Update Your ProfileAcademic Title:
Associate Professor
Primary Appointment:
Neurobiology
Location:
685 W. Baltimore Street, HSFI 280I
Phone (Primary):
667-900-8704
Education and Training
- Towson State University, BS (Double Major: Theatre and Psychology), Summa Cum Laude, 1992
- Wake Forest University, PhD (Neuroscience), 2002
- University of Pennsylvania, Postdoctoral Fellowship (Neuroscience), 2002-2006
Biosketch
A keen interest in the molecular mechanisms of learning and memory is what originally drove me to become a neuroscientist, and a desire to identify novel therapeutic targets for age-related disorders and neuropsychiatric diseases is what keeps me invested. My lab takes an integrative approach. We first identify genetic, molecular or biochemical changes that are associated with aging or disease in humans and then use animal models to explore how those perturbations affect brain biochemistry and behavior. We also use in vitro approaches to identify intramolecular signals that control the catalytic activity or the subcellular compartmentalization of an enzyme. In so doing, we are able to identify novel mechanisms by which we can therapeutically manipulate enzyme function.
More specifically, we explore how cyclic nucleotide signaling controls the formation of social memories and social interactions. In particular, my lab focuses on the superfamily of enzymes that degrade cyclic nucleotides known as phosphodiesterases (PDEs), and I am considered a leading world expert in this field. Studies in animals 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 how PDEs regulate social memory formation and social interactions will lead to the development of novel therapeutics for diseases where these social behaviors are compromised. Our integrative approach has led us to therapeutically target the enzyme PDE11A using both small molecules and biologics, both of which we are now testing in preclinical models of age-related cognitive decline.
Follow us on Twitter: @KickassKe11yLab
Highlighted Publications
Pilarzyk K, Capell WR, Porcher L, Rips-Goodwin A, Kelly MP* (2023) Biologic that disrupts PDE11A4 homodimerization in hippocampus CA1 reverses age-related cognitive decline of social memories in mice. Neurobiology of Aging. 131:39-51. doi.org/10.1016/j.neurobiolaging.2023.07.008 [previously: bioRxiv https://biorxiv.org/cgi/content/short/2022.08.31.506102v1]
Pilarzyk K, Porcher L, Capell WR, Burbano S, Fisher JL, Gorny N, Petrolle S, Kelly MP* (2022) Conserved age-related increases in hippocampal PDE11A4 cause unexpected proteinopathies and cognitive decline of associative social memories. Aging Cell. 12(10):e13687. doi.org/10.1111/acel.13687. (previously: bioRxiv. doi: https://doi.org/10.1101/2022.04.08.487696) PMID: 36073342; PMCID: PMC9577960. [Featured on University of Maryland School of Medicine landing page and Maryland Medicine Front Line News, the Quantum Photonics Podcast, and 28+web outlets from more than 11 countries (Indonesia, France, Turkey, Australia, UK, India, Italy, US, Russia, Canada, Venezuela and more) including Cosmos Magazine, Medium.com, ALZFORUM, simonsfoundation.org, VerveTimes Mirage News, Scienmag, Science Daily.com, NeuroscienceNews.com, mind.help, headtopics.com, diariodasaude.com.br, neuroexpert.org, Alzheimer-riese.it, tenemosnoticias.com., Technology Networks, LENTA.RU, Nachrichten Welt, MedIndia etc.]
Smith A, Farmer R, Pilarzyk K, Porcher L, Kelly MP* (2021). A genetic basis for friendship? Homophily for membrane-associated PDE11A-cAMP-CREB signaling in CA1 of hippocampus dictates mutual social preference in male and female mice. Molecular Psychiatry. 26:7107-7117. Epub ahead of print. DOI: 10.1038/s41380-021-01237-4. [Featured on the University of Maryland School of Medicine landing page, Maryland Medicine Front Line News, Dean Reece’s State of the School Address as well as in the following: New York Post, LabRoots, Laboratory Equipment, Science Connected Magazine, NBC Washington WRC-TV and 6 other local TV stations across the country, WTOP-DC radio and 7 other local radio stations across the country, as well 24 web outlets in 6 different countries (e.g., News-Medical.net (UK), ScienceDaily, Technology Networks (UK), Neuroscience News Online, U.S.A.NewsWall.com, techilive.com (India), Times of News (India), NewsCaf (Canada), MedicallyPrime.com, Science Newsnet, Medical Xpress, Newswise, Mirage News Australia, Mirage News Australia, Poinformowani.pl (Poland), EurekaAlert.org, etc.]
Porcher L, Bruckmeier S, Burbano SD, Finnell JE, Gorny N, Klett J, Wood SK, Kelly MP* (2021) Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions. Journal of Neuroinflammation.
Farmer R, Burbano SD, Patel NS, Sarmiento A, Smith AJ, and Kelly MP* (2020) Phosphodiesterases PDE2A and PDE10A both change mRNA expression in the human brain with age, but only PDE2A changes in a region-specific manner with psychiatric disease Cellular Signalling. 70: article 109592. doi.org/10.1016/j.cellsig.2020.109592.
Baillie G, Tejeda G, and Kelly MP* (2019) Therapeutic targeting of 3’,5’-cyclic nucleotide phosphodiesterases: Inhibition and beyond. Nature Reviews Drug Discovery. 18(10):770-796. DOI : 10.1038/s41573-019-0033-4 [Peer-reviewed Invited Review]
Pilarzyk K, Klett J, Pena E, Porcher L, Smith AJ, Kelly MP* (2019) Loss of function of phosphodiesterase 11A shows recent and remote long-term memory can be uncoupled. Current Biology. 29:2307-2321. https://doi.org/10.1016/j.cub.2019.06.018
Patel NS, Klett J, Pilarzyk K, Lee D, Kass D, Menniti F, Kelly MP* (2018) Identification of new phosphodiesterase 9A (PDE9A) isoforms and how their expression and subcellular compartmentalization in brain changes across the lifespan. Neurobiology of Aging. 65:217-234.
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* (2017) PDE11A Negatively Regulates Lithium Responsivity. Molecular Psychiatry. 22(12):1714-1724.
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 Consolidation of Social but not Nonsocial 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.
Awards and Affiliations
2008 Leadership at the Bench, Wyeth
2008 Named as Editorial Board Member, Signal Transduction Insights
2009 Leadership at the Bench, Wyeth
2010 Individual Performance Award, Pfizer—Excellence in publishing
2011 Individual Performance Award, Pfizer—Excellence in mentoring
2011 Individual Performance Award, Pfizer—Excellence in training
2015 Elected to Faculty Senate, University of South Carolina
2015 Featured Scholar, University of South Carolina
2015 NARSAD Young Investigator Award, Brain & Behavior Research Foundation
2016 Breakthrough Star Award, University of South Carolina
2016 Distinguished Undergraduate Research Mentor of the Year, University of South Carolina
2018 Visiting Professor of Hong Hui Hospital and Xi’an Jiaotong University in Xi’an, China
2018 Distinguished Research Service Award, University of South Carolina (1st year award issued)
2018 Elected Future Chair of Gordon Research Conference on Cyclic Nucleotide Phosphodiesterases
2018-present Editorial Board Member, Cellular Signalling (an Elsevier Journal)
2019 Accepted into the Veterans Affairs Intramural Program for Non-Clinician Scientists
2021 Nominee, Bernice Grafstein Award for Outstanding Accomplishments in Mentoring
2022 Member, PhrMA Foundation Drug Discovery Study Section
2022 Elected Representative, University of Maryland School of Medicine Council
2022 Member, Scientific Advisory Board for Surveyor Sciences
2023 Selected mentor for the CURE Neuroscience Scholars Program
2023 Selected for the University of Pittsburgh TRANSFORM Leadership Program
2023-2026 Re-elected Representative, University of Maryland School of Medicine Council
2023-2026 Elected Faculty Senator, University of Maryland, Baltimore
Grants and Contracts
2022-2023 NIA 3R01AG061200-05S2 “Role of Cyclic Nucleotide Signaling in Age-related Decline of Social Memories Loss Supplement” ($234,094 total costs for 1 year; P.I., MP Kelly)
2022-2023 NIA 3R01AG061200-05S1 “Functional effects of PDE11A Alzheimer’s-associated variants” ($386,171 total costs for 1 year; P.I., MP Kelly)
2020-2025 NIA R01AG067836 “Pharmacological inhibitors of PDE11A for treatment of age-related cognitive decline”($3,559,864 total costs over 5 years; coP.I.s MP Kelly, Charlie Hoffman, & David Rotella2019-2024 NIA R01AG061200 NIA “Role of Cyclic Nucleotide Signaling in Age-related Decline of Social Memories” ($2,381,960 total costs over 5 years; P.I., MP Kelly)
2017-2020 NIA R01AG054839, “Brain targeted nanoparticle for Alzheimer’s disease therapy” ($1,250,000 direct costs over 5 years; PI, Xu P; Co-I, Kelly MP)
2017-2018 University of South Carolina ASPIRE III Grant. “Acquisition of Logos X-ClarityTM Tissue Clearing System and Confocal Microscopy Objective for the USC Instrumentation Resource Facility” ($64,390; PI Price B; Co-I Kelly MP)
2015-2017 Brain and Behavior Research Foundation NARSAD Young Investigator Grant, “Dissecting the molecular and anatomical pathways of recent versus remote long-term memory” ($65,000 over 2 years; P.I., MP Kelly)
2014-2019 NIMH R01MH101130, “Compartmentalization of cyclic nucleotide signaling in the ventral hippocampus” ($1,250,000 direct costs over 5 years; P.I., MP Kelly)
2014-2019 NIGMS P20GM109091-01 COBRE Center, “Targeted Therapeutics” ($11.3 million direct costs over years; P.I. Igor Roninson). Project 3, “Selective Targeting of PDE11A4 transcription and catalytic activity” (original award $450,000 over 3 years direct costs, reduced to $50,000 for 1 year upon receipt of R01; Project 3 P.I., MP Kelly)
2014 University of South Carolina ASPIRE I Grant, “Dissecting the molecular and anatomical pathways of recent versus remote long-term memory” ($15,000 for 16 months; P.I., MP Kelly)
2013 University of South Carolina School of Medicine Research Development Fund Grant, “Identifying When and Where PDE11A Compartmentalizes Cyclic Nucleotides in Brain” ($15,000 for 1 year; P.I., MP Kelly)
2013 University of South Carolina ASPIRE I Grant, “Intramolecular Signals Controlling Phosphodiesterase 11A (PDE11A) Function in Brain” ($15,000 for 16 months; P.I., MP Kelly)
2013 PhRMA Research Starter Grant in Pharmacology/Toxicology*, “Compartmentalization of Cyclic Nucleotides in the Ventral Hippocampus” ($60,000 for 1 year; P.I., MP Kelly) *1 of only 2 awarded nationally.2007
2009 NARSAD Young Investigator Award, “Using MRI in an endophenotypic mouse model of schizophrenia to identify the developmental vs degenerative origins of neuroanatomical changes and their relationship toneurocognitive deficits” ($60,000; P.I., MP Kelly—award monies not accepted due to affiliation with Wyeth Research at time of award announcement)
2006 Tourette Syndrome Association Research Award, Competitive renewal, “The role of intracellular signaling pathways in endophenotypes of Tourette’s Syndrome” ($40,000; P.I., MP Kelly)
2005 Tourette Syndrome Association Research Award, “The role of intracellular signaling pathways in endophenotypes of Tourette’s Syndrome” ($40,000; P.I., MP Kelly)
Previous Positions
- 2006-2009 Senior Research Scientist II, Wyeth Research, Princeton, NJ
- 2009-2011 Principal Scientist, Pfizer, Groton, CT (company change due to Pfizer’s purchase of Wyeth)
- 2012-2018 Tenure Track Assistant Professor, University of South Carolina School of Medicine, Columbia, SC
- 2018-2021 Associate Professor with tenure, University of South Carolina School of Medicine, Columbia, SC
Mentored Awards
2023 Astronaut Scholarship ($15,000; student: Audrey Rips-Goodwin; co-mentor: MPKelly)
2022 University of Kansas Nominee for Goldwater Scholarship (student: Audrey Rips-Goodwin; co-mentor: MPKelly)
2022 Diversity Supplement for DA022340 Endogenous cannabinoid control of reward substrates (student: Antonio Figueiredo; PI and mentor, JFCheer; co-mentor: MPKelly)
2022 Louis Stokes Alliance for Minority Participation Research Fellow (student: Preethi Badugu; mentor: MPKelly)
2021 Abstract selected for talk slot, “Aging Induces Asymmetric Trafficking of PDE11A4 in the Ventral Hippocampus”. Baltimore Brain Series (student: Sophie Bruckmeier; mentor: MPKelly)
2021 Geriatrics and Gerontology Education and Research Program Basic Science Award at the University of Maryland, Baltimore Graduate Research Conference (student: Sophie Bruckmeier; mentor: MPKelly)
2021 UofSC Dean C. Barnhardt Award for outstanding service (student: Katy Pilarzyk; mentor: MPKelly)
2021 First Place, W. Morgan Newton Graduate Research Symposium (student: Katy Pilarzyk; mentor: MPKelly)
2021 UofSC Biomedical Graduate Student Association President’s Award for service (student: Katy Pilarzyk; mentor: MPKelly)
2020 University of South Carolina Breakthrough Graduate Scholar Award (student: Katy Pilarzyk; mentor: MPKelly)
2019 National Science Foundation Graduate Research Fellowship ($138,000; P.I. Katy Pilarzyk; mentor: MPKelly)
2019 Winner Best Poster, “PDE2A mRNA expression is altered in select brain regions of patients with major depressive disorder, schizophrenia or bipolar disorder,” Discover USC (student: Reagan Farmer; mentor: MPKelly)
2019 University of South Carolina Graduate Student SPARC Research Award, “The role of PDE11A in social isolation” ($5000; P.I. Katy Pilarzyk; mentor: MPKelly).
2018 University of South Carolina Magellan Scholar Award, “The role of PDE2A in major depression, bipolar disorder and schizophrenia” ($2500; P.I. Reagan Farmer, mentor: MPKelly)
2018 University of South Carolina Magellan Mini-grant, “Identification of Age-related PDE11A increases in hippocampal subregions and subcellular domains” ($1000; P.I. David Smith, mentor: MPKelly)
2018 University of South Carolina Magellan Mini-grant, “The role of PDE2A in major depression, bipolar disorderand schizophrenia” ($750; P.I. Reagan Farmer, mentor: MPKelly)
2018 Winner Best Poster, “The role of PDE11A in isolation-induced neuroinflammation,” Discover USC (student: Katy Pilarzyk; mentor: MPKelly)
2018 University of South Carolina Science Undergraduate Research Fellowship, “Defining signals that control the subcellular compartmentalization and catalytic activity of the enzyme PDE11A4” ($3000; “Changes in Localization of PDE11A with an Inactivating Mutation”, P.I. Alvina Emran; mentor: MP Kelly)
2018 Abstract selected for Talk, “The role of PDE11A in isolation-induced neuroinflammation and social deficits,” Gordon Research Seminar on Cyclic Nucleotide Phosphodiesterases (student: Katy Pilarzyk; mentor: MP Kelly)
2018 Travel Awards from the USC and USCSoM Graduate Student Offices ($500 each; Katy Pilarzyk; mentor: MP Kelly)
2018 Honorable mention for Best Poster, “The role of PDE11A in isolation-induced neuroinflammation,” USC Neuroscience Retreat (student: Katy Pilarzyk; mentor: MP Kelly)
2018 NDSEG Fellowship Finalist (student: Katy Pilarzyk; mentor: MP Kelly)
2017 Honorable mention for Best Poster, “The role of PDE11A in isolation-induced neuroinflammation and social deficits,” USC Neuroscience Retreat (student: Katy Pilarzyk; mentor: MP Kelly)
2017 Dwight Camper Outstanding Undergraduate Research Award, South Carolina Academy of Science (student: Neema Patel; mentor: MPKelly)
2017 1st place Best Oral Presentation, “Identification of intramolecular signals controlling PDE11A4 subcellular compartmentalization,” Discover USC (student: William Capell; mentor: MP Kelly)
2017 1st Place Best Poster, “Identifying which cells and subcellular compartments in the brain express PDE9A and how that expression changes with age.” University of South Carolina Discovery Day (student: Neema Patel; mentor: MP Kelly)
2017-2018 University of South Carolina Science Undergraduate Research Fellowship, “Transient amnesia: The role of PDE11A4 in the systems consolidation of social memories” ($4500; P.I.: Jennifer Klett; mentor: MP Kelly)
2017 University of South Carolina Magellan Scholar Fellowship, “Transient amnesia: The role of PDE11A4 in the system consolidation of social memories” ($3000; P.I.: Jennifer Klett; mentor: MP Kelly)
2017 University of South Carolina Magellan Mini-grant, “Transient amnesia: The role of PDE11A4 in the system consolidation of social memories” ($750; P.I.: Jennifer Klett; mentor: MP Kelly)
2016 Abstract selected for talk, “Identification of intramolecular signals controlling PDE11A4 subcellular " Gordon Research Conference on Cyclic Nucleotide Phosphodiesterases (student: William Capell; mentor: MP Kelly)
2016 Abstract selected for talk, “Identifying which subcellular compartments in the brain express PDE9A and how that expression changes with age.” Gordon Research Conference on Cyclic Nucleotide Phosphodiesterases (student: Neema Patel; mentor: MP Kelly).
2016 Betty Fundenberg Biomedical Research Award for outstanding biomedical research, University of South Carolina (student: Neema Patel; mentor: MP Kelly)
2016-2017 University of South Carolina Science Undergraduate Research Fellowship, “Defining signals that control the subcellular compartmentalization and catalytic activity of the enzyme PDE11A4” ($4500; P.I. William Capell; mentor: MP Kelly)
2016 1st Place Poster, “Identifying which cells and subcellular compartments in the brain express PDE9A and how that expression changes with age.” University of South Carolina Discovery Day (student: Neema Patel; mentor: MP Kelly)
2016 ASPET Individual Summer Undergraduate Research Fellowship (P.I., William Capell; mentor: MP Kelly)
2016 Travel Award Grant, USC Honors College (Student: Will Capell; mentor: MP Kelly)
2016 Travel Award Grant, USC Honors College (Student: Neema Patel; mentor: MP Kelly)
2016 University of South Carolina Magellan Scholar Fellowship, “Identifying which cells and sub-cellular compartments in the brain express PDE9A and how that expression changes with age” ($3000; P.I. Neema Patel; mentor: MP Kelly)
2016 University of South Carolina Magellan Scholar Fellowship, “Defining signals that control the subcellular cellular compartmentalization and catalytic activity of the enzyme PDE11A4” ($1000; P.I. William Capell; mentor: MP Kelly)
2016 University of South Carolina Magellan Mini-grant, “Identifying which cells and subcellular compartments in the brain express PDE9A and how that expression changes with age” ($1000; P.I. Neema Patel; mentor: MP Kelly)
2016 University of South Carolina Magellan Mini-grant, “Defining signals that control the subcellular compartmentalization and catalytic activity of the enzyme PDE11A4” ($1000; P.I. William Capell; mentor: MP Kelly)
2015-2017 University of South Carolina Science Undergraduate Research Fellowship, “Characterizing PDE9A in the brain and analyzing its age-related effects” ($4,500; P.I. Neema Patel; mentor: MP Kelly)
2015 Travel Award Grant, ADD Program Symposium (Student: Will Capell; mentor: MP Kelly)
2015 Travel Award Grant, USC Honors College (Student: Will Capell; mentor: MP Kelly)
2014 Travel Award Grant, USC Honors College (Student: Geetanjali Pathak; mentor: MP Kelly)
2014 Best Student Poster Award, “Homodimerization and N-terminal phosphorylation control the subcellular trafficking of PDE11A4.” (Student: Geetanjali Pathak; mentor: MP Kelly)
2014 1st Place Poster, “Homodimerization and N-terminal phosphorylation control the subcellular trafficking of PDE11A4.” University of South Carolina Discovery Day. (Student: Geetanjali Pathak; mentor: MP Kelly)
2013 National Science Foundation Graduate Research Fellowship, “The effect of PDE11A signaling in social behaviors” ($32K stipend plus tuition for 3 years; P.I. Ivory Harding; mentor: MP Kelly)
2012-2014 University of South Carolina Science Undergraduate Research Fellowship, “PDE11A subcellular localization” ($4.500; P.I. Geetanjali Pathak; mentor: MP Kelly)