Research Summary
JDRF Research project: Self assembly drug delivery systems
and islet transplantations to enhance their efficiency in vivo.
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. Lawrence Rosenberg. This multi-disciplinary
collaboration has proved synergistic in the area of translational
research in terms of efficiently obtaining the results of molecular
biological studies in human islets and applying them to diabetic
patients in the clinic. Key findings from Dr. Maysinger's research
include the following:
(1) Pancreatic islets are dying in the post-isolation period by
apoptosis and delayed necrosis .
(2) Early pharmacological intervention during the islet isolation
procedure can enhance islet survival .
(3) Combined therapeutic intervention is beneficial during and after
islet isolation, as well as during the post-transplantation period.
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
Dr. Maysinger's group has been studying are aimed at overcoming
problems presented by the administration of drugs that are currently
expensive or difficult to obtain. Dr. Maysinger's research includes
the study of nano-delivery systems and other drug and cell-delivery
systems that can promote cell survival in vitro and in vivo. She
has developed novel combination therapy strategies which combine
drug delivery systems together to achieve effective local drug release
and to enhance the three-dimensional environment of islet and other
cells.
Islet Neogenesis Associated Protein (Ingap) is
a particularly interesting candidate drug for the treatment of diabetes.
Recent findings show that a pentadecapeptide of this protein is
biologically active. Ingap is currently in clinical trials and there
is an urgent need for improved drug delivery systems for Ingap in
the clinic. Dr. Maysinger's research group is focused on studying
the effects of Ingap peptide in vitro and in vivo (in mouse and
dog models of diabetes), as well as on developing new methods of
delivering Ingap and other drugs to diabetic patients, which will
promote islet cells survival and normal secretory function, and/or
the survival of progenitor cells that will transform into functional
islet cells.
Nonviral, biocompatible drug delivery systems that
are effective and have minimal adverse reactions are being studied
in Dr. Maysinger's laboratory at McGill and are also the subject
of her collaborations with the following research groups:
" Dr. Eisenberg's group (Chemistry Department, University of
?)
" Dr. JC Laroux and Dr. F.Winnik (X Department, University
of ?)
" Dr. X (Ecole Polytechnic (Polymer Chemistry?), University
of Montreal.
Fluorescent-labeled Ingap peptide is being used to investigate the
cellular interactions between Ingap peptide and cell proteins involved
in signal transduction processes that are important in islet neogenesis
and peripheral nerve outgrowth in diabetic patients.
|