Versiti - Prithu Sundd Is Developing a Treatment to Prevent Acute Chest Syndrome in Patients with Sickle Cell Disease

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Prithu Sundd Is Developing a Treatment to Prevent Acute Chest Syndrome in Patients with Sickle Cell Disease

Milwaukee — November 19, 2025

Prithu Sundd, PhD, senior investigator at the Versiti Blood Research Institute (VBRI), and his lab have received a second renewal of his National Institutes of Health (NIH) R01 grant, extending it from its eleventh year to its fifteenth. This $3 million grant renewal over the next four years allows Sundd and his team to continue their work in developing a treatment to prevent acute chest syndrome, which is a leading cause of death for patients with sickle cell disease.

Sickle cell disease is one of the most common genetic blood disorders affecting African Americans, which causes red blood cells that are normally soft and round, to become stiff and change into a sickle or crescent shape. These malformed red blood cells tend to interrupt the body’s oxygen and blood flow by causing blockades in blood vessels, and patients with sickle cell disease contend with symptoms like organ damage, anemia, fatigue, recurrent pain, and acute chest syndrome (ACS). ACS happens when the blood flow is obstructed in the lungs, which sets off a domino effect of health complications, such as difficulty breathing, fever, and chest pain.

“The current therapy for acute chest syndrome in patients with sickle cell disease is only supportive, and an effective targeted therapy does not exist,” Sundd says. “The findings of this study will suggest for the first time that acute therapy of blocking STING-signaling in platelets may provide significant protection from the development of acute chest syndrome in sickle cell disease patients.”

In the Sundd lab’s earlier work on ACS, they discovered a new way that neutrophils (white blood cells that play a crucial role in the body’s immune system) are triggered to shed their DNA into web-like structures called neutrophil extracellular traps (NETs). NETs are normally a beneficial part of the body’s immune defense, but NETs also contribute to blood vessel injury and the formation of small clots (thrombi) in the lungs, which can trigger ACS.

With this grant renewal, Dr. Sundd’s lab will continue the work they have been doing over the last decade, specifically exploring how crosstalk between neutrophils and platelets in the blood of sickle cell patients leads to the overproduction of NETs, lung thrombosis, and the development of ACS. “These findings will inspire the development of efficient small molecule inhibitors of the STING pathway, and clinical trials to test whether the STING inhibitors can prevent development of ACS in high-risk SCD patients admitted to the emergency department with acute pain episodes,” says Sundd. Ultimately, the hope is that this research will lead to better treatment options for patients living with sickle cell disease.

Sundd notes that this grant and research work is a true example of the collaboration that can only happen at a place like Versiti. “The collaboration and teamwork of VBRI, MCW/Froedtert Adult Sickle Cell clinic, and the efforts of the Versiti Clinical Trials Research Office, along with new resources available at Versiti on King and the inception of an MCW Sickle Bio Bank, provide all the necessary resources to enable a high-impact translational research project like the current study,” Sundd says. “A collaborative team effort on such scale is hard to envision anywhere else in this country.”

Integral to the grant's success were collaborators Josh Field, MD, MS, and Tirthadipa Pradhan-Sundd, PhD; research scientist Tomasz Kaminski, PhD; research technician Nicholas Swendrowski; CTRO coordinator Shane Howe; and Katherine Kober at the VBRI Office of Sponsored Programs. This grant (Pulmonary arteriole occlusion by platelet-neutrophil micro-emboli in Acute Chest Syndrome), funded by the National Heart, Lung, and Blood Institute, was first awarded to Dr. Sundd in 2015, competitively renewed in 2021, and now it has been renewed again (2025-2029) based on the accomplishments over the last decade. Continuous grant renewals like this one are highly competitive and underscore the NIH’s trust in the excellence of VBRI’s research and our mission to transform today’s discoveries into tomorrow’s life-saving therapies.

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