The Alam Laboratory
Faculty >Tausif Alam
Tausif Alam
Associate Scientist, Surgery Department, Division of Transplantation
Organ System/Disease Focus: Type I diabetes
Aligned Research Focus: Development of pluripotent stem cell-derived hepatocytes engineered to provide appropriate amounts of insulin to correct hyperglycemia.
Research Description
An increasing prevalence of type 1 diabetes combined with a severe shortage of donor organs for transplantation necessitates exploration into alternative sources of glucose-regulated in vivo insulin production to correct hyperglycemia. Liver cells are an attractive target for insulin gene expression. We have designed insulin expression constructs that cause insulin synthesis and secretion from transfected hepatocytes. The amount of secreted insulin is modulated in response to alterations in glucose levels. When diabetic animals are treated with such insulin constructs, their fasting hyperglycemia is fully corrected and the pattern of untreated diabetes-induced weight loss is reversed to normal rate of weight gain. We intend to develop and optimize methods using iPS cells of autologous derivation and differentiate them into hepatocytes to serve as host cells for insulin production in vivo. This strategy is likely to allow a cell-based therapy for type 1 diabetes without the use of immunosuppressive agents and it could be of general interest in treating other diseases involving liver or where autologous liver cells may be used as surrogate cells to produce other gene products of interest.
Selected References
Alam T, Sollinger HW. Glucose-regulated insulin production in hepatocytes. Transplantation. 2002;74(12):1781-7.
Nett P, Sollinger HW, Alam T. Hepatic insulin gene therapy in insulin dependent diabetes mellitus. Amer J Transplantation. 2003;3(10):1197-1203.
Ludwig S, Sollinger HW, Alam T. Can gene therapy make pancreas and islet transplantation obsolete? Curr Opin Organ Transplant. 2006;11:94-100.
Alam T, Sollinger, HW. Insulin gene therapy. Pancreas, islet, and stem cell transplantation for diabetes. Oxford University Press. 2010, 317-329.