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 high levels of fat in the blood, or 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 one's risk of diabetes, cancer and other diseases. Bariatric surgery helps many patients lose weight, maintain weight loss and prevent or improve metabolic conditions. Still, despite high clinical efficacy, outcomes among patients vary greatly. The same holds true for less invasive weight loss interventions like diet and medication. Novel therapy for diabetes and other obesity-related metabolic diseases is therefore a critical need.

Our lab believes, and there is evidence to support, that adipose tissue is dysfunctional in the context of obesity. We are working to identify mechanisms underlying adipose tissue dysfunction so we can understand why bariatric surgery, and other interventions, help patients. We want to use that knowledge to tailor treatment approaches for patients and to develop novel preventive and therapeutic approaches. Our laboratory's ultimate goal is to develop novel personalized adipose-tissue-based therapies to offer their patients with obesity and related disease.

The Approach

The O'Rourke Research Laboratory has identified and continues to investigate 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, which is 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 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.