Patricia Maness

Keywords: cell adhesion molecules, neurodevelopment,neural connectivity, signal transduction

Patricia Maness

Professor of Biochemistry and Biophysics
(PhD - University of Texas)

ACCEPTING STUDENTS

120 Mason Farm Road, CB# 7260
3020 Genetic Medicine
Chapel Hill, NC 27599-7260
919-966-5702

Maness Lab Website

HONORS & AWARDS

  • Pogue Fellowship for Scholarly Research: 2012
  • Member NIH Neurodifferentiation, Plasticity, and Regeneration (NDPR) Study Section: 2013 - current
  • Distinguished Investigator Award, National Alliance for Research on Schizophrenia and Depression (NARSAD): 1999-2002
  • NIH Research Career Development Award: 1988-1992
  • Jefferson-Pilot Award in Academic Research: 1984

 RESEARCH SUMMARY

How neuronal circuitry in the brain is established during development and refined in the adult is a central unanswered question in neuroscience. Neural recognition molecules expressed on the neuronal surface are pivotal players in developing cortical circuits. Among the most relevant of these molecules to human disease are members of the NCAM and L1 family (L1, CHL1, NrCAM, Neurofascin). Each of these cell recognition molecules has established functions in axon guidance that mediate correct topographic synaptic targeting of axons, while exciting new findings reveal that they also have vital functions in regulating synaptogenesis and plasticity of cortical networks. Importantly, mutations in neural adhesion molecule genes may contribute to susceptibility to human neuropsychiatric diseases such as schizophrenia, autism spectrum disorders, and intellectual disability. To study the normal and abnormal function of neural cell adhesion molecules in brain development and function, our laboratory uses a multidisciplinary approach to generate and analyze novel mouse genetic models of neurodevelopmental disorders. Neural adhesion molecules of the immunoglobulin superfamily (Ig-CAMs) are risk factors for neurodevelopmental disorders such as autism, schizophrenia, and intellectual disability. Maness transformed our understanding of how IgCAMs function by discovering that they are not molecular “glue” but are signaling receptors that establish and refine neuronal connectivity in the mammalian brain. Using novel mouse models she demonstrated that IgCAMs mediate topographic axon targeting and synaptogenesis, and identified their signaling pathways through Src, RhoA and MAP kinases. She was first to determine that a normal proto-oncogene product, c-Src, functions to regulate neuronal axon guidance, rather than proliferation, distinguishing it from its oncogenic counterpart. This finding had widespread implications for our understanding that proto-oncogenes play normal roles in cell differentiation.

SELECTED PUBLICATIONS

  • Sullivan CS, Gotthard I, Wyatt EV, Bongu S, Mohan V, Weinberg, R, and Maness PF. Perineuronal Net Protein Neurocan Inhibits NCAM/EphA3 Repellent Signaling in GABAergic Interneurons Scientific Reports. 8:6143, 2018. PMID: 29670169.
  • Neuronal Cell Adhesion Molecule 1 (NrCAM) is expressed by sensory cells in the cochlea and is necessary for proper cochlear innervation and sensory domain patterning during development. Harley         RJ, Murdy JP, Wang, Z, Ropp RF, Park SH, Maness PF, Manis PB, and Coate TM. Developmental Dynamics, in press 2018.   PMID:29536590.
  • Temporal Regulation of Dendritic Spines through NrCAM-Semaphorin3F Receptor Signaling in Developing Cortical Pyramidal Neurons. Mohan, V, Sullivan CS, Guo J, Wade SD, Majumder S, Agarwal A, Anton ES, Temple BS, and Maness PF.  Cerebral Cortex, 1-15, 2018. PMID: 29415226.
  • Zhang X, Kratz MB, Sullivan CS, Maness PF*, Manis PB*. NCAM regulates the spatial organization of inhibitory interneuron synapses onto layer 2/3 pyramidal cells of anterior cingulate cortex. Frontiers in Neural Circuits. 11 (2017) 1-18. *equal contributors
  • Sullivan CS, Kümper M, Temple BS, Maness PF. The Neural Cell Adhesion Molecule (NCAM) Promotes Clustering and Activation of EphA3 Receptors in GABAergic Interneurons to Induce Ras Homolog Gene Family Member Rho (RhoA)/Rho-associated protein kinase (ROCK)-mediated Growth Cone Collapse. Journal of Biological Chemistry. (2016) 291: 26262-26272. PMID: 27803162.
  • Mohan,V, Demyanenko, GP, Zhang, X, Brennaman, LH, Dharbal KES, Tran TS, Manis PB, and Maness, PF. Neural cell adhesion molecule NrCAM regulates Semaphorin 3F-induced dendritic spine remodeling. Journal of Neuroscience.  34 (2014) 11274-87. PMCID: PMC4138338

Link to all pubs

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