Tausif Alam, PhD
Position title: Senior Scientist, Surgery / 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.
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 using viral vectors, such as lentivirus and adeno-associated virus, their hyperglycemia is fully corrected and effects or poorly controlled hyperglycemia or untreated diabetes, such as hyperlipidemia and weight loss are restored to normal. 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.
- Handorf A, Sollinger H, Alam T. Long-term correction of diabetic hyperglycemia through glucose- responsive hepatic insulin production using lentivirus. Journal of Diabetology and Endocrinology. 2017;2(1):1-10. doi: 10.14312/2398-0281.2017-1.
- Alam T, Wai P, Held D, Vakili ST, Forsberg E, Sollinger H. Correction of diabetic hyperglycemia and amelioration of metabolic anomalies by minicircle DNA mediated glucose-dependent hepatic insulin production. PLoS ONE 2013;8(6):e67515.
- Alam T, Sollinger, HW. Insulin gene therapy. Pancreas, islet, and stem cell transplantation for diabetes.Oxford University Press. 2010, 317-329.
- Alam T, Sollinger HW. Glucose-regulated insulin production in hepatocytes. 2002;74(12):1781-7.