Vincenzo Cirulli, MD, PhD (Metabolism, Endocrinology & Nutrition)
The overall objective of our team is to study mechanisms that regulate the development and function of a specialized type of pancreatic cells, known as β-cells, that are responsible for the production of insulin, and whose function is lost in type 1 diabetes, or altered in type 2 diabetes. A major area of focus in the lab is to understand the function of proteins that regulate cell-cell and cell-matrix interactions in the pancreas. These proteins, also referred to as “cell adhesion molecules,” are used by cells not only to aggregate with each other, but also to let cells talk to one another through the exchange of biochemical signals, thereby helping developing/immature cells to decide whether to grow (i.e. increase in numbers) or to differentiate (i.e. mature) into functional adult β-cells. In an effort to develop strategies of possible translational value to human diabetes, our team is using a multipronged approach. On the one hand, we are trying to understand if tissue donor-derived immature pancreatic cells can be coaxed to produce insulin upon stimulation with molecules that foster cell-cell and/or cell-matrix interactions. On the other hand, recombinant cell adhesion molecules that we are producing in the lab are used as biochemical cues to test whether they can trigger the maturation of stem cells to become insulin-producing β-cells, or to trigger the proliferation of adult β-cells, thus increasing their number before transplantation, or promote their regeneration in diabetic patients.
Laura Crisa, MD, PhD (Metabolism, Endocrinology & Nutrition)
Our research aims to discover tissue regenerative signals provided by pro-repair immune cells and blood vessels. Our goal is to exploit these signals to boost regeneration of injured pancreatic islet cells in vivo, expand the rare pool of stem cell-derived islet progenitors and deliver those signals to transplant sites to support survival and function of pancreatic islet tissue. We are further working at modeling islet tissue as functional micro-organs in a dish, so to monitor how islet cells get injured and whether they can recover in response to regenerative interventions. This line of studies has a direct impact on islet cell replacement strategies as treatment for patients with Type 1 and Type 2 diabetes.
Cole DeForest, PhD (Chemical Engineering)
While the potential for biomaterial-based strategies to improve and extend the quality of human health through tissue regeneration and the treatment of disease continues to grow, the majority of current strategies rely on outdated technology initially developed and optimized for starkly different applications. Therefore, the DeForest Group seeks to integrate the governing principles of rational design with fundamental concepts from material science, synthetic chemistry, and stem cell biology to conceptualize, create, and exploit next-generation materials to address a variety of health-related problems. We are currently interested in the development of new classes of user-programmable hydrogels whose biochemical and biophysical properties can be tuned in time and space over a variety of scales. Our work relies heavily on the utilization of cytocompatible bioorthogonal chemistries, several of which can be initiated with light and thereby confined to specific sub-volumes of a sample. By recapitulating the dynamic nature of the native tissue through 4D control of the material properties, these synthetic environments are utilized to probe and better understand basic cell function as well as to engineer complex heterogeneous tissue.