Versiti Blood Research Institute Articles

Understanding the Role of the Liver in Sickle Cell Disease

February 23, 2024

Associate Investigator Tirthadipa Pradhan-Sundd, PhD, studies the mechanisms behind hematological diseases and how to improve patient outcomes.

Versiti Blood Research Institute (VBRI) Associate Investigator Tirthadipa Pradhan-Sundd, PhD, has always been interested in learning new things. Her curiosity drove her to the field of science, where she delved deep into genetics and signaling pathways, studying the molecules that attach to cell receptors and initiate subsequent processes. She decided to investigate the mechanisms of these signaling pathways in hematologcial diseases as directed by the research. “In my lab, we are specially focusing on understanding the molecule mechanism behind hematological disorders such as sickle cell disease, blood lesions and hemophilia.”

Dr. Pradhan-Sundd’s knowledge of signaling pathways and liver functionality led her to explore sickle cell disease (SCD). In SCD, due to a single point mutation in the β-globin of hemoglobin , red blood cells become sickle shaped, undergoes hemolysis causing hemoglobin, heme and iron release in the bloodstream. This can lead to serious health issues, including debilitating pain, vasoocclusive crisis, inflammation, stroke and end organ damage. To combat this, many patients receive frequent blood transfusions that ease their symptoms but overtime can led to iron buildup throughout the body. “Over time, the liver functionality is reduced, and this has been shown to be associated with increased mortality,” she said. “Our research focuses on combatting organ injury and mortality associated with this disease.”

Understanding how to clear iron buildup in the body is key in preventing organ damage in SCD patients. Researchers have long understood that hemoglobin can be cleared from the liver and spleen via macrophages, a type of white blood cell. Recently, Dr. Pradhan-Sundd’s lab discovered that endothelial cells, the cells that line blood vessels, also play an important role in hemoglobin clearance in the bloodstream. “This opens up a new area of research,” she said. “Our main focus is to look at the function of how the liver clears hemoglobin-heme- iron in sickle cell disease and other relevant hematological disorders.”

To accomplish this, Dr. Pradhan-Sundd plans to obtain biopsied liver samples from patients with various levels of iron accumulation. Her goal is to identify biomarkers for chronic organ injury and hemoglobin buildup related to blood transfusions, as well as receptors for endothelial cell-driven hemoglobin clearance. “The aim is to understand how iron accumulation builds up over time and how it affects the liver,” she said, “and find a bench-to-bedside connection.”

Identifying these biomarkers will help Dr. Pradhan-Sundd and her team develop a treatment to improve the liver’s regeneration capacity. This would enable SCD patients to continue to receive blood transfusions without the risk of iron building up in their bodies and may also help other organs affected by the disease. “We are still far away from a complete cure for all SCD patients,” she said, “but we are getting closer to the root of the issue.

About the expert: Tirthadipa Pradhan-Sundd, PhD, is an associate investigator at Versiti Blood Research Institute and an assistant professor in the Department of Cell Biology, Neurobiology and Anatomy, and Division of Hematology and Oncology at the Medical College of Wisconsin.