Research laboratories: Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University, 3655 Promenade Sir William Osler, Montreal, Canada H3G 1Y6.
Dr. Maysinger's areas of expertise include the mechanisms of drug actions, and signaling mechanisms in cell survival and differentiation. Her ongoing studies address a number of essential questions relevant to cell survival and processes leading to cell death, differentiation or survival. Dissection of signal transduction pathways involved in these processes in islet cells has been a focus of a long-term collaboration with Dr. Rosenberg. Special value of this multidisciplinary collaboration is in conducting the molecular biological studies in human islets and applying them in clinical setting. The key findings from our research are: (1) Islets are dying in a post isolation period by apoptosis and delayed necrosis, (2) An early pharmacological intervention during the isolation can enhance the islet survival, (3) Combined therapeutic intervention during and after the isolation as well as during the post-transplantation period is beneficial, and (4) Induction of islet neogenesis is a promising new direction to medical intervention in diabetes.
Complementary to these molecular biological and mechanistic
studies are investigations of the nano-delivery systems and other drug and
cell-delivery systems to promote cell survival in vitro and in vivo. A special
aspect of these studies is the combination therapies with combined drug delivery
systems to achieve local drug release, promote three-dimensional environment
to cells including islets.
New candidate drugs for therapeutic interventions in diabetes (including diabetic
neuropathy) require the development of novel delivery systems that are efficient,
practical, and economical. The delivery systems her group has been studying
are aimed at overcoming problems presented by the administration of currently
expensive or difficult to obtain compounds. Such an example is Islet Neogenesis
Associated Protein (Ingap). Recent findings show that a pentadecapeptide of
this protein is biologically active, and it is currently in clinical trials.
At this time there is a critical need for an improved drug delivery system
for this agent. Nonviral, biocompatible drug delivery systems, effective and
associated with the minimal adverse reactions are in focus of her team and
the collaborators in Chemistry department (Dr. Eisenberg's group) and polymer
scientists from University of Montreal headed by dr. JC Laroux and dr. F.Winnik.
Special contribution of Dr. Maysinger's team to the aims of the program will
be to develop a means of delivering agents that will promote islet cells,
or progenitor cells that will transform into islet cells, in a way that allows
those cells to secrete survive and function normally.
Currently, the laboratory efforts are focused on novel nano-delivery
systems and studying the effects of Ingap peptide in vitro and in vivo. These
investigations imply fluorescent labeled Ingap peptide, and investigations
of the cellular interactions between the peptide and cell proteins. The experiments
are expected to uncover the signal transduction molecules involved in islet
neogenesis as well as the promotion of peripheral outgrowth of nerves threatened
by the long term diabetes.
