Dusica Maysinger, PhD
Professor of Pharmacology and Therapeutics
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.
Selected Scientific Contributions
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.
Click here for PubMed listing
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.