• $9.6M Grant Targets Sickle Cell-Related Organ Damage

    Research from new Center of Excellence could add decades to lives by preventing kidney, heart damage

    The deadliest thing about sickle cell disease isn’t just the misshapen red blood cells it produces to cause vascular occlusions. A serious threat appears to come from oxidative stress, scientists are discovering. 

    Recent research has revealed that sickle cell disease changes the way reactive oxygen species (ROS) interact with the system that regulates blood pressure and fluids in the body, the renin angiotensin system. Over time, the activity of this harmful molecular pathway gradually destroys kidney and heart function.

    Five divisions at Cincinnati Children’s are now teaming up to study how to control this process. They will use a five-year, $9.6 million grant from the National Heart, Lung and Blood Institute (NHLBI) to create the Cincinnati Center of Excellence in Hemoglobinopathy. It is one of nine cooperative projects nationwide delving into promising lines of research in hemoglobin disorders.

    “We found that the same renin angiotensin system that causes renal damage in diabetes and hypertension also is activated by sickle cell,” says Punam Malik, MD, a researcher in Experimental Hematology and principal investigator for the new grant. “More importantly, we found that blocking this signaling pathway in mouse models prevents organ damage when they are transplanted with sickle cell disease.”

    An interdisciplinary team composed of scientists from the Heart Institute, the Cancer and Blood Disease Institute, and the Divisions of Experimental Hematology, Hematology, Radiology and Developmental Biology will explore how this signaling pathway can be manipulated in mouse models and whether a similar pathway exists and can be controlled in humans with sickle cell disease. The team also will explore novel non-invasive imaging tools to detect the earliest signs of cardiac damage in people with sickle cell disease.

  • Scientists Participating in the Grant

    Principal Investigator

    Punam Malik, MD

    Co-principal investigators

    Punam Malik, MD, Experimental Hematology and Hematology; Jeffrey Towbin, MD, Cardiology; Jay Degen, PhD, Experimental Hematology; and Charles Quinn, MD, Hematology.

    Co-investigators

    Theodosia Kalfa, MD, PhD, Hematology; Michael Taylor, MD, Cardiology; Steven Potter PhD, Developmental Biology; and Robert Fleck, MD, Radiology.

    Translational Scholars

    Omar Niss, MD, Hematology; and Paritha Arumugam, PhD, Experimental Hematology.

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