Dusica Maysinger was trained at the University of Southern California, USA, where she obtained her MSc in 1973 and PhD in 1976. Her PhD thesis dealt with the development of radiolabeled steroids and structural analogs for diagnostic purposes and drug design, based on structure-function relationships. These studies steered her towards the exciting field of degenerative changes in the nervous system, which was the focus of her study as an Alexander von Humoldt fellow at the Max Planck Institute in Munchen and at the University of Heidelberg, Germany. Subsequently, as a member of Dr Claudio Cuello’s team at Oxford University in the UK, she came to McGill University as a postdoctoral fellow where she continued to research molecular mechanisms underlying degenerative changes in the nervous system. One aspect of this work included diabetes-induced neurodegenerative changes in the peripheral nervous system, and the development of nanoparticles for cellular imaging and therapeutic interventions. Dr Maysinger was appointed assistant professor at McGill University in 1987, and is presently a full professor in the Department of Pharmacology and Therapeutics at McGill. Today her research team includes numerous scientific collaborators. Currently, her lab is focused on investigating the mechanisms underlying cell death, neurodegeneration, and regenerative growth of the central and peripheral nervous system. The use of nanoparticles as biosensors and for therapeutic purposes continues to be an integral aspect of her research.

Dr Maysinger showed that a balance between signal intensity duration and location between JNK, p38 and Akt plays a role in beta cell viability in human islets. Her group also showed that INGAP peptide (and protein) can enhance mitochondrial metabolic activity in human islets and in primary dorsal root ganglia dispersed or explanted cultures. Moreover, the peptide, in combination with trophic factors, can promote neurite outgrowth of compromised peripheral nerves in vivo. With respect to nanomedicine, Maysinger’s group demonstrated how some of the fluorescent nanoparticles can be used to determine their fate in living cells, and to image whole organisms in real time. Maysinger et al. (Nano Lett 2007) showed for the first time, how glial cells respond, in a dynamic manner, to different classes of nanoparticles in transgenic animals. Similar in vivo imaging studies, together with concurrent mechanistic investigations, are ongoing to assess the effectiveness of therapeutic interventions in stimulating regenerative growth of the compromised peripheral nervous system in diabetes.

Current projects in the laboratory can be divided into three areas:

Development and assessment of nanoparticles for drug delivery. The objective of these studies is to identify and select the type of nanoparticles, composed of biocompatible polymers, that is best suited for the construction of a drug-delivery nanosystem. This nanosystem not only allows for targeted delivery, but also reduces side effects of therapeutics, including inhibitors of kinases, anti-inflammatory agents and antioxidants.

Imaging of nanoparticles and their cellular-interactions in real time. We use quantum dots and other fluorescent nanoparticles to examine their effects on different types of cells relevant for regeneration and cell/tissue repair. Our focus is on glial cells, which can either facilitate or impair the regeneration process depending on their degree of activation, the secretion of trophic factors, and the release of cytotoxic agents. We explore the morphological and biochemical changes of organelles affected by nanoparticles. We use multiphoton imaging of living cells to reveal the status of mitochondria, lysosomes and lipid droplets. Functional and morphological properties of these organelles are changed in nervous systems affected by diabetes and other neurodegenerative disorders. Our investigations suggest that addition of nanoparticles to the impaired nervous system can affect the organelles of nearby glial cells, and in turn, alter the functions of these glial cells.

Neuro-Lipidomics. This is a new direction we have recently begun in collaboration with a neurolipidomic group at Washington University. We seek to define how lipids in the nervous system contribute to the regenerative growth (stimulated by therapeutics) in the compromised nervous system (i. e. diabetic neuropathy). We are currently testing the hypothesis that the balance between fatty acids and different ceramide species are critically involved in regeneration and repair of the nervous system.

Our laboratory addresses these questions using a broad panoply of techniques including the use of rodent knockout models, RNA silencing, lipidomics, in vivo functional assays, biochemical assays and confocal microscopy.