The Smallest Part of the Big Picture

Sickle cell disease symptoms all begin with the red blood cell.

“Often, you have to understand the minute details before you can make sense of the bigger picture,” muses Jon Detterich, MD. This mentality fuels his research at Children’s Hospital Los Angeles, where he looks to the smallest component of human life, the cell, to understand the complex symptoms of sickle cell disease.

Affecting more than 80,000 individuals in the United States, sickle cell disease is a lifelong condition characterized by crescent-shaped, or sickled, red blood cells. Because of their abnormal shape, these cells can become stuck in blood vessels, blocking blood flow to muscles and organs. This, in turn, can cause a variety of symptoms and complications, ranging from episodes of extreme pain to pulmonary hypertension and stroke.

“The problem with sickle cell disease is that doctors can treat these secondary effects, but they aren’t getting to the root of the problem—the red blood cell,” notes Detterich, a pediatric cardiologist at CHLA, as well as an assistant professor of Clinical Pediatrics, Physiology and Biophysics at the Keck School of Medicine of University of Southern California (USC).

Detterich first began exploring the fundamental makeup of sickle cell disease in 2008. His initial research, funded by a Sickle Cell Scholar Award from the National Institutes of Health (NIH), examined the fluid dynamics and unique properties of transfused blood.

All sickle cell patients will undergo at least one blood transfusion during their treatment, making it essential to understand the relationship between transfused blood and blood vessels. After studying these interactions, Detterich then turned his focus to the red blood cell itself.

“I wanted to see exactly how the process of cell sickling is impacted by molecules in the bloodstream, specifically nitric oxide,” says Detterich. “Furthermore, how does the cell then act on the blood vessel?”

Nitric oxide (NO) controls vessel constriction and dilation—a process that regulates blood flow to various tissues in the body. Dysregulation of the process is harmful to the blood vessels, potentially triggering them to narrow and leading to complications in sickle cell patients.

While NO is usually released by the inner lining of the blood vessels, Detterich believes that red blood cells may also be able to release NO of their own, resulting in dysregulation of NO in the bloodstream. Detterich recently received funding from the NIH to study his hypothesis, which could lead to novel treatments.

“It’s important that we look to understand the very foundation of the disease in order to successfully manage the complications and develop new therapies,” says Detterich.