The grant will fund research into the impact of transfusions in patients with sickle cell disease and how to improve transfusion management for those with the disorder

NEW YORK – The National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) has awarded a five-year grant of $15.6 million to Karina Yazdanbakhsh, PhD, of New York Blood Center’s Lindsley F. Kimball Research Institute (LFKRI), to lead a collaborative research program studying the consequences of transfusions in patients with sickle cell disease and developing strategies to optimize transfusion management for this patient group.

 Drs. Hui Zhong, Xiuli An, Avital Mendelson, Cheryl Lobo, Francesca Vinchi and Karina Yazdanbakhsh of LFKRI and NYBCe

Photo taken outside NHLBI offices where team presented proposed program projects. (L to R): Drs. Hui Zhong, Xiuli An, Avital Mendelson, Cheryl Lobo, Francesca Vinchi and Karina Yazdanbakhsh (Not Pictured: Dr. Patricia Shi)

Sickle cell disease is an inherited red cell disorder affecting an estimated 100,000 individuals in the U.S., mostly African Americans and American Hispanics. The disease affects millions worldwide, mainly people of African descent, but also people of Hispanic, South Asian, and Middle Eastern ancestry. It is caused by a single genetic mutation that affects the shape of the oxygen carrying red blood cells, making it difficult for the red blood cells to get through small blood vessels, clogging the blood flow, and cutting off oxygen delivery to the organs. Sickle red blood cells die early, causing shortage of red cells and anemia with some cells disintegrating in the circulation, releasing toxic forms of hemoglobin that can cause tissue injury. The shortage of oxygen delivery to the organs and chronic tissue injury can lead to serious complications, including stroke and irreversible organ damage. Studies led by LFKRI have found that the hemolytic stress resulting from the released hemoglobin and its byproducts can alter the behavior of major immune cell types as well as cells in the bone marrow, worsening the sickle cell complications. These same cell types are impacted by transfusions, a lifesaving treatment for patients with sickle cell disease.

“The grant provides us with a unique opportunity to understand at the molecular level how transfusions can switch these key immune cells and bone marrow cells to function normally and to discover new transfusion protocols and combination therapies to reverse the hemolytic insult in sickle cell disease,” says Dr. Yazdanbakhsh. Transfusions decrease the risk of stroke in sickle cell disease by 90%. However, many indications for transfusion in sickle cell disease remain controversial partly due to our limited understanding of the complex biological processes that lead to disease complications in sickle cell disease despite the common single mutation and in part because of paucity of data on how transfusions improve or prevent sickle cell complications. The Program Project aims to fill these gaps in our knowledge to advance our understanding of transfusion outcomes, focusing on the role of hemolysis, with the goal to develop novel approaches to improve transfusion efficacy for this patient population.

“This hypothesis-driven approach to develop optimal transfusion management strategies to care for patients with sickle cell disease marries the capabilities of our outstanding basic science team with New York Blood Center’s core expertise as innovators and leaders in transfusion medicine practice,” said Christopher Hillyer, MD, President and CEO. “We are proud of Dr. Yazdanbakhsh’s outstanding work in the field and look forward to what she and her team will accomplish with this much-deserved research grant.”

The grant supports a multi-disciplinary research team, all from LFKRI, with Project Leads Drs. Xiuli An, Cheryl Lobo, Patricia Shi, and Francesca Vinchi and Co-Investigators Drs. Avital Mendelson and Hui Zhong. With expertise in stem cell biology, transfusion immunology, infectious disease, and clinical translation, the group will probe the processes responsible for the beneficial and harmful effects of transfusions in patients with sickle cell disease. The team is joined by sickle cell disease clinical experts, Drs. Deepa Manwani and Caterina Minniti, who will lead the clinical team at the Montefiore Heath Center for patient selection and recruitment. Focusing on key immune cells and cells in the bone marrow, the investigators will examine the impact of sickle cell associated hemolysis on transfusion outcome ranging from transfusion reactions and infections to lung injury and hematopoietic transplant outcomes. These studies will lay the foundation to optimize transfusion therapy protocols and provide highly needed guidance on expansion or restriction of indications for transfusion for sickle cell patients.

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