David C. Martinelli, PhDAssistant Professor of Neuroscience
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Degree | Institution | Major |
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BS | University of Rochester | Molecular Genetics |
PhD | Johns Hopkins University and Carnegie Institution for Science | Developmental Biology; Thesis Advisor: Dr. Chen-Ming Fan |
Post-Graduate Training
Training | Institution | Specialty |
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Postdoctoral | Stanford University | Advisor: Dr. Thomas Südhof, 2013 Nobel laureate. Research Focuses: Neuroscience, Mouse Behavior, Virus Vectors, Genetics, Cellular Biology and Biochemistry |
Name & Description | Category | Role | Type | Scope | Start Year | End Year |
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Admissions Committee for Ph.D. graduate program in Biomedical Science at UConn Health | Advisory Committee | member | UConn Health | University | 2016 | 2021 |
A synapse is the fundamental structural unit by which neurons communicate. The importance of synapses cannot be overstated as their collective activities impact every moment of our subconscious and conscious mind. Furthermore, synapses are formed and continuously restructured throughout life based on different experiences, which ultimately shapes us as individuals with unique memories, thoughts, skills, and personalities. How the trillions of synapses in a brain are wired into functional neural networks and the mechanisms of experience-dependent synaptic plasticity are important outstanding questions.
I am particularly fascinated by synaptic adhesion proteins, which bind across the synaptic cleft to form a molecular interface between pre- and post-synaptic membranes and also initiate intercellular trans-synaptic signaling. These proteins are at the junction of our genes and experiences and are critical for initiating and stabilizing synaptic changes in a multitude of ways. My research goal is to understand the molecular logic of how synaptic adhesion proteins, in a defined brain circuit, orchestrate synaptic formation, modification, and function, and to ultimately provide an explanation for how these events influence behaviors, in particular the aberrant behaviors associated with neuropsychiatric diseases.
The immediate focus of my research is on the neuronally secreted C1q-like family of proteins. The lab will study the biochemical interactions with their pre- and post-synaptic protein binding partners, their synaptic signaling activities, and their eventual behavioral consequences. A priori, their localization in the synaptic cleft almost predestines them to have neuropsychiatric disease relevance. Genetic analyses of C1q-like mutant mice revealed behavioral abnormalities potentially resembling several neuropsychiatric diseases, including ADHD, schizophrenia, and addiction predisposition. How C1q-like proteins and their binding partners influence synapses and ultimately behaviors is unknown. The techniques used in the lab to answer these questions encompass biochemistry, genetics, cell biology, circuit analysis using viral vectors, and mouse behavioral assays.
Accepting Lab Rotation Students: Spring 1 and 2 Block 2025
Journal Articles
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Stepwise molecular specification of excitatory synapse diversity onto cerebellar Purkinje cells.
Nature neuroscience 2024 Dec;
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C1ql1 expression in oligodendrocyte progenitor cells promotes oligodendrocyte differentiation.
The FEBS journal 2024 Sep;
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Creation of a novel CRISPR-generated allele to express HA epitope-tagged C1QL1 and improved methods for its detection at synapses.
FEBS letters 2024 Jun;
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C1ql1 is expressed in adult outer hair cells of the cochlea in a tonotopic gradient.
PloS one 2021 May;16(5):e0251412
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C1QL3 promotes cell-cell adhesion by mediating complex formation between ADGRB3/BAI3 and neuronal pentraxins.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2020 Dec;35(1):e21194
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Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of Adult Neurogenesis.
Cell stem cell 2020 Feb;26(2):277-293.e8
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FAM19A1, a brain-enriched and metabolically responsive neurokine, regulates food intake patterns and mouse behaviors.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2019 Nov;fj201901232RR
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Anatomical and Behavioral Investigation of C1ql3 in the Mouse Suprachiasmatic Nucleus.
Journal of biological rhythms 2017 May;32222-236
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Expression of C1ql3 in Discrete Neuronal Populations Controls Efferent Synapse Numbers and Diverse Behaviors.
Neuron. 2016 Sep;91(5):1034-51
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Structures of C1q-like proteins reveal unique features among the C1q/TNF superfamily.
Structure. 2015 Apr;23(4):688-99
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Gas1 is a receptor for sonic hedgehog to repel enteric axons.
P.N.A.S. 2015 Jan;112(1):E73-80
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Presynaptic neurexin-3 alternative splicing trans-synaptically controls postsynaptic AMPA receptor trafficking.
Cell. 2013 Jul;154(1):75-88
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The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins.
P.N.A.S. 2011 Feb;108(6):2534-9
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A sonic hedgehog missense mutation associated with holoprosencephaly causes defective binding to GAS1.
The Journal of Biological Chemistry. 2009 Jul;284(29):19169-72
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Primary cilia regulate Shh activity in the control of molar tooth number.
Development. 2009 Mar;136(6):897-903
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Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog.
The Journal of Clinical Investigation. 2007 Jun;117(6):1575-84
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Gas1 extends the range of Hedgehog action by facilitating its signaling.
Genes & Development. 2007 May;21(10):1231-43
Letters
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Cerebellins meet neurexins (Commentary on Matsuda & Yuzaki).
The European Journal of Neuroscience. 2011 Apr;33(8):1445-6
Reviews
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International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.
Pharmacological Reviews. 2015 Jan;67(2):338-67
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The role of Gas1 in embryonic development and its implications for human disease.
Cell Cycle. 2007 Nov;6(21):2650-5