors and substrates” Anal. Biochem. 2011, 411, 230-235.
22. Thomas P. Mathews, Andrew J. Kennedy, Yugesh Kharel, Perry C. Kennedy, Oana Nicoara, Manjula Sunkara, Andrew J. Morris, Brain Wamhoff, Kevin Lynch, Timothy L. Macdonald. “Discovery, Biological Evaluation and Structure-Activity Relationship of Amidine-Based Sphingosine Kinase Inhibitors.” J. Med. Chem. 2010, 53, 2766-2778.
23. James E. East, Andrew J. Kennedy, Jose L. Tomsig, Alexandra R. De Leon, Kevin R. Lynch, Timothy L. Macdonald. “Synthesis and structure-activity relationships of tyrosine-based inhibitors of autotaxin (ATX)” Bioorg. Med. Chem. Let. 2010, 20, 7132-7136.