About Maness

Dr. Patricia F. Maness is Professor of Biochemistry at the University of North Carolina School of Medicine. Over her distinguished career Dr. Maness has identified novel molecular signaling mechanisms that govern axon guidance and synaptogenesis in the developing mammalian brain through an innovative combination of mouse genetics, biochemistry, and molecular/cellular biology. She has trained 20 postdoctoral and 14 graduate fellows, and teaches neuroscience and biochemistry to medical and graduate students in the UNC School of Medicine.

Dr. Maness has received numerous awards including a Hilton Distinguished Investigatorship from the National Alliance for Research in Schizophrenia and Depression, Jefferson-Pilot Award, NIH Career Development Award, and Pogue Fellowship for Scholarly Research. She has been a full-term member of two NIH Study Sections: Neurodifferentiation, Plasticity, and Regeneration (NDPR; 2013-2017) and Neurology C (1988-1992). She has served on the Editorial Boards of Journal of Biological Chemistry and Frontiers in Neuroanatomy, and is currently Associate Editor of Frontiers in Neuroanatomy.

Dr. Patricia Maness received a B.A. in Microbiology from the University of Texas in 1970. She obtained her Ph.D. in Biochemistry from the University of Texas in 1975. Her thesis research was notable in identifying a key metabolic enzyme of mammalian nucleotide metabolism, Pyrimidine Nucleoside Monophosphate Kinase. This multi-substrate enzyme is essential for both DNA and RNA de novo synthesis, and displays an unusual mechanism for differential phosphorylation of CMP, dCMP, and UMP.  For this research she received the Sigma Xi Award for outstanding thesis. Dr. Maness then carried out postdoctoral training at Rockefeller University with Nobel laureate Dr. Gerald M. Edelman, where she was an Anna Fuller Fund Fellow and was later appointed Assistant Professor. There Dr. Maness made important contributions to understanding oncogenic growth regulation. She developed the first assay for the Src onco-protein, and demonstrated that this tyrosine kinase circumvents contact-dependent cell growth by disrupting actin cytoarchitecture.

Dr. Maness assumed a faculty position in the UNC Department of Biochemistry in 1980. There she turned to the role of proto-oncogenes in normal cell differentiation. She succeeded in developing an antibody to the cellular Src kinase, which enabled her to make a ground-breaking discovery that c-Src functions in the developing nervous system to promote axon growth rather than proliferation, thus distinguishing it from oncogenic Src. This finding had widespread implications for our general understanding of the roles of proto-oncogenes in cell differentiation. She went on to reveal that Src family kinases (Src, Fyn, Yes) promote axon growth as downstream signaling effectors of neural cell adhesion molecules. These studies transformed our understanding of cell adhesion molecules of the immunoglobulin superfamily (Ig-CAMs), establishing that they are signaling receptors and not simply molecular “glue.” Her laboratory systematically deciphered the signaling pathways leading from Ig-CAMs (L1, Close Homolog of L1, NrCAM, NCAM) through Src kinases, small GTPases and MAP kinases to control axon guidance within the motile nerve growth cone at the axonal tip.

Genetic alterations in Ig-CAMs are associated with human neuropsychiatric diseases, including autism (NrCAM), intellectual disability (L1, CHL1), and schizophrenia (NCAM). Maness’s laboratory generated novel Ig-CAM genetic models in mice that have illuminated the neural circuits controlled by these molecules and the biological consequences of Ig-CAM disease mutations. Her approach has identified mechanisms of topographic axon guidance resulting from Ig-CAM interaction with repellent guidance cues (Semaphorins and Ephrins) and cytoskeletal adaptors (Ankyrins), as well as pathological errors that disrupt connectivity in thalamo-cortical and retino-collicular circuits.

Maness has continued to make innovative discoveries in neurodevelopment. Recently she uncovered a novel mechanism of selective spine pruning, which eliminates overproduced dendritic spines and nascent synapses that arise during adolescence, thus shedding light on neurodevelopmental disorders with aberrant spine density and altered excitatory-inhibitory balance in cortical networks controlling social and cognitive behavior. She demonstrated that Ig-CAMs prune distinct populations of dendritic spines and excitatory synapses through their association with diverse  Semaphorin receptor complexes. She also discovered a related mechanism in which the adhesion molecule NCAM regulates the activity of ephrin receptor EphA3 to prune excess perisomatic contacts made by inhibitory basket interneurons in the developing prefrontal cortex, critical for working memory.