O'Rourke Lab

The O'Rourke Lab, led by Dr. Robert W. O'Rourke, is progressing toward novel adipose-tissue-based therapies in metabolic disease.

Current Research in the O'Rourke Lab

Many diseases, including type 2 diabetes, cancer and hyperlipidemia, have been linked to obesity. The O'Rourke Laboratory, led by Dr. Robert W. O'Rourke, focuses on understanding the role adipose (fat) tissue plays in the development of obesity-related systemic metabolic diseases as well as cancer. Our research spans basic science and translational investigations closely aligned with Dr. O'Rourke's surgical practice treating patients with obesity—many of whom suffer from metabolic and inflammation-related disease.

The Problem

Over one-third of the U.S. population is obese, and obesity raises the risk of diabetes, cancer and other diseases. Bariatric surgery helps many patients lose weight, maintain weight loss and prevent or improve metabolic conditions, but novel non-surgical therapies for diabetes and other obesity-related metabolic diseases are a critical need.

Adipose tissue metabolic dysfunction is a key contributor to obesity-related disease pathogenesis. We are working to identify mechanisms underlying adipose tissue dysfunction to develop novel personalized adipose tissue-based therapy for obesity and associated metabolic diseases.

The Approach

The O'Rourke Research Laboratory has identified a number of mechanisms and pathways involved in adipose tissue dysfunction, inflammation and metabolic disease. These involve macrophages and natural killer (NK) immune cells as well as the extracellular matrix, the supporting environment around cells. We are especially interested in how each of these cells and tissue components communicates adipocytes, the primary fat storage cells, within adipose tissue. We are also interested in the signaling mechanisms and pathways adipocytes and cancer cells use to communicate in the context of certain types of cancer.

Contributions to Science

The work in the O'Rourke Research Laboratory has provided new insights into the biology of adipose tissue and its role in systemic metabolic and inflammation-related diseases such as diabetes and cancer. We have elucidated the role of macrophages and natural killer (NK) immune cells in dysfunctional adipose tissue, a previously unanswered research question. Our work investigating extracellular matrix–cellular interactions has deepened our understanding of the signaling pathways that regulate many cellular functions of adipocytes, particularly those that impact how cells metabolize glucose. Our work on the role of inflammation has homed in on hypoxia and cell stress as a trigger of inflammatory processes in adipose tissue. Our work on pancreatic cancer–adipocyte interactions is leading the field to better understand of the role that adipose tissue plays in carcinogenesis.

Our laboratory has developed a human adipose tissue bank of visceral and subcutaneous tissue from obese humans undergoing bariatric surgery. We also have created sophisticated in vitro two-dimensional and three-dimensional human cell culture systems to investigate metabolic crosstalk and the ways in which adipose tissue dysfunction impacts systemic metabolism. Finally, we have developed novel murine adipocyte transplant models that permit study of the effects of adipocyte-based therapy on in vivo systemic metabolism.