Charlie Alpers, MD (Pathology)
Our research involves studies of kidney disease consequent to immune responses to foreign pathogens and as a consequence of diabetes.
Karol Bomsztyk, MD (Medicine/Allergy and Infectious Diseases)
Understanding the processes that signal gene expression is critically important for using stem cells in the treatment of disease. These intracellular processes include many factors that are organized into signaling cascades that regulate genes in the chromatin environment, or the epigenome. To better define these mechanisms our laboratory has been developing advanced epigenetic technologies and computational tools. Our and other member laboratories of the UW Medicine Institute for Stem Cell and Regenerative Medicine are already using these methods to better understand and treat cancer, diabetes, kidney, heart and other diseases where stem cell biology holds great promises.
Karin Bornfeldt, PhD (Metabolism, Endocrinology and Nutrition)
The goal of the Bornfeldt laboratory is to increase our understanding of the mechanisms causing cardiovascular complications of diabetes and the metabolic syndrome, and to find novel treatment strategies to combat these complications in patients. In relation to this overall goal, we are investigating the effects of diabetes and metabolic syndrome on hematopoietic stem cells in mechanistic mouse models. Another project in the lab, conducted in collaboration with Dr. Charles Murry, is focused on the effect of diabetes on myocardial infarction in mouse models and potential repair by stem cell-mediated approaches. Finally, Dr. Bornfeldt directs a Diabetes Research Center core facility (https://depts.washington.edu/diabetes/vtmc) together with Dr. Dan Miller. This core provides CRISPR services in stem cells in collaboration with ISCRM.
Vincenzo Cirulli, MD, PhD (Medicine/Metabolism, Endocrinology & Nutrition; Pharmacology)
The overall objective of Dr. Cirulli's research work is to understand mechanisms that foster the development and function of pancreatic islets of Langerhans, small clusters of 2,000-3,000 cells scattered throughout the pancreas, that are responsible for the production of such hormones as insulin, glucagon, somatostatin, and pancreatic polypeptide. Special attention in his laboratory is devoted to insulin-producing cells (also known as β-cells) whose function is lost in both type 1 and type 2 diabetes. The specific focus of Dr. Cirulli's research program is to understand the function of highly specialized proteins that regulate cell-cell and cell-matrix interactions in the pancreas. His previous work has established that 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 cells to decide whether to grow (i.e. increase in numbers) or to differentiate (i.e. mature) into functional adult cells.
Laura Crisa, MD, PhD (Medicine/Metabolism, Endocrinology and Nutrition)
Our research focuses on characterizing immune cells and vascular cell components that favor pancreatic tissue engraftment at transplantation sites. Specifically, we are interested in identifying survival, proliferative and or maturation signals that vascular cells and leukocytes may deliver to pancreatic islet cells or their progenitors. Knowledge gained from this research may help to define the best possible transplant microenvironment supporting engraftment of islet tissue and possibly unveil novel cellular signals that can influence the maturational program of pancreatic islet progenitors. This line of studies has a direct impact on islet cell replacement strategies as treatment for patients with Type 1 diabetes.
Cecilia Giachelli, PhD (Bioengineering)
My lab is interested in applying stem cell and regenerative medicine strategies to the areas of ectopic calcification, tissue engineering, biomaterials development and biocompatibility.
Jay W. Heinecke, MD (Medicine/Metabolism, Endocrinology & Nutrition)
Research in the Heinecke laboratory focuses on understanding the role of macrophages in the pathogenesis of atherosclerosis, obesity, and insulin resistance. Major efforts focus on using a proteomics approach to identify specific proteins targeted for posttranslational modifications and building a systems biology view of the macrophage. Current studies include: (1) Investigating oxidative pathways that regulate the activities of high-density lipoprotein (HDL) and matrix metalloproteinases (MMPs), which are of central importance in atherosclerosis; (2) Use of animals with genetically engineered deficiencies to understand the role of oxidants and proteases in the pathogenesis of vascular disease and obesity; (3) Identifying macrophage protein networks involved in atherogenesis; and (4) Translational studies exploring the links between the HDL proteome, the macrophage proteome, and susceptibility to cardiovascular disease.
Anne Hocking, PhD (Surgery)
The two objectives of our laboratory are: 1) to determine the impact of the diabetic metabolic environment of high glucose and fatty acids on MSC regulation of the local cellular responses to injury; and 2) to determining whether therapeutically administered MSCs reduce hypertrophic scarring by releasing soluble factors that regulate fibroproliferative responses to cutaneous injury.
Gerald Nepom, MD, PhD (Immunology; Director, Benaroya Research Institute; Director, Immune Tolerance Network)
For more than 25 years, I have focused on human immunology research, contributing to our understanding of HLA and autoimmune disease, integrating genetics with function, and engaging in translational initiatives to bridge laboratory and clinical immunology programs.
Michael W. Schwartz, MD (Medicine/Metabolism, Endocrinology and Nutrition)
Through a multi-institutional collaborative effort we have recently created the Diabetes-Stem Cell Program (DSCP) whose overarching goal is to unite expertise in stem cell biology with that in developmental biology of pancreatic beta cells, basic and clinical aspects of diabetes, implantation biology, and immunology in a joint scientific endeavor. Key objectives of the DSCP include not only the creation and commercialization of a new, cell-based method for diabetes treatment, but also the development of strategies to eliminate the risk of tumor formation in cell implants, and to optimize methods for cell differentiation and metabolic analysis.
Ian Sweet, PhD (Medicine/Metabolism, Endocrinology and Nutrition)
The production of insulin-producing cells from stem cells is an area of intense investigation due to its potential for facilitating transplantation of this tissue into diabetics. A major issue in this area is to determine what characteristics define a beta cell such that one can prove that one has truly created a surrogate.
Thomas N. Wight, PhD (Benaroya Research Institute)
This investigator leads a research program focused on the role that the extracellular matrix molecules, proteoglycans and hyaluronan, play in regulating vascular cell type and the regulation of extracellular matrix assembly. These pathways are fundamental to understanding the growth of new blood vessels in different tissues of the body, and have potential for direct tissue regeneration applications through the use of proteoglycan genes to bioengineer vascular tissue.