The O'Rourke Laboratory uses several strategies to deepen our understanding of adipose tissue biology and dysfunction in obesity, metabolic disease and cancer, including:
Clarifying the Role of the Extracellular Matrix (ECM)
The ECM is comprised of molecules that surround adipocytes and adipose tissue and regulate adipocyte cell metabolism. In diabetic individuals, our lab has demonstrated that adipose tissue is altered, and that the ECM contributes to adipocyte dysfunction with respect to glucose metabolism. Our work continues to better understand the mechanisms by which those impairments occur and to develop methods to manipulate the ECM to improve adipocyte, and systemic, metabolism.
Bioengineering Artificial Matrices as a Therapeutic Vehicle in Diabetes
In collaboration with bioengineers, we are developing artificial matrices, also called bioscaffolds, in which we can grow adipocytes. By manipulating the matrices, we can engineer healthier adipocytes that can be transplanted into mice with diabetes and obesity in effort to cure these diseases.
Defining Preadipocyte Subpopulations Within Human Adipose Tissue
In addition to studying matrix–adipocyte interactions, we also investigate the ways in which the ECM interacts with stem cells that give rise to adipocytes within adipose tissue. Currently, we use single cell RNA sequencing to define preadipocyte and macrophage subpopulations within human adipose tissue in diabetes. Our objective is to understand which types may confer a metabolic benefit or be detrimental.
We are developing novel methods to isolate, extract and manipulate these cells in vitro to understand how they function–and how we can make them healthier. Our objective with this work, too, is to develop tissue that can be used as a therapeutic vehicle to improve metabolic dysfunction.
Investigating Additional Cell–Cell and Cell–Matrix Interactions
Our laboratory conducts research into other cell types, including macrophages, several types of immune cells and endothelial cells. The aim of this work is to better understand how these cell types communicate with adipocytes and the extracellular matrix so that we can identify the regulating mechanisms and engineer healthier adipose tissue.
Studying Adipocyte—Cancer Crosstalk
Our lab, and others, have hypothesized that dysfunctional adipocytes and adipose tissue may contribute to the development and growth of pancreatic cancer. We are studying the crosstalk between pancreatic cancer cells and adipocytes in in vitro murine pancreatic cancer models.