Stem cells and progenitor cells have the remarkable ability to develop into different cell types. They offer the potential to provide a renewable source of replacement cells to treat diseases, conditions, and disabilities. We use molecular and cell biology, biochemical, and biophysical approaches to learn how these cells work. We are also particularly interested in the role of cytokines, proteins that trigger the initial development of stem and progenitor cells into different cell types. Our research allows us to build models of how these processes work.
One focus of our lab’s research is on the way in which a stem cell produces a red blood cell offspring. Erythropoietin, produced in the kidney, is the cytokine that regulates the daily production of 200 billion new red blood cells. These red blood cells are important because they carry oxygen from the lungs to tissues. In our lab we investigate many roles of erythropoietin such as the following:
- When oxygen levels are low, erythropoietin is triggered to increase red blood cell formation. As more red blood cells are formed, more oxygen can be moved from the lungs to tissues. This increases overall oxygen levels in the body.
- Erythropoietin stimulates endothelial cells to produce increased nitric oxide production; this regulates blood flow and contributes to increasing oxygen delivery. We relate this activity to a protective effect in a mouse model of heart ischemic injury (blocked blood flow).
- Erythropoietin can stimulate muscle progenitor cells to promote wound healing in a mouse model of skeletal muscle injury.
- In the brain, erythropoietin can stimulate the proliferation of neural progenitor cells and the survival of neurons to provide protection in mouse models of ischemic injury.
- Erythropoietin has metabolic activity that results in increased whole body oxygen consumption. Circulating erythropoietin produced in the body contributes to the regulation of fat mass and blood glucose levels. Mice with erythropoietin activity restricted to red blood cell production develop obesity and insulin resistance.
- Increased erythropoietin treatment, especially in obese mice, increases energy expenditure and activity, reduces food intake, and reduces fat mass. We examine the specific contributions of fat tissue response to erythropoietin in the regulation of metabolism. We also examine the specific contributions of hypothalamus response to erythropoietin in the regulation of food intake and energy expenditure.
Other studies in our lab focus on the activity of the globin gene family. Globin genes are components of hemoglobin, the molecule that carries oxygen. These genes make up 98 percent of the protein in red blood cells that transport oxygen in the bloodstream. In particular, we want to understand the changes in hemoglobin function observed in sickle cell disease and other diseases related to hemoglobin abnormalities.