As project leader, Dr. Bruno Doiron has made major discoveries in the field of gene regulation by nutrients and has four patents on the modulation of glucose metabolism as it relates to the treatment
diabetes and cancer. He has extensive
experience in basic research at the physiologic and molecular levels and then
application to the biotechnology field.
recently, he has developed a method in vivo to target specifically adult
pancreas with viral vector that will be used in our program of research
Cellular Networking Integration Processing (CNIP) to induce beta cell
formation. The CNIP approach has the
advantage of its simplicity of application to induce pancreatic beta cell
formation specifically to the own pancreas of the diabetic subject. The use of
stem cells as a source of beta cell has received recent interest.
approach requires an in vitro culture
system with subsequent islets cell transplantation with all of the problems
that have limited this approach. The CNIP bypasses the problems associated with
in vitro petri dish culture, i.e.
good manufacturing practice, and the problems associated with islet
transplantation that have limited this approach for more than two decades. Stem
cells are highly proliferative and can readily form teratocarcinomas.
many of the transcriptional factors employed in stem cell transformation include
oncogenes like MafA. The in vitro stem cell differentiation protocols
do not produce a consistent level of beta cell-like differentiation for each
petri dish culture, and the beta-cell-like differentiated stem cells can
continue to differentiate into other cell types after injection in vivo, resulting in cell with a very
different profile than was present in the petri dish.
Thus, the in vitro cell
culture differentiation approach to form beta cells is far from clinical
application. Moreover, after the stem
cells are injected in vivo, one still has to deal with all of the hurdles
encountered in islet transplantation including the immune rejection process.
vivo CNIP approach obviates these hurdles.
The successful completion of this CNIP research program would have
an enormous impact on the treatment of type 1 diabetes and type 2 diabetes,
where one of the major physiopathologic mechanisms is the progressive loss of
pancreatic beta cells.
This research program could open the way for prevention,
treatment, and potentially a cure for this common metabolic disease that
affects 27 million individuals in the U.S. alone.
Doiron B, DeFronzo RA. Distinct Efffects of Metformin on Pdx-1 Before and After Birth. International Journal of Endocrinology Metabolism. 2011 Dec;9(2):356-357.