St. Boniface Hospital Research

Dr. Freda Miller is a cell and molecular neurobiologist at The Hospital for Sick Children Research Institute, a professor at the University of Toronto, and holds the Canada Research Chair in Developmental Neurobiology. Dr. Miller has authored more than 100 scientific papers, reviews and book chapters and has 13 patents (issued and pending).

Dr. Miller is best known for her studies of neuronal stem cells and of neuronal growth, survival and apoptosis. Major findings from her lab have provided evidence that mammalian dermis contains a multipotent stem cell that can be isolated and purified, that the p75 neurotrophin receptor is apoptotic in neurons, and that a p53 family member, truncated p73, plays an essential anti-apoptotic role in the nervous system.

Dr. Miller is a fellow of the Royal Society of Canada, a councillor of the American Society for Neurosciences, and an HHMI International Research Scholar. She obtained her PhD in Molecular Biology from the University of Calgary in 1984 and completed her post-doctoral research at the Scripps Research Foundation with Dr. F.E. Bloom. She accepted her first faculty position as an Alberta Heritage Foundation Scholar at the University of Alberta. Five years later she moved to the Montreal Neurological Institute and McGill University as the Coordinator for the Centre for Neuronal Survival. She has held her current position in Toronto for the last five years. Dr. Miller is also a founder of Aegera Therapeutics Inc., a biotechnology company based in Montreal and Ottawa.

Fellow, Royal Society of Canada
Councillor, American Society for Neurosciences

• Neural stem cells
• Neurotrophin regulation of neuronal survival, growth and connectivity
• Role of p53 family in the nervous system
• Molecular regulation of neurogenesis

During embryonic development the nervous system is confronted with a problem of enormous complexity; to progress from a thin sheet of neuroepithelial cells to a network of neuronal circuitry that is able to process sensory information and generate an appropriate motor output. One of the ways that the mammalian nervous system achieves this end point is by overproducing both neurons and neuronal connections, and then eliminating those cells and/or connections that are not appropriate. However, this is not something that is limited to the developing nervous system. Many of the same cellular mechanisms remain "in place" in adult animals, thereby allowing structural and/or functional remodeling in response to physiological stimuli, and providing repair mechanisms for the injured and traumatized mature nervous system.

These complex developmental processes are determined by an intimate interplay between intrinsic cellular programs and environmental cues. Within this broad context, my laboratory is interested in understanding how growth factors and neural activity regulate the genesis, survival and growth of developing neurons and regulate the establishment of appropriate neuronal connectivity

1. CIHR Operating Grant, "The p53 family and Neuronal Apoptosis", 2005-2010. F.D. Miller, principal investigator, D.R. Kaplan, coinvestigator.
   
2. CIHR Operating Grant, "Molecular Control of Cortical Neurogenesis", 2002-2007. F.D. Miller, principal investigator, D.R. Kaplan, coinvestigator.
   
3. CIHR Operating Grant, "Characterization of SKPs, Multipotent Adult Stem Cells from Mammalian Dermis", 2006-2011. F.D. Miller, principal investigator.
   
4. CIHR Operating Grant, "Trk Tyrosine Kinase Signal Transduction Pathways in Primary Neurons", 2002-2007. D.R. Kaplan, principal investigator, F.D. Miller, coinvestigator.
   
5. HHMI International Research Scholar operating grant, "SKPs: From basic biology to therapeutic utility", 2006-2011. F.D. Miller, principal investigator.
   
6. Neurosciences Canada Group Grant, "Novel Approaches to White Matter Repair", 2004-2006. F.D. Miller, principal investigator. Coinvestigators, D. Kaplan, S. Weiss, W. Tetzlaff.
   
7. Canadian Stroke Network and Canadian Stem Cell Network, "Adult Stem Cells to Treat Stroke", 2003-2007. C. Morshead and S. Weiss, principal investigators, F.D. Miller, coinvestigator.
   

Gauthier AS, Furstoss O, Araki T, Chan R, Neel BG, Kaplan DR, Miller FD. (2007) Control of CNS cell-fate decisions by SHP-2 and its dysregulation in Noonan syndrome. Neuron 54, 245-262.

Miller FD, Gauthier AS. (2007) Timing is everything: making neurons versus glia in the developing cortex. Neuron 54, 357-369.

McKenzie IA, Biernaskie J, Toma JG, Midha R, Miller FD. (2006) SKPs generate myelinating Schwann cells for the injured and dysmyelinated nervous system. J. Neurosci. 26, 6651-6660.

Jacobs WB, Govoni G, Ho D, Atwal JK, Barnabé-Heider F, Keyes WM, Mills AA, Miller FD, Kaplan DR. (2005) p63 is an essential proapoptotic protein during neural development. Neuron 48, 743-756.

Barnabé-Heider F, Wasylnka JA, Fernandes KJL, Porsche C, Sendtner M, Kaplan DR, Miller FD. (2005) Evidence that embryonic neurons regulate the onset of cortical gliogenesis via cardiotrophin-1. Neuron 48, 253-265.

Singh KK, Miller FD. (2005) Activity regulates positive and negative neurotrophin-derived signals to determine axon selection. Neuron 45, 837-845.

Fernandes KJL, McKenzie I, Mill P, Akhavan M, Smith K, Barnabé-Heider F, Kobayashi NR, Toma JG, Labosky PA, Kaplan DR, Hui C-C, Miller FD. (2004) An endogenous dermal niche for multipotent adult skin-derived precursor cells. Nat. Cell Biol. 6, 1082-1093.

Ménard C, Hein P, Savelson A, Yang X, Lederfein D, Barnabé-Heider F, Sterneck E, Peterson A, Johnson P, Vinson C, Miller FD. (2002) An essential role for a MEK-C/EBP pathway during growth factor-mediated cortical neurogenesis. Neuron 36, 597-610.

Toma JG, Akhavan M, Fernandes KJL, Fortier MP, BarnabéHeider F, Sadikot A, Kaplan DR, Miller FD. (2001) Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nature Cell Biol. 3, 778-784.

Pozniak C, Radinovic S, Yang A, McKeon F, Kaplan DR, Miller FD. (2000) An anti-apoptotic role for the p53 family member, p73, during developmental neuron death. Science 289, 304-306.

Patents

F.D. Miller, A. Gloster, J.G. Toma "Multipotent neural stem cells from peripheral tissues and uses thereof." U.S. Patent No. 6,787,355 B1, issued in 2004.

F.D. Miller, R. Slack. "Post-mitotic neurons containing adenovirus vectors that modulate apoptosis and growth." U.S. Patent No. 6,060,247, issued in 2000.

F.D. Miller, A. Gloster, CG. Causing, J.G. Toma. "Tubulin promoter regulates gene expression in neurons. " U.S. Patent No. 6,000,772, issued in 1999.

F.D. Miller, J.G. Toma, A. Gloster, C. Causing. "T.alpha.1 .alpha.-tubulin promoter and expression vectors ." U.S. Patent No. 5,661,032, issued in 1998.