McMaster University

Medical Sciences
Graduate Program

Scope of Search

Margaret Fahnestock

Margaret Fahnestock

PhD
Professor

Research Interests

Neurotrophic factors are proteins essential for nervous system development and function. The biosynthesis and regulation of neurotrophins such as NGF and BDNF are disrupted in many neurodegenerative and psychiatric diseases. My laboratory studies neurotrophin gene expression, regulation, signaling and trafficking and their role in Alzheimer's disease, autism and peripheral nerve injury. By studying dysregulation of NGF and BDNF in these disorders, we have come to understand how the proper amount of neurotrophin reaches the proper cells at the right time, and the consequences if it doesn’t. We use human post mortem brain tissue, animal models and cell culture to study transcriptional, translational and post-translational regulation, signaling and transport of neurotrophins and their receptors in health and disease. Understanding how neurotrophins are dysregulated in Alzheimer’s disease and autism is crucial to identifying new therapeutic approaches and targets for these devastating disorders.


Current projects include:

  1. Molecular mechanisms of BDNF transcriptional down-regulation and proNGF protein dysfunction in Alzheimer’s disease
  2. BDNF post-translational modification and signaling pathway disruptions in autism
  3. Axonal transport of pro-neurotrophins
  4. Mechanisms of lifestyle influences on neurotrophin levels
  5. Regulation of muscle-derived neurotrophic factors following surgical and stimulation treatments for peripheral nerve injury

Molecular biology, biochemistry, cell culture, real-time qRT-PCR, Western blotting, ELISA, neurite outgrowth assays, animal models, behavioural assays.

Contact

McMaster University
Health Sciences Centre

telephone: (905) 525-9140 ext. 23344
email: fahnest@mcmaster.ca

Program Area

Physiology & Pharmacology

Research Areas

Molecular Neurobiology

Selected Publications

  • Increased proNGF and decreased BDNF in non-Alzheimer's disease tauopathies. Belrose JC, Masoudi R, Michalski B, Fahnestock M. Neurobiol. Aging 2014; 35:926-933

  • Sensory nerve cross-anastomosis and electrical muscle stimulation synergistically enhance functional recovery of chronically denervated muscle.Willand MP, Holmes M, Bain JR, de Bruin H, Fahnestock M. Plast Reconstr Surg. 2014 Nov;134(5):736e-45e.
  • Altered balance of proteolytic forms of pro-brain-derived neurotrophic factor in autism. Garcia KLP, Yu G, Nicolini C, Michalski B, Garzon D, Chiu VS, Tongiorgi E, Szatmari P, Fahnestock M. J. Neuropathol. Exp. Neurol. 2012; 71(4):289-297.