Courtesy of E. Rosado-Olivieri
Courtesy of Nadav Sharon, from Sharon et al., Cell, 2019
Our goal is to develop significant new treatments for diabetes. We aim to eliminate the present practice of regular blood checks and insulin injections, replacing them with insulin-producing cell transplants, specifically pancreatic beta cells that measure glucose levels and secrete just the right amount of insulin. Our approach is best characterized as applying developmental biology to understand and change the course of diabetes.
Courtesy of S. Tsai, A. Veres, A. Faust, and E. Sintov
The methods we have developed to make hundreds of millions of functional beta cells from human stem cells (ES or iPS cells) form the central theme for our research. In one instance, we study how to make all the islet endocrine cells, including alpha (glucagon-producing) and delta (somatostatin-producing) cells and produce islet-like clusters. These human stem cell-derived islet clusters are used both in vitro and in vivo for metabolic studies on islet function.
iPS cells derived from either Type 1 (juvenile) or Type 2 (adult onset) diabetics has made it possible to begin studies on the root cause(s) of diabetes. These stem cell islet clusters, derived using patient's blood, enable studies on diabetic islet biology and are also being used to understand the cellular and genetic basis of the autoimmune attack in Type 1 diabetes.
A third area focuses on genetic modification of the stem cells, the starting material for islet clusters. Here the goal is to gain more complete control of in vitro differentiation by altering genes that determine cell fates. These islet clusters are shared with several collaborating bioengineers to explore physical protection following transplantation. We also genetically alter the islet cells so as to blunt or avoid an immune attack.
The three complementary research areas of our lab are depicted in the diagram above.