Led by Dr. Katherine A. Gallagher, the Gallagher Laboratory investigates the role of immunity, inflammation and epigenetics in wound healing, commonly in the setting of diabetes. She is a foremost authority in this translational area, working to advance our understanding of the basic mechanisms, pathways and proteins involved in regulating inflammation in wounds. The goal of this work, motivated in part by Dr. Gallagher's active vascular surgery clinical practice, is to identify new drug targets and therapies to improve wound healing in patients with diabetes and peripheral artery disease (PAD). Recently, her lab has expanded on these common themes and are examining the role of the immune system and epigenetics in aortic aneurysm formation.
Wounds such as diabetic foot ulcers are a major contributor to the high, and rising, financial impact of diabetes. Wounds that won't heal are the most common reason patients with diabetes are hospitalized, and they are also the top reason for leg, foot or toe amputation in the United States.
About 80,000 amputations due to nonhealing diabetic wounds take place each year in this country, with a high three-year mortality rate -- between 20% and 50%. Although we have made important strides in how we treat diabetes, we have yet to make significant inroads when it comes to secondary implications such as wound healing. While impaired healing has been associated with the state of chronic inflammation that often exists in diabetes, no effective therapeutic approach yet has been identified to repair the disordered healing processes in diabetic wounds.
The result is that, to date, we as clinicians have lacked effective options to offer our patients. The goal of the work in our laboratory is to remedy that – to understand how healing processes are impaired in diabetes, identify therapeutic targets and develop effective new approaches so that we can better treat our diabetic patients. Similar to the chronic inflammation seen in diabetic wounds, aortic aneurysm are a leading cause of cardiovascular death and one mechanism for aneurysm development in chronic inflammation secondary to impaired immune cells.
Our laboratory investigates the role chronic inflammation and immune cell function play in non-healing wounds and aortic aneurysm. The dysfunctional wound healing we see in the setting of diabetes is most likely caused by many factors, including changes in the tissue near the wound as well as, our work has revealed, systemic changes in the bone marrow. Stem cells from the bone marrow give rise to the immune cells linked to chronic inflammation.
Our lab is focused on identifying these changes at the molecular level so that we can understand precisely how wound healing systems are impaired in diabetes and other vascular conditions. This will enable us to develop new and targeted immune therapies to restore the normal cascade of wound healing and decrease AAA development.
Contributions to Science
Research conducted in the Gallagher Laboratory has led to several key contributions to the understanding of impaired wound healing in diabetes and the role of stem cells that are epigenetically programmed towards increased inflammation in diabetes.
Our group looked at the characteristics of macrophages involved in both inflammation and healing and showed how they differ in diabetic wounds. We also were the first to show that epigenetic changes — changes in how genes are expressed that are not caused by a change in the DNA sequence — in bone marrow stem cells lead certain wound macrophages to assume inflammatory rather than reparative states. These changes result in chronic inflammation that impedes healing.
We further identified several enzymes and pathways involved, pointing us to new targets for more effective therapeutic approaches. This work led us to look at other processes regulated by these enzymes and to begin investigations into an agent, already approved by the U.S. Food and Drug Administration for other conditions, to treat nonhealing diabetic wounds.