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James P. Fawcett, PhD Professor Departments of Pharmacology and Surgery, Dalhousie University Website | This e-mail address is being protected from spambots. You need JavaScript enabled to view it | Publications Tel: (902) 494-3659

Research

Formation of neurons, synapses and spinal cord circuits

Developmental neurobiologist Dr. Jim Fawcett is exploring fundamental processes that underlie the formation of individual neurons and synapses, and of the complex spinal circuits that control walking. His findings will shed light on potential therapies for treating neurodegenerative diseases and repairing damaged spinal cords.

Dr. Fawcett holds more than $1.3 million from the Canadian Institutes of Health Research, NSERC and the EJLB Foundation to investigate:

• the protein signaling events behind neuronal polarity, the process by which a developing neuron differentiates its parts so that one of many frond-like processes becomes the axon (while the others become dendrites)
• how a neuron establishes connections with other neurons
• how certain neuron populations in the spinal cord establish linkages with one another to control the rhythmic pattern of walking.

Functional Restoration

Dr. Fawcett is one of six Dalhousie investigators involved in the $14 million Functional Restoration Project, which received nearly $6 million from the Canada Foundation for Innovation (CFI). Another $8 million for new equipment will further aid the researchers as they explore strategies for restoring function in people with injuries and diseases affecting mobility.

Among many collaborative projects, Dr. Fawcett is working with Dr. Vic Rafuse to explore the use of Induced Pluripotent Stem Cells (iPS cells) as a source of adult human stem cells for engineering into neuro-regenerative therapies.

Dr. Fawcett works extensively with Drs. Vic Rafuse, Angelo Iulianella, Ying Zhang and Turgay Akay. These researchers form the laboratory-based nucleus of the Mobility Project.

Academic background

After earning a B.Sc. in biology from McMaster University in Hamilton, Ontario, Jim Fawcett went on to complete an M.Sc. in biomedical sciences, with a focus on nervous system research. He then turned his attention to global health issues, obtaining an MSc(T) in education through McMaster’s Faculty of Health Sciences. From there, he went to McGill University to pursue a PhD in neurology and neurosurgery, which he achieved with distinction. Funding from the Canadian Institutes of Health Research launched Dr. Fawcett’s postdoctoral studies at the University of Toronto’s Samuel Lunenfeld Research Institute. In 2006, he was awarded a Tier II Canada Research Chair in the Molecular Neurobiology of Brain Repair and made the move to Halifax to join the departments of Pharmacology and Surgery in Dalhousie University’s Faculty of Medicine.

 Selected Publications

Cohen A*., Ross N.W., Smith P.M., and Fawcett J.P.(2017).  Method development and analysis of 17β-esterdiol, estriol and estrone in Anguilla rostrata tissue samples using liquid chromatography coupledelectrospray-differential ion mobility tandem mass spectrometry (2016b).  Rapid Communications in MassSpectrometry (RCM-16-0302) (*denotes my trainees).

Quinn D., Kolar A., Wigerius M.*, Gomm-Kolisko R., Atwi H., Fawcett J.P. and Kruger, R. S.(2017). Panneurexin perturbation results in compromised synapse stability and a reduction in readily releasable synaptic vesicle pool size.  Scientific Reports. 7(42920): 1-13.

Wigerius, M.*, Diab, A.*, Quinn, D.*, Clattenburg, L.*, Qi, J.*, Lane, C.*, Kolar, A., Krueger, S., and Fawcett J.P.(2017).  The polarity protein Angiomotin controls dendritic spine development.  Neuron.

Alzahrani F.*, Clattenburg L.*, Muruganandan S., Bullock M.S., MacIsaac K.*, Wigerus M.*, Williams B.A, Graham E.R., Rigby M.H., Trites J.R.B., Taylor S.M., Sinal C.J., Fawcett J.P.^, and Hart R.D.^ (^Cocorresponding author). (2017).  The Hippo component YAP localizes in the nucleus of human papilloma virus positive oropharyngeal squamous cell carcinoma.  J. Otolaryngol Head Neck Surg.46(15): 1-7.

Cohen A.*, Soto A., and Fawcett J.P.(2016). Determination of Flow Rates in Capillary Liquid Chromatography Coupled to a Nano Electrospray Source using Droplet Image Analysis Software (2016a). Analytical Chemistry. 88: 7476-7480.

Drange H., Muruganandan, S., Fawcett J.P., and Sinal C.J.(2016).  Adipocyte-secreted chemerin is processed to a variety of isoforms and influences MMP3 and chemokine secretion through an NFkBdependent mechanism.  Mol Cell Endrocrinol.436: 114-129.

Toma J.S., Shettar B.C., Chipman P.H., Pinto D.M., Borowska J.P., Ichida J.K., Fawcett J.P., Zhang Y., Eggan K., and Rafuse V.F.(2015).  Motoneurons Derived from Induced Pluripotent Stem Cells Develop Mature Phenotypes Typical of Endogenous Spinal Motoneurons.  Journal of Neuroscience. 35(3): 1291-1306.

Blacklaws J., Deska-Gauthier D., Jones C.T., Petracca Y.L., Fawcett J.P., Glover J., Lanuza G.M., and Zhang Y. (2015).  Sim1 is required for the migration and axonal projections of V3 interneurons in the developing mouse spinal cord.  Developmental Neurobiology. 75: 1003-1017.

Lane* C., Qi J., and Fawcett J.P.(2015).  NCK is critical for the development of deleted in colorectal cancer (DCC) sensitive spinal circuits. Journal of Neurochemistry. 134: 1008-1014.

Clattenburg* L., Wigerius* M., Qi J., Rainey J.K., Rourke J.L., Muruganandan S., Sinal C.J., Fawcett J.P. (2015).  NOS1AP functionally associates with YAP to regulate Hippo signaling. Molecular and Cellular Biology. 35(13): 2265-77.

Kai F., Fawcett J.P., Duncan R.(2015).  Synaptopodin-2 Induction of Non-Directional Lamellipodia Formation and Focal Adhesion Assembly Correlates with Enhanced Prostate Cancer Cell Migration. Oncotarget. 10(6): 11162-11174.

Wallingford J.K., Deurveilher S., Currie R.W., Fawcett J.P., and Semba K.(2014).  Increases in mature brain-derived neurotrophic factor protein in the frontal cortex and basal forebrain during chronic sleep restriction in rats: Possible role in initiating allostatic adaptation. Neuroscience. 277: 174-183.

Soundararajan P.*, Fawcett J.P.^, and Rafuse V.F.^ (^Co-corresponding). (2010).  Guidance of postural motoneurons requires MAPK/ERK signaling downstream of fibroblast growth factor receptor 1. The Journal of Neuroscience. 30(19): 6595-6606.

Richier L*., Williton K., Clattenburg L*., Colwill K., O'Brien M*., Tsang C., Kolar A., Zinck N*., Metalnikov P., Trimble W.S., Krueger S.R., Pawson T., and Fawcett J.P.(2010).  NOS1AP associates with Scribble and regulates dendritic spine development. The Journal of neuroscience. 30(13): 4796-4805.

Schmoranzer J , Fawcett JP , Segura M , Tan S , Vallee RB , Pawson T , Gundersen GG. (2009). Par3 and dynein associate to regulate local microtubule dynamics and centrosome orientation during migration. Current Biology. 19(13): 1065-1075.

Moser SL , Harron SA , Crack J , Fawcett JP , Cowley EA. (2008).  Multiple KCNQ potassium channel subtypes mediate basal anion secretion from the human airway epithelial cell line Calu-3. The Journal of membrane biology. 221(3)

Fawcett JP , Georgiou J , Ruston J , Bladt F , Sherman A , Warner N , Saab BJ , Scott R , Roder JC , Pawson T. (2007).  Nck adaptor proteins control the organization of neuronal circuits important for walking. Proceedings of the National Academy of Sciences of the United States of America. 104(52):20973-20978

Soundararajan, P., Fawcett, J.P.*, Rafuse, V.*, (2010) Directed growth of postural motor axons requires activation of the MAPK/ERK signaling pathway. 30:6595-6606

Richier, L., Williton, K., Clattenburg, L., Colwill, K., O’Brien, M., Tsang, C., Kolar, A., Zinck, N., Metalnikov, P., Trimble, W.S., Krueger, S., Pawson, T.*, Fawcett, J.P.* (2010) NOS1AP associates with Scribble and regulates dendritic spine development. J. Neurosci. 30:4796-4805.

Schmoranzer, J., Fawcett J.P., Segura, M., Tan,S., Vallee, R.B., Pawson, T., and Gundersen, G.G (2009) Par3 associates with dynein light intermediate chain 2 to locally regulate microtubule dynamics and polarize the centrosome in migrating cells. Current Biology 19:1065-1075.

Moser, S.L., Harron, S.A., Crack, J., Fawcett, J.P., Cowley, E.A. (2008) Multiple KCNQ Potassium Channel Subtypes Mediate Anion Secretion from the Human Airway Epithelial Cell Line Calu-3. J Membr Biol 221:153-163.

Fawcett, J.P., Georgiou, J., Ruston, J., Bladt, F., Sherman, N., Warner, N., Saab, B.J., Scott, R., Roder J., Pawson, T. (2007) Nck adaptor proteins control the organization of neuronal circuits important for walking. PNAS 104:20973-20978.

Hardy, W.R., Li, L., Wang, Z., Sedy, J., Fawcett, J.P., Frank, E., Kucera, J., Pawson, T. (2007) Combinatorial SchA docking interactions support diversity in tissue morphogenesis. Science 317:251-256.

Chan, J.R., Jolicoeur, C., Yamauchi, J., Elliot, J., Fawcett, J.P., Ng, B.K., Cayouette, M. (2006) The polarity protein Par-3 directly interacts with p75NTR to regulate myelination. Science 314:832-836.

Aranda, V., Haire, T., Nolan, M.E., Calarco, J.P., Rosenberg, A.Z., Fawcett, J.P., Pawson, T., Muthuswamy, S.K. (2006) Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control. Nat. Cell Biol. 8:1235-1245.

Wells C*, Fawcett, J.P.*, Traweger A., Yamanaka, Y., Goudreault, M., Elder, K., Kulkarni, S., Gish, G., Virag, C., Lim C., Colwill C., Starostine, A., Metalnikov, P., Pawson, T. (2006) A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells.Cell125, 535-548.

Jin, J., Smith, F.D., Stark, C., Wells, C.D., Fawcett, J.P., Kulkarni, S., Metalnikov, P., O’Donnell, P., Taylor, P., Taylor, L., Zougman, A., Woodgett, J.R., Langeberg, L.K., Scott, J.D., and Pawson T (2004) Protemomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. Curr. Biol. 14:1436-50.

Plant P.J. *, Fawcett J.P. *, Lin D.C., Holdorf A.D., Binns K., Kulkarni S., Pawson T. (2003) A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl. Nature Cell Biol. 5:301-8

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